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Sample records for lung carcinoma standardized

  1. Potential targets for lung squamous cell carcinoma

    Cancer.gov

    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

  2. Results of surgical therapy for lung carcinoma.

    PubMed

    Paris, F; Padilla, J; Tarazona, V; Blasco, E; Canto, A; Pastor, J; Zarza, A G

    1979-01-01

    A series of 300 pulmonary resections in patients with lung carcinoma is presented. Total survival rate of the series since the operation, including surgical mortality, was 33% at 3 years and 24% at 5 years. The survival rate and surgical criteria were correlated, having better results when standard surgery was performed. The authors emphasize that the surgical figures of the series are of great value as the surgical indications were large and nonselective, with 85% of resectability in the thoracotomies. PMID:229985

  3. Clear cell carcinoma of the lung.

    PubMed Central

    Edwards, C; Carlile, A

    1985-01-01

    Six tumours of the lung initially classified as clear cell carcinoma, were studied. Examination of further material by light and electron microscopy showed adenocarcinomatous differentiation in three cases and squamous differentiation in two. One case showed the features of a large cell anaplastic carcinoma. The clear appearance of the cytoplasm in paraffin sections was due to accumulations of glycogen that were partially removed during processing. It is concluded that clear cell carcinoma is not a single and separate entity. Images PMID:4031101

  4. Obstructive jaundice in small cell lung carcinoma.

    PubMed

    Mokhtar Pour, Ali; Masir, Noraidah; Isa, Mohd Rose

    2015-08-01

    Small cell lung carcinoma (SCLC) commonly metastasizes to distant organs. However, metastasis to the pancreas is not a common event. Moreover, obstructive jaundice as a first clinical presentation of SCLC is extremely unusual. This case reports a 51-year-old male with SCLC, manifesting with obstructive jaundice as the initial clinical presentation. Endoscopic retrograde cholangiopancreatograghy (ERCP) and abdominal computed tomography (CT) scan showed a mass at the head of the pancreas. The patient underwent pancreatoduodenectomy (Whipple procedure). Histopathology revealed a chromogranin- A-positive poorly-differentiated neuroendocrine carcinoma of the pancreas. No imaging study of the lung was performed before surgery. A few months later, a follow-up CT revealed unilateral lung nodules with ipsilateral hilar nodes. A lung biopsy was done and histopathology reported a TTF- 1-positive, chromogranin A-positive, small cell carcinoma of the lung. On review, the pancreatic tumour was also TTF-1-positive. He was then treated with combination chemotherapy (cisplatin, etoposide). These findings highlight that presentation of a mass at the head of pancreas could be a manifestation of a metastatic tumour from elsewhere such as the lung, and thorough investigations should be performed before metastases can be ruled out. PMID:26277673

  5. Carcinoma of the lung complicating lipoid pneumonia

    SciTech Connect

    Felson, B.; Ralaisomay, G.

    1983-11-01

    The authors have encountered four cases of oil aspiration pneumonia complicated by carcinoma. Each had a clear-cut history of chronic intake of an oily substance, radiographic changes, and histologically documented oil aspiration pneumonia. Lung cancer later appeared in the involved area. A small number of similar cases also have been reported. The implication is that oil aspiration pneumonitis may induce bronchogenic carcinoma, particularly either the alveolar cell or the squamous cell variety. The radiographic diagnosis of the malignant transformation is difficult, and consequently the prognosis is poor.

  6. A Rare Case of Pleomorphic Carcinoma of the Lung Harboring an Anaplastic Lymphoma Kinase (ALK) Rearrangement.

    PubMed

    Shiroyama, Takayuki; Tanaka, Ayako; Tamiya, Motohiro; Hamaguchi, Masanari; Osa, Akio; Takeoka, Sawa; Tani, Eriko; Azuma, Yuichiro; Morishita, Naoko; Suzuki, Hidekazu; Okamoto, Norio; Kimura, Kenji; Kadota, Yoshihisa; Kawahara, Kunimitsu; Hirashima, Tomonori; Kawase, Ichiro

    2015-01-01

    Molecular testing for anomalies, such as epidermal growth factor receptor mutations and anaplastic lymphoma kinase (ALK) rearrangement, is part of the current standard of care for non-small cell lung cancer, particularly adenocarcinoma. ALK rearrangement occurs most frequently in adenocarcinoma cells and rarely in non-adenocarcinoma cells. We herein report a rare case of pleomorphic lung carcinoma with ALK rearrangement in both its adenocarcinoma and spindle cell components. This case suggests the possibility of ALK rearrangement in pleomorphic carcinoma. PMID:26521903

  7. Ectopic ACTH Production in Carcinoma of the Lung

    PubMed Central

    Gewirtz, George; Yalow, Rosalyn S.

    1974-01-01

    Immunoreactive ACTH was found in almost all tissue extracts of lung carcinoma from patients without clinical evidence of Cushing's syndrome; i.e. 14 of 15 primary tumors, nine of nine metastatic lymph nodes, and four of four metastatic liver nodules contained immunoreactive ACTH. The incidence of ACTH in extracts of other tumor types was much lower. Comparable normal tissues contained no detectable ACTH. Immunoreactive growth hormone, parathyroid hormone, or gastrin was not found in the same carcinoma tissue. The predominant form of ACTH in the tumor extracts was big ACTH. In pituitary extracts little ACTH predominated. 53% of 83 patients with lung carcinoma had afternoon plasma ACTH levels greater than 150 pg/ml; more than 90% of plasmas containing less than 150 pg/ml were obtained from patients who had received radiation therapy or chemotherapy. 31% of 45 patients with chronic obstructive pulmonary disease (COPD), 28% of 25 patients with other severe lung disease, and 6% of 33 controls had elevated values. Big ACTH predominated in the plasma of patients with lung carcinoma or COPD having elevated ACTH levels. Tissue from the lung of a smoking dog with atypical histologic changes contained immunoreactive ACTH, almost exclusively in the big form, while tissue from another smoking dog that was histologically normal contained no ACTH. Thus ACTH may be present even in precancerous lung lesions. These studies suggest that serial plasma ACTH levels may be of value in screening for, and/or management of, patients with carcinoma of the lung. PMID:4360854

  8. Molecular profiling of lung adenosquamous carcinoma: hybrid or genuine type?

    PubMed Central

    Vassella, Erik; Langsch, Stephanie; Dettmer, Matthias S.; Schlup, Cornelia; Neuenschwander, Maja; Frattini, Milo; Gugger, Mathias; Schäfer, Stephan C.

    2015-01-01

    Lung adenosquamous carcinoma is a particular subtype of non-small cell lung carcinoma that is defined by the coexistence of adenocarcinoma and squamous cell carcinoma components. The aim of this study was to assess the mutational profile in each component of 16 adenosquamous carcinoma samples from a Caucasian population by a combination of next generation sequencing using the cancer hotspot panel as well as the colon and lung cancer panel and FISH. Identified mutations were confirmed by Sanger sequencing of DNA from cancer cells of each component collected by Laser Capture microdissection. Mutations typical for adenocarcinoma as well as squamous cell carcinoma were identified. Driver mutations were predominantly in the trunk suggesting a monoclonal origin of adenosquamous carcinoma. Most remarkably, EGFR mutations and mutations in the PI3K signaling pathway, which accounted for 30% and 25% of tumors respectively, were more prevalent while KRAS mutations were less prevalent than expected for a Caucasian population. Surprisingly, expression of classifier miR-205 was intermediate between that of classical adenocarcinoma and squamous cell carcinoma suggesting that adenosquamous carcinoma is a transitional stage between these tumor types. The high prevalence of therapy-relevant targets opens new options of therapeutic intervention for adenosquamous carcinoma patients. PMID:26068980

  9. Effects of dietary fat on spontaneous metastasis of Lewis lung carcinoma in mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The present study assessed the effects of dietary fat on spontaneous metastasis of Lewis lung carcinoma in mice. Three-week old male C57BL/6 mice were fed the AIN-93G standard diet or a 45% fat diet (kcal %) for seven weeks before they were subcutaneously injected with 2.5 x 105 viable cells into th...

  10. Pedunculated-type T1 colorectal carcinoma with lung carcinoma metastasis at the deepest invasive portion.

    PubMed

    Asayama, Naoki; Oka, Shiro; Tanaka, Shinji; Hirano, Daiki; Sumimoto, Kyoku; Ninomiya, Yuki; Tamaru, Yuzuru; Shigita, Kenjiro; Hayashi, Nana; Shimamoto, Fumio; Arihiro, Koji; Chayama, Kazuaki

    2016-08-01

    We present a rare case of colorectal T1 carcinoma with metastasis of previous lung carcinoma found at the deepest invasive portion. A 61-year-old man presented with cervical lymphadenopathy 18 years after undergoing surgery for right lung carcinoma [poorly differentiated adenocarcinoma stage IIb (T3N0M0)]. Contrast-enhanced computed tomography showed enlarged lymph nodes (LNs) in the neck and mediastinal regions. Combined hybrid-F-fluorodeoxyglucose positron emission-computerized tomography showed increased radionuclide uptake in multiple cervical LNs and mediastinal LNs. LN biopsy revealed a poorly differentiated adenocarcinoma, suspected to be a metastatic tumor of the lung. Subsequent colonoscopy revealed a pedunculated-type lesion with a depressed area in the ascending colon. We performed polypectomy as total excisional biopsy; this tumor was composed mainly of moderately differentiated adenocarcinoma, partially mixed with mucinous adenocarcinoma. The pathological findings of the invasive front of the colorectal carcinoma showed poorly differentiated adenocarcinoma with a morphological pattern similar to that of the previous lung carcinoma. Furthermore, immunohistochemical results for the histological type of the deepest invasive portion of the tissue specimen were positive for thyroid transcription factor-1 but negative for Caudal-type homeobox 2. From these morphological and immunohistochemical findings, the final diagnosis was moderately differentiated lung carcinoma, pTX N3 M1b (LN, colon) Stage IV. PMID:27259703

  11. An unsuspected diagnosis of mucoepidermoid carcinoma of lung.

    PubMed

    Al-Zamkan, Bassil; Sangani, Niravkumar; Jansen, Michael; Aljassim, Obaid

    2015-10-01

    A 40-year-old man with dry cough for 5 years, no history of smoking, and a right lung mass, underwent a radiologically-guided core needle biopsy. The initial histopathological diagnosis was adenocarcinoma of the lung. After lobectomy, the final pathology was mucoepidermoid carcinoma. The initial biopsies sampled only a mucinous component of the tumor, leading to a diagnosis of adenocarcinoma. The possibility of mucoepidermoid carcinoma could be suspected on the basis of clinical history and radiologic evidence. This unusual case highlights the importance of adequate multidisciplinary review of patients who increasingly receive pathologic diagnoses based on ever smaller tissue samples. PMID:25792546

  12. Chemoprevention of lung squamous cell carcinoma by ginseng.

    PubMed

    Pan, Jing; Zhang, Qi; Li, Kezhen; Liu, Qian; Wang, Yian; You, Ming

    2013-06-01

    Ginseng has been used as a medicinal herb to maintain physical vitality for thousands of years, and it has also been shown to be a nonorgan-specific cancer preventive agent by several epidemiologic studies. However, the chemopreventive effects of Korea white ginseng (KWG) in lung squamous cell carcinoma (SCC) have not been tested. In this study, we investigated the chemopreventive activity of KWG in a mouse lung SCC model. N-nitroso-trischloroethylurea (NTCU) was used to induce lung tumors in female Swiss mice, and KWG was given orally. KWG significantly reduced the percentage of lung SCCs from 26.5% in the control group to 9.1% in the KWG group and in the meantime, increased the percentage of normal bronchial and hyperplasia. KWG was also found to greatly reduce squamous cell lung tumor area from an average of 9.4% in control group to 1.5% in the KWG group. Treatment with KWG decreased Ki-67 staining, suggesting that the lung tumor inhibitory effects of KWG were partly through inhibition of proliferation. High-performance liquid chromatography/mass spectrometry identified 10 ginsenosides from KWG extracts, Rb1 and Rd being the most abundant as detected in mouse blood and lung tissue. The tumor inhibitory effects of KWG are mediated by inhibition of activator protein (AP-1), as showed by in vitro study conducted on AP-1/NF-κB-dependent mouse non-small cell lung carcinoma cell lines. Western blotting of lung tissues also indicated that NTCU upregulated AP-1 through phosphorylation of c-jun-NH2-kinase, which was downregulated by KWG in concurrence with its chemoprevention function. These results suggest that KWG could be a potential chemopreventive agent for lung SCC. PMID:23550152

  13. Genomic landscape of small cell carcinoma of the breast contrasted to small cell carcinoma of the lung.

    PubMed

    McCullar, Brennan; Pandey, Manjari; Yaghmour, George; Hare, Felicia; Patel, Kruti; Stein, Matthew; Feldman, Rebecca; Chandler, Jason C; Martin, Michael G

    2016-07-01

    Small cell carcinoma of the breast is a rare, aggressive form of breast cancer that is associated with extremely poor outcomes [1]. In an effort to identify possible targets for treatment, we utilized comprehensive genomic profiling in small cell carcinoma of the breast. Under an IRB approved protocol, we identified patients with small cell carcinoma of the breast and small cell carcinoma of the lung profiled by Caris Life Sciences between 2007 and 2015. Tumors were assessed with up to 25 immunohistochemical stains, in situ hybridization of cMET, EGFR, HER2, PIK3CA, and TOP2A, and next generation sequencing as well as Sanger sequencing of 47 genes. 19 patients with small cell carcinoma of the breast were identified, median age was 58 years (range 37-79) and 42 % had metastatic disease at presentation; for comparison, 58 patients with small cell carcinoma of the lung were identified (66 [36-86], 65 % metastatic). By immunohistochemistry, 31 % of small cell carcinoma of the breast patients expressed ER, 13 % expressed PR, and 16 % expressed AR; small cell carcinoma of the lung patients expressed ER 0 %, PR 2 %, and AR 6 %. Small cell carcinoma of the breast and small cell carcinoma of the lung patients had similar patterns of other immunohistochemical expression (0 v 0 % PDL1, 50 v 42 % PD1, and 77 v 95 % TOP2A, respectively). All small carcinoma of the breast and small cell carcinoma of the lung patients were negative for HER2 and cMET amplification by in situ hybridization. Next generation sequencing revealed TP53 mutations in 75 % of patients both with small cell carcinoma of the breast and small cell carcinoma of the lung and PIK3CA mutations in 33 % of small cell carcinoma of the breast patients but no small cell carcinoma of the lung patients (Fisher's exact test p = 0.005, OR 0.02 [0.00-0.52]). No other mutations were found in small cell carcinoma of the breast patients and no other mutation occurred in over 10 % of small cell carcinoma of the

  14. Identification of differentially expressed genes between lung adenocarcinoma and lung squamous cell carcinoma by gene expression profiling.

    PubMed

    Lu, Chaojing; Chen, Hezhong; Shan, Zhengxiang; Yang, Lixin

    2016-08-01

    The present study aimed to identify the differentially expressed genes (DEGs) between lung adenocarcinoma and normal lung tissues, and between lung squamous cell carcinoma and normal lung tissues, with the purpose of identifying potential biomarkers for the treatment of lung cancer. The gene expression profile (GSE6044) was downloaded from the Gene Expression Omnibus database, which included data from 10 lung adenocarcinoma samples, 10 lung squamous cell carcinoma samples, and five matched normal lung tissue samples. After data processing, DEGs were identified using the Student's t‑test adjusted via the Benjamini‑Hochberg method. Subsequently, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of the DEGs was performed using the Database for Annotation, Visualization and Integrated Discovery, and a global network was constructed. A total of 95 upregulated and 241 downregulated DEGs were detected in lung adenocarcinoma samples, and 204 upregulated and 285 downregulated DEGs were detected in lung squamous cell carcinoma samples, as compared with the normal lung tissue samples. The DEGs in the lung squamous cell carcinoma group were enriched in the following three pathways: Hsa04110, Cell cycle; hsa03030, DNA replication; and hsa03430, mismatch repair. However, the DEGs in the lung adenocarcinoma group were not significantly enriched in any specific pathway. Subsequently, a global network of lung cancer was constructed, which consisted of 341 genes and 1,569 edges, of which the top five genes were HSP90AA1, BCL2, CDK2, KIT and HDAC2. The expression trends of the above genes were different in lung adenocarcinoma and lung squamous cell carcinoma when compared with normal tissues. Therefore, these genes were suggested to be crucial genes for differentiating lung adenocarcinoma and lung squamous cell carcinoma. PMID:27356570

  15. Identification of differentially expressed genes between lung adenocarcinoma and lung squamous cell carcinoma by gene expression profiling

    PubMed Central

    Lu, Chaojing; Chen, Hezhong; Shan, Zhengxiang; Yang, Lixin

    2016-01-01

    The present study aimed to identify the differentially expressed genes (DEGs) between lung adenocarcinoma and normal lung tissues, and between lung squamous cell carcinoma and normal lung tissues, with the purpose of identifying potential biomarkers for the treatment of lung cancer. The gene expression profile (GSE6044) was downloaded from the Gene Expression Omnibus database, which included data from 10 lung adenocarcinoma samples, 10 lung squamous cell carcinoma samples, and five matched normal lung tissue samples. After data processing, DEGs were identified using the Student's t-test adjusted via the Benjamini-Hochberg method. Subsequently, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of the DEGs was performed using the Database for Annotation, Visualization and Integrated Discovery, and a global network was constructed. A total of 95 upregulated and 241 downregulated DEGs were detected in lung adenocarcinoma samples, and 204 upregulated and 285 downregulated DEGs were detected in lung squamous cell carcinoma samples, as compared with the normal lung tissue samples. The DEGs in the lung squamous cell carcinoma group were enriched in the following three pathways: Hsa04110, Cell cycle; hsa03030, DNA replication; and hsa03430, mismatch repair. However, the DEGs in the lung adenocarcinoma group were not significantly enriched in any specific pathway. Subsequently, a global network of lung cancer was constructed, which consisted of 341 genes and 1,569 edges, of which the top five genes were HSP90AA1, BCL2, CDK2, KIT and HDAC2. The expression trends of the above genes were different in lung adenocarcinoma and lung squamous cell carcinoma when compared with normal tissues. Therefore, these genes were suggested to be crucial genes for differentiating lung adenocarcinoma and lung squamous cell carcinoma. PMID:27356570

  16. Metastatic Lung Carcinoma Involving the Maxillary Gingiva.

    PubMed

    Sawheny, Eva; Khawar, Muhammad Umair; Ahmad, Shoaib; Jones, Kellie

    2016-01-01

    Metastatic spread of malignant tumors to the oral soft tissue is rare and account for 0.1% of all oral malignancies. Metastatic spread to the oral soft tissue can present as dental infections, which in turn can create a diagnostic challenge. Metastasis to the oral soft tissue from lung cancer is a rare situation. Here we describe a 52 year-old male patient treated initially with antibiotics for presumed oral abscess, who later was found to have metastatic lung cancer involving the maxillary gingiva. PMID:27027144

  17. Left Atrial Myxoma in a Late Case of Lung Carcinoma.

    PubMed

    Rahman, M M; Ranjan, R; Khan, O S; Aftabuddin, M; Hoque, M R

    2016-04-01

    Concomitant occurrence of lung carcinoma and an atrial myxoma is rare. We are reporting such a case, a 55 year old male, farmer, smoker for 30 years was under evaluation for his recent episode of stroke with hemiparesis during which an echocardiography showed presence of a left atrial myxoma and chest x-ray showed a lesion in the midzone of right lung. Fine needle aspiration cytology (FNAC) from enlarged right supraclavicular lymphnode revealed metastatic adenocarcinoma. Patient was referred to a tertiary cancer care hospital thereafter. PMID:27277375

  18. Standardized beam bouquets for lung IMRT planning

    NASA Astrophysics Data System (ADS)

    Yuan, Lulin; Wu, Q. Jackie; Yin, Fangfang; Li, Ying; Sheng, Yang; Kelsey, Christopher R.; Ge, Yaorong

    2015-02-01

    The selection of the incident angles of the treatment beams is a critical component of intensity modulated radiation therapy (IMRT) planning for lung cancer due to significant variations in tumor location, tumor size and patient anatomy. We investigate the feasibility of establishing a small set of standardized beam bouquets for planning. The set of beam bouquets were determined by learning the beam configuration features from 60 clinical lung IMRT plans designed by experienced planners. A k-medoids cluster analysis method was used to classify the beam configurations in the dataset. The appropriate number of clusters was determined by maximizing the value of average silhouette width of the classification. Once the number of clusters had been determined, the beam arrangements in each medoid of the clusters were designated as the standardized beam bouquet for the cluster. This standardized bouquet set was used to re-plan 20 cases randomly selected from the clinical database. The dosimetric quality of the plans using the beam bouquets was evaluated against the corresponding clinical plans by a paired t-test. The classification with six clusters has the largest average silhouette width value and hence would best represent the beam bouquet patterns in the dataset. The results shows that plans generated with a small number of standardized bouquets (e.g. 6) have comparable quality to that of clinical plans. These standardized beam configuration bouquets will potentially help improve plan efficiency and facilitate automated planning.

  19. Standardized beam bouquets for lung IMRT planning.

    PubMed

    Yuan, Lulin; Wu, Q Jackie; Yin, Fangfang; Li, Ying; Sheng, Yang; Kelsey, Christopher R; Ge, Yaorong

    2015-03-01

    The selection of the incident angles of the treatment beams is a critical component of intensity modulated radiation therapy (IMRT) planning for lung cancer due to significant variations in tumor location, tumor size and patient anatomy. We investigate the feasibility of establishing a small set of standardized beam bouquets for planning. The set of beam bouquets were determined by learning the beam configuration features from 60 clinical lung IMRT plans designed by experienced planners. A k-medoids cluster analysis method was used to classify the beam configurations in the dataset. The appropriate number of clusters was determined by maximizing the value of average silhouette width of the classification. Once the number of clusters had been determined, the beam arrangements in each medoid of the clusters were designated as the standardized beam bouquet for the cluster. This standardized bouquet set was used to re-plan 20 cases randomly selected from the clinical database. The dosimetric quality of the plans using the beam bouquets was evaluated against the corresponding clinical plans by a paired t-test. The classification with six clusters has the largest average silhouette width value and hence would best represent the beam bouquet patterns in the dataset. The results shows that plans generated with a small number of standardized bouquets (e.g. 6) have comparable quality to that of clinical plans. These standardized beam configuration bouquets will potentially help improve plan efficiency and facilitate automated planning. PMID:25658486

  20. Standardized beam bouquets for lung IMRT planning

    PubMed Central

    Yuan, Lulin; Wu, Q Jackie; Yin, Fangfang; Li, Ying; Sheng, Yang; Kelsey, Christopher R.; Ge, Yaorong

    2015-01-01

    The selection of the incident angles of the treatment beams is a critical component of IMRT planning for lung cancer due to significant variations in tumor location, tumor size and patient anatomy. We investigate the feasibility of establishing a small set of standardized beam bouquets for planning. The set of beam bouquets were determined by learning the beam configuration features from 60 clinical lung IMRT plans designed by experienced planners. A k-medoids cluster analysis method was used to classify the beam configurations in the dataset. The appropriate number of clusters was determined by maximizing the value of average silhouette width of the classification. Once the number of clusters had been determined, the beam arrangements in each medoid of the clusters were designated as the standardized beam bouquet for the cluster. This standardized bouquet set was used to re-plan 20 cases randomly selected from the clinical database. The dosimetric quality of the plans using the beam bouquets was evaluated against the corresponding clinical plans by a paired t-test. The classification with 6 clusters has the largest average silhouette width value and hence would best represent the beam bouquet patterns in the dataset. The results shows that plans generated with a small number of standardized bouquets (e.g. 6) have comparable quality to that of clinical plans. These standardized beam configuration bouquets will potentially help improve plan efficiency and facilitate automated planning. PMID:25658486

  1. Lung Metastasis of Renal Cell Carcinoma: ACase Report of Pulmonary Sarcomatoid Carcinoma.

    PubMed

    Fan, Tao; Song, Ying-Jie

    2016-06-01

    Pulmonary sarcomatoid carcinoma (PSC) is a rare malignant cancer composed of sarcoma and sarcoma-like elements with spindle or giant cell features. We report the case of a 60-year-old male with past medical history of right renal cell carcinoma 2 years earlier. Apulmonary nodule was detected in the left upper lobe, 23 months after nephrectomy. Systemic positron emission tomography-computerized tomography (PET-CT) revealed one high metabolic mass shadow in the left upper lobe. Chest CTscan with contrast revealed a left upper lobe mass (2.9 x 2.5 cm). The case was suspected to be a lung metastasis of renal cell carcinoma. After surgery, the pathology revealed PSC-giant cell carcinoma. The tumor's pathology and treatment methods are discussed. PMID:27376226

  2. Snail promotes an invasive phenotype in lung carcinoma

    PubMed Central

    2012-01-01

    Background Snail is a transcriptional factor which is known to influence the epitheliomesenchymal transition (EMT) by regulating adhesion proteins such as E-cadherin and claudins as well as matrix metalloproteases (MMP). Methods To evaluate the functional importance of snail, a transciptional factor involved in EMT in lung tumors, we investigated its expression in a large set of lung carcinomas by immunohistochemistry. Expression of snail and effects of snail knockdown was studied in cell lines. Results Nuclear snail expression was seen in 21% of cases this being strongest in small cell lung carcinomas (SCLC). There was significantly greater snail expression in SCLC compared to squamous cell or adenocarcinoma. Positive snail expression was associated with poor survival in the whole material and separately in squamous cell and adenocarcinomas. In Cox regression analysis, snail expression showed an independent prognostic value in all of these groups. In several cell lines knockdown of snail reduced invasion in both matrigel assay and in the myoma tissue model for invasion. The influence of snail knockdown on claudin expression was cell type specific. Snail knockdown in these cell lines modified the expression of MMP2 and MMP9 but did not influence the activation of these MMPs to any significant degree. Conclusions The results show that snail plays an important role in the invasive characteristics of lung carcinoma influencing the survival of the patients. Snail knockdown might thus be one option for targeted molecular therapy in lung cancer. Snail knockdown influenced the expression of claudins individually in a cell-line dependent manner but did not influence MMP expressions or activations to any significant degree. PMID:23157169

  3. Effects of dietary fat on spontaneous metastasis of Lewis lung carcinoma and changes in plasma cytokine concentrations in mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The present study assessed the effects of dietary fat on spontaneous metastasis of Lewis lung carcinoma in mice. Three-week old male C57BL/6 mice were fed the AIN-93G standard diet or a 45% fat diet (kcal %) for seven weeks before they were subcutaneously injected with 2.5 x 105 viable cells into th...

  4. Mucoepidermoid carcinoma of the conjunctiva with lung metastasis.

    PubMed

    Rishi, Pukhraj; Sharma, Rashi; Subramanian, Krishnakumar; Subramaniam, Nirmala

    2015-05-01

    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. PMID:26139812

  5. The continuing role of epidermal growth factor receptor tyrosine kinase inhibitors in advanced squamous cell carcinoma of the lung

    PubMed Central

    Tan, Wan Ling

    2016-01-01

    Squamous cell carcinoma (SCC) of the lung represents about 20-30% of non-small cell lung cancers (NSCLC) and is associated with a poorer prognosis with limited treatment options. Erlotinib is an approved, standard second-line therapy in this setting, besides docetaxel. The LUX-Lung 8 study has shown superior overall survival (OS), progression-free survival (PFS), as well as disease control rates for treatment with afatinib compared to erlotinib in this head-to-head trial in patients with previously treated advanced SCC of the lung, with manageable side effect profile. This is the first and largest prospective phase III trial comparing two different tyrosine kinase inhibitors in patients with advanced SCC of the lung. Whether the results would be practice-changing remains to be seen, especially with the advent of novel immunotherapeutic agents such as nivolumab, which is recently approved for advanced lung SCC. PMID:26958503

  6. A Case Report of 20 Lung Radiofrequency Ablation Sessions for 50 Lung Metastases from Parathyroid Carcinoma Causing Hyperparathyroidism

    SciTech Connect

    Tochio, Maki Takaki, Haruyuki; Yamakado, Koichiro; Uraki, Junji; Kashima, Masataka; Nakatsuka, Atsuhiro; Takao, Motoshi; Shimamoto, Akira; Tarukawa, Tomohito; Shimpo, Hideto; Takeda, Kan

    2010-06-15

    A 47-year-old man presented with multiple lung metastases from parathyroid carcinoma that caused hyperparathyroidism and refractory hypercalcemia. Lung radiofrequency (RF) ablation was repeated to decrease the serum calcium and parathyroid hormone levels and improve general fatigue. Pulmonary resection was combined for lung hilum metastases. The patient is still alive 4 years after the initial RF session. He has received 20 RF sessions for 50 lung metastases during this period.

  7. Intrameningioma Metastasis: Clinical Manifestation of Occult Primary Lung Carcinoma.

    PubMed

    Nadeem, Muhammad; Assad, Salman; Nasir, Humaira; Mansoor, Salman; Khan, Innayatullah; Manzoor, Hana; Kiani, Immad; Raja, Avais; Sulehria, Touqeer

    2016-01-01

    We report a case of lung carcinoma metastasizing into a meningioma in a 68-year-old female, who presented with progressively worsening right-sided hemiparesis and multiple episodes of adult onset epilepsy. Magnetic resonance imaging revealed an oval-shaped extra-axial hypointense lesion with a central hyperintense nodule in the left frontal region favoring a most probable diagnosis of a meningioma. Left frontoparietal craniotomy and excision of the tumor were carried out and histopathology with hematoxylin and eosin stain revealed a meningioma with metastatic adenocarcinoma and was confirmed by immunohistochemistry. The origin of metastasis was presumed to be from the lungs. A computed tomography (CT) scan of the chest with contrast showed a 3.1 x 2.9 cm mass with spiculated margins in the left lower lobe. Fine needle aspiration cytology (FNAC) proved it to be adenocarcinoma. PMID:27588225

  8. Intrameningioma Metastasis: Clinical Manifestation of Occult Primary Lung Carcinoma

    PubMed Central

    Nadeem, Muhammad; Nasir, Humaira; Mansoor, Salman; Khan, Innayatullah; Manzoor, Hana; Kiani, Immad; Raja, Avais; Sulehria, Touqeer

    2016-01-01

    We report a case of lung carcinoma metastasizing into a meningioma in a 68-year-old female, who presented with progressively worsening right-sided hemiparesis and multiple episodes of adult onset epilepsy. Magnetic resonance imaging revealed an oval-shaped extra-axial hypointense lesion with a central hyperintense nodule in the left frontal region favoring a most probable diagnosis of a meningioma. Left frontoparietal craniotomy and excision of the tumor were carried out and histopathology with hematoxylin and eosin stain revealed a meningioma with metastatic adenocarcinoma and was confirmed by immunohistochemistry. The origin of metastasis was presumed to be from the lungs. A computed tomography (CT) scan of the chest with contrast showed a 3.1 x 2.9 cm mass with spiculated margins in the left lower lobe. Fine needle aspiration cytology (FNAC) proved it to be adenocarcinoma. PMID:27588225

  9. Unresectable Squamous Cell Carcinoma of the Lung: An Outcomes Study

    SciTech Connect

    Newlin, Heather E.; Iyengar, Meera; Morris, Christopher G.; Olivier, Kenneth

    2009-06-01

    Purpose: To report survival and control rates in patients with inoperable squamous cell carcinoma (SCC). Methods and Materials: Two hundred seventy-five patients with inoperable squamous cell carcinoma of the lung (Stages I-IIIB) who received radiotherapy alone or combined with chemotherapy given with curative intent at University of Florida between 1963 and 2006 were retrospectively analyzed. Results: Overall survival (OS) at 5 years for Stages I, II, and III was 10%, 14%, and 7% (p = 0.0034); local-regional control at 5 years was 51%, 38%, and 29% (p = 0.0003); and freedom from metastases at 5 years was 81%, 60%, and 65% (p = 0.0689), respectively. Patients who received doses {>=} 65 Gy had improved cause-specific survival (CSS), OS, and metastasis-free survival at 5 years compared with those who received doses < 65 Gy. Five-year regional control was significantly improved with twice-daily vs. once-daily treatment (37% vs. 14%, p = 0.02). Chemotherapy significantly improved 5-year regional control (36% for patients who received chemotherapy vs. 13% for those who did not; p = 0.01). Conclusions: Dose escalation, accelerated fractionation, and combined modality therapies improve outcomes in SCC of the lung. Our review of the literature highlights the different natural history for SCC vs. other non-small cell lung cancers and emphasizes the importance of tailoring treatment strategies to individual patients. At University of Florida, we have begun treating unresectable Stage III patients with SCC of the lung using 69.6 Gy twice daily with concurrent chemotherapy.

  10. Comprehensive histologic analysis of ALK-rearranged lung carcinomas.

    PubMed

    Yoshida, Akihiko; Tsuta, Koji; Nakamura, Harumi; Kohno, Takashi; Takahashi, Fumiaki; Asamura, Hisao; Sekine, Ikuo; Fukayama, Masashi; Shibata, Tatsuhiro; Furuta, Koh; Tsuda, Hitoshi

    2011-08-01

    A subset (1% to 5%) of non-small-cell lung carcinomas harbors the EML4-ALK fusion gene. Data from previous studies on the histomorphology of ALK-rearranged lung cancer are inconsistent, and the specific histologic parameters that characterize this subset and how accurately such parameters predict underlying ALK abnormality remain uncertain. To answer these questions, we performed a comprehensive histologic analysis of 54 surgically resected, extensively sampled ALK-rearranged lung carcinomas and compared them with 100 consecutive resections of ALK-wild-type lung cancers. All 54 cases showed at least a focal adenocarcinoma component, and 3 and 2 cases had additional squamous and sarcomatoid differentiation, respectively. Solid or acinar growth pattern, cribriform structure, presence of mucous cells (signet-ring cells or goblet cells), abundant extracellular mucus, lack of lepidic growth, and lack of significant nuclear pleomorphism were more common in ALK-positive cancers. Two recognizable constellations of findings, a solid signet-ring cell pattern and a mucinous cribriform pattern, were present at least focally in the majority (78%) of ALK-positive tumors, but were rare (1%) in ALK-negative tumors. Multivariate analysis showed that a combination of these 2 patterns was the most powerful histologic indicator of ALK rearrangement. Characteristic histologies were present both in primary sites and in metastases. Thus, histologic findings may help to identify cases for ALK testing. However, none of the histologic parameters were completely sensitive or specific to ALK rearrangement, and histomorphology should not replace confirmatory molecular or immunohistochemical studies. ALK-positive cancers commonly showed coexpression of thyroid transcription factor-1 and p63, and its significance is currently unclear. PMID:21753699

  11. The First Case of Pulmonary Alveolar Proteinosis With Small Cell Lung Carcinoma.

    PubMed

    Hiraki, Tsubasa; Goto, Yuko; Kitazono, Ikumi; Tasaki, Takashi; Higashi, Michiyo; Hatanaka, Kazuhito; Tanimoto, Akihide

    2016-04-01

    Pulmonary alveolar proteinosis (PAP) is a rare pulmonary disease characterized by alveolar accumulation of surfactant lipids and proteins. It is usually autoimmune and secondary to hematologic malignancy or infection. To date, only 5 case reports of PAP associated with lung cancers, including 2 cases of squamous cell carcinoma and 3 cases of adenocarcinoma, have been published. To the best of our knowledge, no case of PAP with small cell lung carcinoma has been reported thus far. We herein report the first case of PAP associated with small cell lung carcinoma. PMID:26519525

  12. The Association Between Alcohol Consumption and Lung Carcinoma by Histological Subtype.

    PubMed

    Troche, Jose Ramon; Mayne, Susan T; Freedman, Neal D; Shebl, Fatma M; Abnet, Christian C

    2016-01-15

    Alcohol is a carcinogen suspected of increasing lung cancer risk. Therefore, we prospectively evaluated the relationship between alcohol consumption and lung carcinoma in 492,902 persons from the National Institutes of Health-AARP Diet and Health Study. We used Cox models to calculate hazard ratios and 95% confidence intervals, adjusting for tobacco smoking and other potential confounders. Between 1995/1996 and December 31, 2006, there were 10,227 incident cases of lung carcinoma, classified as adenocarcinoma (n = 4,036), squamous cell carcinoma (n = 1,998), small cell carcinoma (n = 1,524), undifferentiated carcinoma (n = 559), and other (n = 2,110). Compared with nondrinking, alcohol consumption was associated with a modest nonlinear reduction in total lung carcinoma risk at lower levels of consumption (for 0.5-<1 drink/day, HR = 0.89, 95% confidence interval: 0.82, 0.96) but a modest increase in risk in the highest category (for ≥7 drinks/day, HR = 1.11, 95% confidence interval: 1.00, 1.24). Regarding histological type, alcohol was associated with a nonlinear reduction in squamous cell carcinoma that became attenuated as consumption increased and a modest increase in adenocarcinoma among heavier drinkers. Cubic spline models confirmed these findings. Our data suggest that the relationship between alcohol consumption and lung carcinoma differs by histological subtype. PMID:26672017

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

    PubMed

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

    2016-06-01

    To compare lung adenocarcinoma (ADC) and lung squamous cell carcinoma (SqCC) and to identify new drivers of lung carcinogenesis, we examined the exome sequences and copy number profiles of 660 lung ADC and 484 lung SqCC tumor-normal pairs. Recurrent alterations in lung SqCCs were more similar to those of other squamous carcinomas than to alterations in lung ADCs. New significantly mutated genes included PPP3CA, DOT1L, and FTSJD1 in lung ADC, RASA1 in lung SqCC, and KLF5, EP300, and CREBBP in both tumor types. New amplification peaks encompassed MIR21 in lung ADC, MIR205 in lung SqCC, and MAPK1 in both. Lung ADCs lacking receptor tyrosine kinase-Ras-Raf pathway alterations had mutations in SOS1, VAV1, RASA1, and ARHGAP35. Regarding neoantigens, 47% of the lung ADC and 53% of the lung SqCC tumors had at least five predicted neoepitopes. Although targeted therapies for lung ADC and SqCC are largely distinct, immunotherapies may aid in treatment for both subtypes. PMID:27158780

  14. Multicolor fluorescence in situ hybridization and comparative genomic hybridization reveal molecular events in lung adenocarcinomas and squamous cell lung carcinomas.

    PubMed

    Shen, Hua; Gao, Wen; Wu, Yu-jie; Qiu, Hai-rong; Shu, Yong-qian

    2009-07-01

    We have used the molecular cytogenetic techniques of multicolor fluorescence in situ hybridization (M-FISH) and comparative genomic hybridization (CGH) to analyze two established lung cancer cell lines (A549, H520), 80 primary lung adenocarcinoma samples and 80 squamous cell lung carcinoma samples in order to identify common chromosomal aberrations. M-FISH revealed numerous complex chromosomal rearrangements. Chromosomes 5, 6, 11, 12, and 17 were most frequently involved in interchromosomal translocations. CGH revealed regions on 1q, 2p, 3q, 5p, 5q, 7p, 8q, 11q, 12q, 14q, 16p, 17p, 19q, 20q, 21q and 22q to be commonly over-represented and regions on 2q, 3p, 4p, 5q, 7q, 8p, 9p, 13q, 14q, and 17p to be under-represented. In lung adenocarcinomas the most common gains were found in 16p13 (50%); while in squamous cell lung carcinomas the common gains were found in 17q21 (45%) and these alterations were observed to be associated with their specific pathological subtype. In conclusion, the present study contributes to the molecular biological characterization in lung adenocarcinomas and squamous cell lung carcinomas and through evaluation of molecular events to the recently emergent focus on novel markers for lung cancer treatment. PMID:18848758

  15. Inferring RBP-Mediated Regulation in Lung Squamous Cell Carcinoma

    PubMed Central

    Lafzi, Atefeh; Kazan, Hilal

    2016-01-01

    RNA-binding proteins (RBPs) play key roles in post-transcriptional regulation of mRNAs. Dysregulations in RBP-mediated mechanisms have been found to be associated with many steps of cancer initiation and progression. Despite this, previous studies of gene expression in cancer have ignored the effect of RBPs. To this end, we developed a lasso regression model that predicts gene expression in cancer by incorporating RBP-mediated regulation as well as the effects of other well-studied factors such as copy-number variation, DNA methylation, TFs and miRNAs. As a case study, we applied our model to Lung squamous cell carcinoma (LUSC) data as we found that there are several RBPs differentially expressed in LUSC. Including RBP-mediated regulatory effects in addition to the other features significantly increased the Spearman rank correlation between predicted and measured expression of held-out genes. Using a feature selection procedure that accounts for the adaptive search employed by lasso regularization, we identified the candidate regulators in LUSC. Remarkably, several of these candidate regulators are RBPs. Furthermore, majority of the candidate regulators have been previously found to be associated with lung cancer. To investigate the mechanisms that are controlled by these regulators, we predicted their target gene sets based on our model. We validated the target gene sets by comparing against experimentally verified targets. Our results suggest that the future studies of gene expression in cancer must consider the effect of RBP-mediated regulation. PMID:27186987

  16. Creatine kinase activity and isoenzymes in lung, colon and liver carcinomas.

    PubMed Central

    Joseph, J.; Cardesa, A.; Carreras, J.

    1997-01-01

    We have compared the levels of creatine kinase (CK) activity and the distribution of CK isoenzymes determined by agarose gel electrophoresis in normal colon, liver and lung tissues, and in colon, liver and lung adenocarcinomas, lung squamous cell carcinomas and lung carcinoids. Colon and lung adenocarcinomas, and squamous cell carcinomas presented lower CK activity than the normal tissues and no differences were found between hepatocarcinoma and normal liver tissue. In contrast, lung carcinoids had higher CK activity than normal lung tissue. Type BB-CK was the predominant isoenzyme in normal lung, colon and liver tissues. Type MM isoenzyme was detected in normal lung and type MB-CK was found in normal colon. In most lung tumours the CK isoenzyme electrophoretic pattern did not change. However, no type BB-CK was detected in some hepatocarcinomas, type MM-CK decreased in lung carcinoids and type MB isoenzyme was not observed in colon adenocarcinomas. It is concluded that in most tumours there is a decrease in the expression of type B- and type M-CK subunits, whereas in lung carcinoid the expression of type B-CK activity increases. Thus, the increase in type BB-CK observed in the serum of patients with lung and colon adenocarcinomas is probably due mainly to enhanced enzyme release as a result of tumour cell necrosis. Images Figure 1 Figure 2 Figure 3 PMID:9303358

  17. Regulation of neutrophil gelatinase-associated lipocalin expression by C/EBPβ in lung carcinoma cells

    PubMed Central

    ZHANG, PI-XIAN; CHANG, JING-XIA; XIE, JIAN-JUN; YUAN, HUA-MIN; DU, ZE-PENG; ZHANG, FA-REN; LÜ, ZHUO; XU, LI-YAN; LI1, EN-MIN

    2012-01-01

    Neutrophil gelatinase-associated lipocalin (NGAL), a member of the lipocalin family, has been found to be overexpressed in a variety of tumors, including lung adenocarcinomas. However, the mechanism by which NGAL expression is regulated in lung carcinoma needs further evaluation. In this study, immunohistochemistry was employed to analyze the expression of NGAL in lung carcinoma tissue samples, including lung squamous carcinomas, adenocarcinomas, adenosquamous carcinomas and bronchial alveolar cell carcinomas. The results showed that NGAL was expressed in 82.61% (19/23) of the samples. RT-PCR and immunofluorescent staining showed that NGAL was localized to the cytoplasm in lung carcinoma cell lines. To explore the transcriptional regulation mechanism of NGAL basal expression in lung carcinoma, a 1515-bp fragment (−1431 to +84) of the NGAL promoter region was cloned and a series of deletion and mutation constructs were generated. These constructs were analyzed using the luciferase reporter assay. The results indicated that the cis-acting elements important for the basal activity of NGAL transcription were likely located between −152 and −141. Further analysis using site-directed mutagenesis and the luciferase reporter assay suggested that the C/EBP binding sites were responsible for the activity of the NGAL promoter. Finally, the binding ability and specificity of the transcription factors were determined by electrophoretic mobility-shift assay (EMSA). The results showed that C/EBPβ was able to bind to the −152 and −141 segments. Taken together, these findings suggest that NGAL is expressed in lung carcinomas and that NGAL expression is mediated by the binding of C/EBPβ to the −152 and −141 segment of the NGAL promoter. PMID:23162623

  18. Curative radiotherapy in non-small cell carcinoma of the lung

    SciTech Connect

    Talton, B.M.; Constable, W.C.; Kersh, C.R. )

    1990-07-01

    Recent reports suggest radiotherapy administered to the 5000-6000 cGy level can result in significant long-term survival in non-small cell carcinoma of the lung. This is particularly true for many cases that are technically operable but for medical or other reasons thoracotomy cannot be performed. Such patients drawn from Southern Appalachia where the principal industry is coal mining are the subject of this report. In this region coal miners pneumoconiosis (black lung) is common as well as other chronic respiratory disorders resulting in poor tolerance for surgery. Three hundred and eleven cases of non-small cell carcinoma were irradiated during the 4 years of 1980 through 1983. This group consisted of 77 patients with clinical Stage T1, T2, T3 all N0, M0 tumors, the majority of which were technically operable but upon whom no thoracotomy was performed because of medical reasons or patient refusal. All are available for 5-year study. Each of these patients was uniformly irradiated to 6000 cGy target dose in 30 fractions over 6 weeks using standard techniques.Comparison with reported surgical series treated for cure show little difference in survival up to 2 years. Thereafter, the survival curves diverge with radiotherapy patients dying at a somewhat higher rate although by 4 years both survival curves slope similarly. A possible explanation for this difference is the advantage thoracotomy offers in early case selection allowing exclusion of advance cases from surgical reports whereas radiotherapy must include patients with occult local metastasis not identifiable on clinical grounds. This experience, among other reports include evidence that radiotherapy can result in long-term survival or cure with minimal morbidity in lung cancer patients in whom surgery carries excessive risk.

  19. Metastatic large cell neuroendocrine carcinoma of the lung arising from the uterus: A pitfall in lung cancer diagnosis.

    PubMed

    Ono, Kyoko; Yokota, Naho Ruiz; Yoshioka, Emi; Noguchi, Akira; Washimi, Kota; Kawachi, Kae; Miyagi, Yohei; Kato, Hisamori; Yokose, Tomoyuki

    2016-07-01

    A 41-year-old female smoker presented with a vaginal mass. Gynecological examination showed a mass filling the uterine corpus, cervix, and vagina. A total abdominal hysterectomy was performed. Macroscopic findings included a large fragile mass involving the uterine cavity, cervix, and vagina. Histology revealed atypical ducts admixed with solid components consisting of large atypical cells. The initial pathological diagnosis was grade 3 endometrioid adenocarcinoma. The patient was designated as stage II according to the 2008 International Federation of Gynecology and Obstetrics (FIGO) staging. Two years later, two nodules were found in the upper lobe of the left lung, and the patient underwent an upper lobectomy. The masses, which exhibited solid and organoid growth patterns of large atypical cells, had histological characteristics of large cell neuroendocrine carcinoma (LCNEC) of the lung. However, the tumor was immunohistochemically positive for neuroendocrine markers, such as synaptophysin in addition to estrogen receptor and progesterone receptor, and the tumor was negative for thyroid transcription factor-1. These immunohistochemical results were almost identical to those of the solid portions of the uterine carcinoma. The final diagnosis was LCNEC combined with endometrioid adenocarcinoma of the uterine corpus and lung metastasis of the LCNEC component of the endometrial carcinoma. LCNEC often arises in the lung, but it rarely arises in other organs. Some patients with metastatic components exhibited only a LCNEC pattern although the primary tumor was a mixed carcinoma consisting of LCNEC and other histology, like the present case. LCNEC is often poorly differentiated, especially in extrapulmonary primary organ LCNEC. Therefore, pathologists should consider metastatic carcinoma when they encounter lung LCNEC in a patient with a preceding extrapulmonary carcinoma composed of a poorly differentiated component or LCNEC component, and they should clarify tumor

  20. Jejunal intussusception caused by metastasis of a giant cell carcinoma of the lung

    PubMed Central

    Fujii, Yuki; Homma, Shigenori; Yoshida, Tadashi; Taketomi, Akinobu

    2016-01-01

    A 55-year-old woman was admitted to our hospital reporting of nausea, vomiting and anorexia. One month before admission, she had been diagnosed with lung cancer with intestinal metastasis. A CT scan confirmed intussusception due to intestinal metastasis and she underwent emergency laparoscopic surgery followed by resection of the primary lung cancer. Histopathological findings of the intestinal specimen suggested the metastasis was from a giant cell carcinoma of the lung, which had extensive necrosis. She was still alive without recurrence 11 months after the first surgery. Giant cell carcinoma of the lung is a rare type of non-small cell carcinoma and intestinal metastasis is one of the unique features. This type of tumour has such aggressive characteristics that oncological prognosis is reported to be extremely poor. In our case, however, complete surgical resection of both primary and metastatic tumours might result in a better outcome than has been reported. PMID:27485876

  1. Jejunal intussusception caused by metastasis of a giant cell carcinoma of the lung.

    PubMed

    Fujii, Yuki; Homma, Shigenori; Yoshida, Tadashi; Taketomi, Akinobu

    2016-01-01

    A 55-year-old woman was admitted to our hospital reporting of nausea, vomiting and anorexia. One month before admission, she had been diagnosed with lung cancer with intestinal metastasis. A CT scan confirmed intussusception due to intestinal metastasis and she underwent emergency laparoscopic surgery followed by resection of the primary lung cancer. Histopathological findings of the intestinal specimen suggested the metastasis was from a giant cell carcinoma of the lung, which had extensive necrosis. She was still alive without recurrence 11 months after the first surgery. Giant cell carcinoma of the lung is a rare type of non-small cell carcinoma and intestinal metastasis is one of the unique features. This type of tumour has such aggressive characteristics that oncological prognosis is reported to be extremely poor. In our case, however, complete surgical resection of both primary and metastatic tumours might result in a better outcome than has been reported. PMID:27485876

  2. Extensive tumor thrombus in a case of carcinoma lung detected by F18-FDG-PET/CT.

    PubMed

    Mudalsha, Ravina; Jacob, Mj; Pandit, Ag; Jora, Charu

    2011-04-01

    Tumor thrombus is a rare complication of solid cancers, mainly seen in cases of renal cell carcinoma, wilm's tumor, testicular carcinoma, adrenal cortical carcinoma and hepatocellular carcinoma.[1] Tumor thrombus in inferior vena cava is a rare complication of primary carcinoma lung. It should be identified so as to rule out venous thromboembolism and avoiding unnecessary anticoagulant therapy. We describe a case where F18-Fluorodeoxyglucose (FDG) positron emission tomography - computed tomography (PET/CT) helped to identify extensive tumor thrombus. PMID:22174524

  3. Extensive tumor thrombus in a case of carcinoma lung detected by F18-FDG-PET/CT

    PubMed Central

    Mudalsha, Ravina; Jacob, MJ; Pandit, AG; Jora, Charu

    2011-01-01

    Tumor thrombus is a rare complication of solid cancers, mainly seen in cases of renal cell carcinoma, wilm's tumor, testicular carcinoma, adrenal cortical carcinoma and hepatocellular carcinoma.[1] Tumor thrombus in inferior vena cava is a rare complication of primary carcinoma lung. It should be identified so as to rule out venous thromboembolism and avoiding unnecessary anticoagulant therapy. We describe a case where F18-Fluorodeoxyglucose (FDG) positron emission tomography - computed tomography (PET/CT) helped to identify extensive tumor thrombus. PMID:22174524

  4. Primary salivary duct carcinoma of the lung, mucin-rich variant.

    PubMed

    Fishbein, Gregory A; Grimes, Brandon S; Xian, Rena R; Lee, Jay M; Barjaktarevic, Igor; Xu, Haodong

    2016-01-01

    Primary salivary gland-type lung cancer is a heterogeneous group of neoplasms arising from the seromucinous glands of the respiratory tract. Histopathologically, they are identical to salivary gland neoplasms of the head and neck. While mucoepidermoid carcinoma and adenoid cystic carcinoma are overwhelmingly the most common subtypes found in the lung, reports of uncommon subtypes can be found in the literature. We report a case of a 73-year-old woman with primary lung salivary duct carcinoma, mucin-rich variant--an exceedingly rare subtype of an already rare malignant salivary-type neoplasm. One case of primary lung salivary duct carcinoma has been reported in the literature; however, the mucin-rich variant has never been described in the lung. Furthermore, the tumor in our case bears a rare BRAF G464V mutation. To our knowledge, this is the first reported case of a BRAF G464V mutation detected in a salivary duct carcinoma or any other salivary-type neoplasm. PMID:26527521

  5. Chemoprevention of lung squamous cell carcinoma in mice by a mixture of Chinese herbs.

    PubMed

    Wang, Yian; Zhang, Zhongqiu; Garbow, Joel R; Rowland, Doug J; Lubet, Ronald A; Sit, Daniel; Law, Francis; You, Ming

    2009-07-01

    Antitumor B (ATB) is a Chinese herbal mixture of six plants. Previous studies have shown significant chemopreventive efficacy of ATB against human esophageal and lung cancers. We have recently developed a new mouse model for lung squamous cell carcinomas (SCC). In this study, lung SCC mouse model was characterized using small-animal imaging techniques (magnetic resonance imaging and computed tomography). ATB decreased lung SCC significantly (3.1-fold; P < 0.05) and increased lung hyperplastic lesions by 2.4-fold (P < 0.05). This observation suggests that ATB can block hyperplasia from progression to SCC. ATB tissue distribution was determined using matrine as a marker chemical. We found that ATB is rapidly absorbed and then distributes to various tissues including the lung. These results indicate that ATB is a potent chemopreventive agent against the development of mouse lung SCCs. PMID:19584077

  6. The diagnostic utility of the triple markers Napsin A, TTF-1, and PAX8 in differentiating between primary and metastatic lung carcinomas.

    PubMed

    El-Maqsoud, Nehad M R Abd; Tawfiek, Ehab Rifat; Abdelmeged, Ayman; Rahman, Mohamed Fathy Abdel; Moustafa, Alaa A E

    2016-03-01

    Napsin A and thyroid transcription factor-1 (TTF-1) are useful biomarkers for differentiating lung adenocarcinoma from squamous cell carcinoma and also for differentiating primary lung adenocarcinoma from metastatic lung carcinoma. Pair-boxed 8 (PAX8) can help in distinguishing primary lung carcinoma from metastatic carcinomas and help to determine the primary sites of metastatic carcinomas. Immunohistochemistry for Napsin A, TTF-1, and PAX8 were performed on 193 cases of carcinoma: 50 primary lung carcinoma and 143 carcinomas from other sites. Napsin A and TTF-1 were positive in 54, 52 % of lung carcinomas cases, respectively. While in adenocarcinoma cases, their expressions were 86.7 and 83.3 %, respectively. PAX8 was negative in all lung carcinomas. TTF-1 and PAX8 were positive in 93.3 and 96.7 % of thyroid carcinoma cases and in 87.5 and 93.8 % of papillary carcinoma respectively, and both were positive in 100 % of follicular carcinoma. Napsin A was negative in all thyroid carcinomas. Napsin A and PAX8 were positive in 50 and 93.3 % of renal carcinoma cases and in 81.8 and 100 % of papillary carcinoma, 38.5 and 92.3 % of clear cell carcinoma, and 16.7 and 83.3 % of chromophobe carcinoma respectively. TTF-1 was negative in all renal carcinomas. PAX8 was positive in 80 % of ovarian carcinoma cases; 100 and 60 % of serous mucinous carcinomas, respectively. It was also positive in 100 % of endometrial carcinoma. Napsin A and TTF-1 were negative in both ovarian and endometrial carcinomas. Our data demonstrated that combined use of Napsin A, TTF-1, and PAX8 may help in differentiating between primary lung adenocarcinoma and metastatic lung carcinomas. PMID:26427663

  7. Pneumonia carcinomatosa from small cell undifferentiated carcinoma of the lung presenting as reverse radiation pneumonitis

    SciTech Connect

    Adelstein, D.J.; Padhya, T.; Tomashefski, J.F. Jr.; Park, C.

    1988-01-01

    We describe a patient with recurrent small cell undifferentiated lung carcinoma after chemotherapy and mediastinal radiation therapy who presented with peripheral pulmonary infiltrates on chest radiograph. At autopsy the patient was found to have carcinomatous pneumonia confined to the radiographically abnormal lung. The descriptive term reverse radiation pneumonitis is applied in view of the striking nonsegmental distribution of these pulmonary infiltrates, which occurred only outside the irradiated field. In this patient, radiation therapy successfully controlled disease in the treated lung parenchyma, thus accounting for this unusual radiologic and histologic picture. Pneumonia carcinomatosa, occurring after lung irradiation, can therefore be added to the differential diagnosis of radiographic peripheral pulmonary infiltrates.

  8. Dietary supplementation with methylseleninic acid, but not selenomethionine, reduces spontaneous metastasis of Lewis lung carcinoma in mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Dietary supplementation with methylseleninic acid reduces spontaneous metastasis of Lewis lung carcinoma in mice Lin Yan*, Lana C. DeMars The present study investigated the effects of dietary supplementation with methylseleninic acid (MSeA) on spontaneous metastasis of Lewis lung carcinoma (LLC) in...

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

    PubMed

    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. PMID:27114369

  10. Spontaneous regression in advanced squamous cell lung carcinoma

    PubMed Central

    Park, Yeon Hee; Park, Bo Mi; Park, Se Yeon; Choi, Jae Woo; Kim, Sun Young; Kim, Ju Ock; Jung, Sung Soo; Park, Hee Sun; Moon, Jae Young

    2016-01-01

    Spontaneous regression of malignant tumors is rare especially of lung tumor and biological mechanism of such remission has not been addressed. We report the case of a 79-year-old Korean patient with non-small cell lung cancer, squamous cell cancer with a right hilar tumor and multiple lymph nodes, lung to lung metastasis that spontaneously regressed without any therapies. He has sustained partial remission state for one year and eight months after the first histological diagnosis. PMID:27076978

  11. [Treatment of non-small cell lung carcinoma in early stages].

    PubMed

    Meneses, José Carlos; Avila Martínez, Régulo J; Ponce, Santiago; Zuluaga, Mauricio; Bartolomé, Adela; Gámez, Pablo

    2013-12-01

    Treatment of lung carcinoma is multidisciplinary. There are different therapeutic strategies available, although surgery shows the best results in those patients with lung carcinoma in early stages. Other options such as stereotactic radiation therapy are relegated to patients with small tumors and poor cardiopulmonary reserve or to those who reject surgery. Adjuvant chemotherapy is not justified in patients with stage i of the disease and so double adjuvant chemotherapy should be considered. This adjuvant chemotherapy should be based on cisplatin after surgery in those patients with stages ii and IIIA. PMID:23829961

  12. Normal adrenal glands in small cell lung carcinoma: CT-guided biopsy

    SciTech Connect

    Pagani, J.J.

    1983-05-01

    Twenty-four small cell lung carcinoma patients with morphologically normal adrenal glands by computed tomographic (CT) criteria underwent percutaneous thin-needle biopsy of their adrenal glands. Of 43 glands biopsied, 29 had adequate cellular material for interpretation. Five (17%) of the 29 glands were positive for metastases; the rest had negative biopsies. This series indicates an approximate 17% false-negative diagnosis rate by CT when staging the adrenal glands in patients with small cell lung carcinoma. It also demonstrates the utility of percutaneous needle biopsy as an investigational tool to further evaluate normal-sized adrenal glands in the oncologic patient.

  13. Digital Acrometastasis as Initial Presentation in Carcinoma of Lung A Case Report and Review of Literature

    PubMed Central

    Sahoo, Tapan Kumar; Das, Saroj Kumar; Majumdar, Saroj Kumar Das; Senapati, Surendra Nath

    2016-01-01

    Bony metastases develop in 30% of all the cancers, but out of which only 1% to 3% occurs in the hand. Lung is the most common site for acrometastasis, followed by breast and renal cell cancer. Metastases to the digits are with non-specific presentation. We reported a case of 79-year-old male patient with initial presentation of swelling over left index finger, which was found to be squamous cell carcinoma of finger on histopathological examination. He was subsequently diagnosed as a case of squamous cell carcinoma of lung with acrometastasis. PMID:27504389

  14. Digital Acrometastasis as Initial Presentation in Carcinoma of Lung A Case Report and Review of Literature.

    PubMed

    Sahoo, Tapan Kumar; Das, Saroj Kumar; Majumdar, Saroj Kumar Das; Senapati, Surendra Nath; Parida, Dillip Kumar

    2016-06-01

    Bony metastases develop in 30% of all the cancers, but out of which only 1% to 3% occurs in the hand. Lung is the most common site for acrometastasis, followed by breast and renal cell cancer. Metastases to the digits are with non-specific presentation. We reported a case of 79-year-old male patient with initial presentation of swelling over left index finger, which was found to be squamous cell carcinoma of finger on histopathological examination. He was subsequently diagnosed as a case of squamous cell carcinoma of lung with acrometastasis. PMID:27504389

  15. Lung carcinoma: survey of 2286 cases with emphasis on small cell type.

    PubMed Central

    Hardy, J D; Ewing, H P; Neely, W A; Stauss, H K; Vance, R B

    1981-01-01

    Lung carcinoma is the commonest major malignancy in men in the United States and its incidence is increasing rapidly in women. It is estimated that there will have been 117,000 new cases and 101,300 deaths in 1980. The 2286 patients with lung carcinoma admitted to the Hospital of the University of Mississippi from 1955 to 1980 were reviewed by decades of chronology and of life, with respect to age, cell type, sex and racial incidence. The greatest age incidence was in the sixth and seventh decades; cell types overall were epidermoid (45% of the patients), adenocarcinoma (12% of the patients), small (oat) cell (21% of the patients), and others (22% of the patients). There was a steady increase in the incidence of disease in females, adjusted for total hospital admissions, and a less certain increase among black patients. Twenty-eight per cent of 250 patients with small cell carcinoma so studied exhibited some feature of the paraneoplastic or paraendocrine syndromes. In 41 patients with small cell carcinoma treated with multiple drug chemotherapy, there was an overall response rate of 50% and an additional "stable disease" rate of 28%. Mean survival period in this group was 52 weeks, compared with 12 weeks in patients whose diseases went untreated. Clearly, definite progress is being made, not only in our knowledge of the biology of lung carcinoma, in general, but in the treatment of small cell carcinoma in particular. Images Fig. 4. PMID:6263195

  16. Nivolumab-induced organizing pneumonitis in a patient with lung sarcomatoid carcinoma.

    PubMed

    Gounant, V; Brosseau, S; Naltet, C; Opsomer, M-A; Antoine, M; Danel, C; Khalil, A; Cadranel, J; Zalcman, G

    2016-09-01

    Immune checkpoint inhibitors are known to induce 'immune pneumonitis' in 3-6% of patients treated for lung cancer. However, their dramatic efficacy in as much as 20% of patients led to recent registrations in squamous, and then non-squamous lung carcinoma, in second line setting after failure of first-line chemotherapy, while large phase 3 trials are on-going, to assess first-line immunotherapy, either alone or in combination with chemotherapy. Pulmonary Sarcomatoid carcinomas consist of a rare subset of highly aggressive and poorly differentiated non-small-cell lung carcinomas (NSCLC), with poor prognosis and chemo-resistance. Although exhibiting high expression of programmed death ligand-1 (PD-L1), their sensitivity to inhibitors of PD-1/PD-L1 axis is still unknown. Here we report a case of lung sarcomatoid carcinoma with Nivolumab dramatic and long-lasting efficacy, but occurrence of a very specific pattern of lung toxicity, the so-called 'organizing bronchiolitis syndrome'. As more and more NSCLC patients are promised to receive PD-1 inhibitors as part of their treatment, we feel that specific features of such Nivolumab-induced organizing pneumonitis should be known. Although corticosteroid sensitivity is high, recurrence is frequent because of premature steroid tapering, as for all other causes of organizing pneumonias, and probably because of the Nivolumab long tissue half-life. PMID:27565934

  17. Non-small cell lung carcinoma metastasis to the anus.

    PubMed

    Dhandapani, Ramya Gowri; Anosike, Chinedum; Ganguly, Akash

    2016-01-01

    A 70-year-old man presenting with a lung mass was investigated and treated with pneumonectomy for adenocarcinoma of the lung. He re-presented 3 months later with a large perianal abscess and mass. Subsequent investigations and biopsies showed disseminated metastases from the lung primary. Immunohistochemical staining confirmed the nature of the anal metastasis from the lung adenocarcinoma. Lung cancer is notorious for metastases, hence it is important to be aware of the uncommon modes of spread, which will help obtain early diagnosis and optimise treatment. PMID:27130556

  18. Thermal ablation of stage I non-small cell lung carcinoma.

    PubMed

    Ridge, Carol A; Solomon, Stephen B; Thornton, Raymond H

    2014-06-01

    Ablation options for the treatment of localized non-small cell lung carcinoma (NSCLC) include radiofrequency ablation, microwave ablation, and cryotherapy. Irreversible electroporation is a novel ablation method with the potential of application to lung tumors in risky locations. This review article describes the established and novel ablation techniques used in the treatment of localized NSCLC, including mechanism of action, indications, potential complications, clinical outcomes, postablation surveillance, and use in combination with other therapies. PMID:25053863

  19. Erlotinib in Treating Patients With Advanced Non-Small Cell Lung Cancer, Ovarian Cancer, or Squamous Cell Carcinoma of the Head and Neck

    ClinicalTrials.gov

    2013-01-08

    Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage IIIA Non-small Cell Lung Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IV Non-small Cell Lung Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx

  20. Personalized therapy on the horizon for squamous cell carcinoma of the lung.

    PubMed

    Kim, Han Sang; Mitsudomi, Tetsuya; Soo, Ross A; Cho, Byoung Chul

    2013-06-01

    Squamous cell carcinoma (SQCC) of the lung is the second-largest subtype of non-small cell lung cancer (NSCLC), causing an estimated 400,000 deaths per year worldwide. Recent developments in cancer genome sequencing technology expanded our knowledge of driver mutations, which were identified as novel candidates for targeted therapy in various cancers. Successful targeted treatments for lung adenocarcinoma, NSCLC's primary subtype, with EGFR mutation or ALK fusion are clinically available, and a clinical trial of personalized targeted therapy in patients with lung adenocarcinoma is underway by the Lung Cancer Mutation Consortium. Although there are targeted treatments for lung adenocarcinoma, no personalized therapies currently exist for SQCC. Recently, comprehensive genomic characterization of lung SQCC using massively parallel sequencing has enabled us to identify several potential driver mutations/signaling pathways. These are FGFR1 amplifications, PI3KCA mutations, PTEN mutations/deletions, PDGFRA amplifications/mutations, and DDR2 mutations. The march toward personalized therapy may have taken a step forward with the discovery of these potential biomarkers for the treatment of SQCC of the lung. This article reviewed the current knowledge of genomic landscape of lung SQCC and summarized ongoing clinical trials of targeted agents for lung SQCC. Also, we will suggest several other actionable mutations with matching drugs that should be investigated in future clinical trials for the personalized treatment of lung SQCC. PMID:23489560

  1. Iodine-131 uptake in inflammatory lung disease: a potential pitfall in treatment of thyroid carcinoma

    SciTech Connect

    Hoeschl, R.C.; Choy, D.H.; Gandevia, B.

    1988-05-01

    A mixed differentiated thyroid carcinoma was found in a small asymptomatic nodule in a 44-yr-old woman with recurrent chest infections and bronchiectasis. After total thyroidectomy and 162 mCi (6 GBq) radioiodine ablation there was uptake in the thyroid remnant and in both lungs, interpreted as lung metastases. In 2 years she received further three 162 mCi (6 GBq) doses of /sup 131/I, as scans showed very similar lung activity. Another scan, during thyroxin suppression, showed again activity in the lungs. A 47-yr-old male patient with similar respiratory disease and no history of thyroid disorder volunteered to undergo radioiodine scan while on triiodothyronine suppression. His scan, too, showed concentration in the lungs. The female patient died 7 years after the diagnosis of lung thyroid metastases was made. No metastasis was found at autopsy. Radioiodine lung uptake may occur in patients with chronic inflammatory lung disease, presenting a potential diagnostic pitfall in patients with differentiated thyroid carcinoma.

  2. Lentivirus-mediated silencing of SCIN inhibits proliferation of human lung carcinoma cells.

    PubMed

    Liu, Hongxu; Shi, Daiwang; Liu, Tieqin; Yu, Zhanwu; Zhou, Chuanjiang

    2015-01-01

    SCIN (scinderin) is a calcium-dependent actin severing and capping protein. Homologue in zebrafish has been found to be related with cell death. In the present study, we found that SCIN is highly expressed in human lung cancer specimens. However, the role of SCIN in lung cancer has not yet been determined. To investigate the function of SCIN in lung carcinoma cells, we took advantage of lentivirus-mediated RNA interference (RNAi) to knockdown SCIN expression in two lung carcinoma cell lines A549 and H1299. Silencing of SCIN significantly inhibited the proliferation and colony formation ability of both cell lines in vitro. Moreover, flow cytometry analysis showed that knockdown of SCIN led to G0/G1 phase cell cycle arrest as well as an excess accumulation of cells in the sub-G1 phase. Furthermore, depletion of SCIN resulted in a significant increase in Cyclin B1, p21 and PARP expression, and a little decrease in Cyclin D1 expression. These results suggest that SCIN plays an important role in lung carcinoma cell proliferation, and lentivirus-mediated silencing of SCIN might be a potential therapeutic approach for the treatment of lung cancer. PMID:25303873

  3. Primary Signet Ring Cell Carcinoma of the Lung with Cerebellar Metastasis Showing Full Response to Cisplatin and Docetaxel Therapy

    PubMed Central

    Selcukbiricik, Fatih; Bilici, Ahmet; Kanıtez, Metin; Yildiz, Serdar; Avci, Suna; Tanik, Canan

    2014-01-01

    Introduction. Primary signet ring cell carcinoma (SRCC) of the lung is a very rare disease. We describe a new case of primary SRCC of the lung with cerebellar metastasis, which responded well to the therapeutic approach with cisplatin and docetaxel. Case Report. A 41-year-old female patient (nonsmoker) was consulted to our oncology outpatient clinic after cerebellar metastasectomy. The histopathological diagnosis was SRCC metastasis. The primary tumor was unknown. The PET-CT imaging showed a hypermetabolic mass in the right middle lobe of the lung and hypermetabolic mediastinal lymph node stations. Oesophagogastroduodenoscopy and colonoscopy showed no evidence of gastrointestinal system tumor. The clinical diagnosis of primary SRCC of the lung was made and the administration of six rounds of cisplatin and docetaxel treatment was planned. After the chemotherapy the PET-CT scan to evaluate the therapy response showed full metabolic regression of the primary tumor and the mediastinal lymph nodes. There was no evidence of new metastasis. Conclusion. Primary SRCC of the lung is a very rare disease with poor prognosis. There are not many cases in literature and no standardized chemotherapy protocols. Cisplatin and docetaxel may be a good treatment option. PMID:24716057

  4. Lung metastasis of fatty hepatocellular carcinoma after liver transplant: a case report.

    PubMed

    Tepeoğlu, Merih; Özdemir, B Handan; Ok Atılgan, Alev; Akdur, Aydıncan; Haberal, Mehmet

    2014-03-01

    Hepatocellular carcinoma with prominent fatty change is rare, and to date only a few cases have been reported. In this article, we present a 57-yearold woman who underwent a liver transplant for hepatocellular carcinoma. Ten months after liver transplant, she presented with a persistent cough. Computed tomography of the chest was performed, revealing a solid lung mass that measured 1 × 0.9 cm in the right inferior lobe. Right inferior lobectomy was performed, and the final diagnosis was noted as hepatocellular carcinoma with prominent fatty change. Fatty change was extensive in the tumor; therefore, lipoid pneumonia was the first condition that was considered in the differential diagnosis during examination of the lobectomy material. For the differential diagnosis, the immunohistochemistry panel was studied to show the hepatocellular nature of the tumor. Although metastasis of hepatocellular carcinoma to the lungs is expected, hepatocellular carcinoma with prominent fatty change can cause diagnostic difficulties, such as lipoid pneumonia, especially in small lung biopsies. PMID:24635803

  5. Curcumin reduces trabecular and cortical bone in naive and Lewis lung carcinoma-bearing mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The present study investigated the effects of dietary supplementation with curcumin on bone microstructural changes in female C57BL/6 mice in the presence or absence of Lewis lung carcinoma. Morphometric analysis showed that in tumor-bearing mice curcumin at 2% and 4% dietary levels (w/w) significa...

  6. Dietary supplementation with curcumin enhances metastatic growth of Lewis lung carcinoma in mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The present study investigated the effects of dietary supplementation with curcumin (the principal curcuminoid of the popular Indian spice turmeric) on spontaneous metastasis of Lewis lung carcinoma (LLC) in female C57/BL6 mice. Mice were fed the AIN93G control diet or that diet supplemented with 2...

  7. Epithelial-Myoepithelial Carcinoma of the Salivary Gland Harboring HRAS Codon 61 Mutations With Lung Metastasis.

    PubMed

    Hsieh, Min-Shu; Chen, Jin-Shing; Lee, Yi-Hsuan; Chou, Yueh-Hung

    2016-05-01

    Here, we report a case involving a 43-year-old man diagnosed with Burkitt lymphoma in 2007. At the same time, 2 small lung nodules were incidentally found; however, they presented no indication of growth throughout the follow-up period. However, a 1.5-cm nodule located in the right parotid gland in 2010 gradually increased in size to 2.8 cm by 2012. A parotidectomy revealed an epithelial-myoepithelial carcinoma, characterized by biphasic tubular structures and solid areas presenting myoepithelial overgrowth. Tumor necrosis and regional lymph node invasion were also observed. During clinical follow-up in 2013, a new 1.3-cm nodule was identified in the left lower lobe of the lung, which enlarged to 3 cm by 2014. Wedge resection of the left lung nodules revealed round nodes with well-defined borders. Histologically, these lung tumors predominantly comprised spindle-shaped myoepithelial cells with occasional tubular structures. Numerous cleft-like spaces lined by entrapped TTF-1-immunoreactive pneumocytes were observed inside the nodules. The lung nodules were characterized by a morphology similar to that of the parotid cancer. Epithelial-myoepithelial carcinoma with lung metastasis was confirmed by molecular testing, which revealed identical HRAS codon 61 (Q61K) mutations in the primary parotid tumor as well as in the lung metastases. PMID:26675036

  8. Identification of Prognostic Biomarkers for Progression of Invasive Squamous Cell Carcinoma

    ClinicalTrials.gov

    2016-06-30

    Carcinoma, Squamous Cell; Carcinoma, Squamous; Squamous Cell Carcinoma; Lung Neoplasms; Cancer of Lung; Cancer of the Lung; Lung Cancer; Neoplasms, Lung; Neoplasms, Pulmonary; Pulmonary Cancer; Pulmonary Neoplasms

  9. Pemetrexed and bevacizumab-containing chemotherapy for pleomorphic carcinoma of the lung

    PubMed Central

    TAMURA, TOMOHIRO; OHARA, GEN; KAGOHASHI, KATSUNORI; KAWAGUCHI, MIO; KURISHIMA, KOICHI; SATOH, HIROAKI

    2016-01-01

    Pleomorphic carcinoma of the lung is a rare, highly malignant subtype of lung cancer, with a more aggressive clinical course compared with other types of non-small-cell lung cancer (NSCLC). Pemetrexed and bevacizumab are currently evaluated as two of the most reliable chemotherapeutic drugs for advanced NSCLC. We herein report a case of a 68- and a 46-year-old man with recurrent and chemo-naïve pleomorphic carcinoma of the lung, respectively, who were treated with a combination of carboplatin, pemetrexed and bevacizumab. The overall survival after the initiation of chemotherapy was 30 and 8 months, respectively. These cases exhibited a relatively long-term survival with chemotherapy. In the absence of definitive clinical trials, which are unlikely to be performed due to the rarity of this tumor, our cases demonstrated the potential utility of pemetrexed- and bevacizumab-containing chemotherapy. Our results also suggested that pemetrexed-containing chemotherapy may be key to the treatment of pleomorphic carcinoma of the lung. PMID:27073676

  10. Pleural Small Cell Lung Carcinoma: An Unusual Culprit in Pleural Effusion

    PubMed Central

    Adejorin, Oluwaseyi D.; Sodhi, Amik; Hare, Felicia A.; Headley, Arthur S.; Murillo, Luis C.; Kadaria, Dipen

    2015-01-01

    Patient: Male, 77 Final Diagnosis: Pleural small cell carcinoma Symptoms: Chest pain • shortness of breath Medication: — Clinical Procedure: Thoracocentesis Specialty: Pulmonology Objective: Rare disease Background: Small cell lung carcinoma (SCLC) usually presents as lung or mediastinal lesions. It is very rare for SCLC to present primarily as an isolated pleural effusion with no lung or mediastinal lesions. Case Report: We report the case of a 77-year-old white male with a 60-pack year history of smoking, chronic obstructive pulmonary disease (stage IV), and asbestos exposure who presented with shortness of breath and left lateral chest pain for 7 days. On physical examination, he was very short of breath, with a prolonged expiratory phase on chest auscultation. Laboratory results were normal except for leukocytosis and chest radiograph revealing left-sided pleural effusion. Computerized tomography (CT) scanning of the chest with IV contrast showed left-sided pleural effusion without any lung or mediastinal lesions. Thoracentesis was performed and fluid was sent for analysis. Repeat CT chest/abdomen/pelvis, done immediately following thoracocentesis, did not show any masses or lymphadenopathy. Fluid analysis, including cytology and immunostain pattern, was consistent with small cell carcinoma. Conclusions: Small cell lung cancer presenting as an isolated pleural effusion is extremely rare. It requires close attention to cytology and immunohistochemistry of pleural fluid samples. It also has implications for management and should be managed as limited-stage SCLC. PMID:26714576

  11. Downregulation of MTSS1 expression is an independent prognosticator in squamous cell carcinoma of the lung

    PubMed Central

    Kayser, G; Csanadi, A; Kakanou, S; Prasse, A; Kassem, A; Stickeler, E; Passlick, B; zur Hausen, A

    2015-01-01

    Background: The metastasis suppressor 1 (MTSS1) is a newly discovered protein putatively involved in tumour progression and metastasis. Material and Methods: Immunohistochemical expression of MTSS1 was analysed in 264 non-small-cell lung carcinomas (NSCLCs). Results: The metastasis suppressor 1 was significantly overexpressed in NSCLC compared with normal lung (P=0.01). Within NSCLC, MTSS1 expression was inversely correlated with pT-stage (P=0.019) and histological grading (P<0.001). NSCLC with MTSS1 downregulation (<20%) showed a significantly worse outcome (P=0.007). This proved to be an independent prognostic factor in squamous cell carcinomas (SCCs; P=0.041), especially in early cancer stages (P=0.006). Conclusion: The metastasis suppressor 1 downregulation could thus serve as a stratifying marker for adjuvant therapy in early-stage SCC of the lung. PMID:25625275

  12. Paraneoplastic Limbic Encephalitis in a Male with Squamous Cell Carcinoma of the Lung

    PubMed Central

    Sauri, Tamara; Izquierdo, Àngel; Ramió-Torrentà, LLuis; Sanchez-Montañez, Àngel; Bosch-Barrera, Joaquim

    2015-01-01

    Background Paraneoplastic limbic encephalitis (PLE) is a rare syndrome characterized by memory impairment, symptoms of hypothalamic dysfunction, and seizures. It commonly precedes the diagnosis of cancer. Small-cell lung cancer is the neoplasm that is most frequently reported as the etiology underlying PLE. Case Report This report describes a male patient who presented with neurologic symptoms consistent with anterograde amnesia, apathy, and disorientation. MRI revealed diffuse hyperintensities located predominantly in the medial bitemporal lobes, basal ganglia, frontal lobes, and leptomeninges on fluid attenuated inversion recovery images, suggesting PLE. Study of the primary tumor revealed squamous cell carcinoma of the lung. The patient was treated with neoadjuvant chemotherapy followed by surgery and adjuvant chemoradiotherapy, which resulted in his neurologic symptoms gradually improving. Conclusions PLE might be a rare debut of squamous cell carcinoma of the lung. Treatment of the primary tumor may improve the neurologic symptoms. PMID:25628742

  13. Lung squamous cell carcinoma metastasizing to the nasopharynx following bronchoscopy intervention therapies: a case report

    PubMed Central

    2014-01-01

    Metastatic carcinoma to the nasopharynx is extremely rare, and few cases have been reported in the literature. In the present report, we describe the case of a patient with a mass in the nasopharynx found by bronchoscopy. Our patient was a 61-year-old man receiving multiple bronchoscopy intervention therapies for advanced lung squamous cell carcinoma (SCC), which was histopathologically confirmed. The SCC metastasized to the nasopharynx following the bronchoscopy intervention therapies. The lesion was considered metastatic from lung cancer on the basis of clinical and histological clues. The exact mechanism of lung cancer metastasis to the nasopharynx in this case remains unclear because either implantation or hematogenous and lymphatic spread is possible. A thorough head and neck examination should be undertaken during bronchoscopic evaluation, especially in patients receiving bronchoscopy intervention therapies. The early detection of a silent nasopharyngeal metastasis is important to choosing from among the multiple treatment options available. PMID:24673971

  14. Radiation-induced lung fibrosis after treatment of small cell carcinoma of the lung with very high-dose cyclophosphamide

    SciTech Connect

    Trask, C.W.; Joannides, T.; Harper, P.G.; Tobias, J.S.; Spiro, S.G.; Geddes, D.M.; Souhami, R.L.; Beverly, P.C.

    1985-01-01

    Twenty-five previously untreated patients with small cell carcinoma of the lung were treated with cyclophosphamide 160 to 200 mg/kg (with autologous bone marrow support) followed by radiotherapy (4000 cGy) to the primary site and mediastinum. No other treatment was given until relapse occurred. Nineteen patients were assessable at least 4 months after radiotherapy; of these, 15 (79%) developed radiologic evidence of fibrosis, which was symptomatic in 14 (74%). The time of onset of fibrosis was related to the volume of lung irradiated. A retrospective analysis was made of 20 consecutive patients treated with multiple-drug chemotherapy and an identical radiotherapy regimen as part of a randomized trial. Radiologic and symptomatic fibrosis was one half as frequent (35%) as in the high-dose cyclophosphamide group. Very high-dose cyclophosphamide appears to sensitize the lung to radiotherapy and promotes the production of fibrosis.

  15. “Person in the barrel” syndrome: Unusual heralding presentation of squamous cell carcinoma of the lung

    PubMed Central

    Verma, Rajesh; Lalla, Rakesh; Patil, Tushar B; Babu, Suresh

    2016-01-01

    Paraneoplastic neurological syndromes (PNS) are rare and relatively unusual in day to day clinical practice. Occasionally, PNS may be the heralding manifestation of the malignancy. Paraneoplastic syndromes are most commonly associated with small cell lung carcinoma and are rarely seen with non small cell lung carcinoma. In this case, we report a non-smoker, middle aged lady, who presented with “person in the barrel” syndrome due to myelo radiculoplexopathy as the first clinical manifestation of squamous cell carcinoma of the lung. PMID:27011654

  16. EMX2 Is a Predictive Marker for Adjuvant Chemotherapy in Lung Squamous Cell Carcinomas

    PubMed Central

    Zhang, Yi; Tolani, Bhairavi; Mo, Minli; Zhang, Hua; Zheng, Qingfeng; Yang, Yue; Cheng, Runfen; Jin, Joy Q.; Luh, Thomas W.; Yang, Cathryn; Tseng, Hsin-Hui K.; Giroux-Leprieur, Etienne; Woodard, Gavitt A.; Hao, Xishan; Wang, Changli; Jablons, David M.; He, Biao

    2015-01-01

    Background Squamous cell carcinomas (SCC) account for approximately 30% of non-small cell lung cancer (NSCLC). Current staging methods do not adequately predict outcome for this disease. EMX2 is a homeo-domain containing transcription factor known to regulate a key developmental pathway. This study assessed the significance of EMX2 as a prognostic and predictive marker for resectable lung SCC. Methods Two independent cohorts of patients with lung SCC undergoing surgical resection were studied. EMX2 protein expression was examined by immunohistochemistry, Western blot, or immunofluorescence. EMX2 expression levels in tissue specimens were scored and correlated with patient outcomes. Chemo-sensitivity of lung SCC cell lines stably transfected with EMX2 shRNAs to cisplatin, carboplatin, and docetaxel was examined in vitro. Results EMX2 expression was down-regulated in lung SCC tissue samples compared to their matched adjacent normal tissues. Positive EMX2 expression was significantly associated with improved overall survival in stage I lung SCC patients, and in stage II/IIIA lung SCC patients receiving adjuvant chemotherapy. EMX2 expression was also associated with expression of EMT markers in both lung SCC cell lines and tissue samples. Knock-down of EMX2 expression in lung SCC cells promoted chemo-resistance and cell migration. Conclusions EMX2 expression is down-regulated in lung SCC and its down-regulation is associated with chemo-resistance in lung SCC cells, possibly through regulation of Epithelial-to-Mesenchymal Transition (EMT). EMX2 may serve as a novel prognostic marker for stage I lung SCC patients and a prediction marker for stage II/IIIA lung SCC patients receiving adjuvant chemotherapy. PMID:26132438

  17. SOX2 suppresses CDKN1A to sustain growth of lung squamous cell carcinoma

    PubMed Central

    Fukazawa, Takuya; Guo, Minzhe; Ishida, Naomasa; Yamatsuji, Tomoki; Takaoka, Munenori; Yokota, Etsuko; Haisa, Minoru; Miyake, Noriko; Ikeda, Tomoko; Okui, Tatsuo; Takigawa, Nagio; Maeda, Yutaka; Naomoto, Yoshio

    2016-01-01

    Since the SOX2 amplification was identified in lung squamous cell carcinoma (lung SCC), SOX2 transcriptional downstream targets have been actively investigated; however, such targets are often cell line specific. Here, in order to identify highly consensus SOX2 downstream genes in lung SCC cells, we used RNA-seq data from 178 lung SCC specimens (containing tumor and tumor-associated cells) and analyzed the correlation between SOX2 and previously-reported SOX2-controlled genes in lung SCC. In addition, we used another RNA-seq dataset from 105 non-small cell lung cancer cell lines (NSCLC; including 4 lung SCC cell lines) and again analyzed the correlation between SOX2 and the reported SOX2-controlled genes in the NSCLC cell lines (no tumor-associated cells). We combined the two analyses and identified genes commonly correlated with SOX2 in both datasets. Among the 99 genes reported as SOX2 downstream and/or correlated genes, we found 4 negatively-correlated (e.g., CDKN1A) and 11 positively-correlated genes with SOX2. We used biological studies to demonstrate that CDKN1A was suppressed by SOX2 in lung SCC cells. G1 cell cycle arrest induced by SOX2 siRNA was rescued by CDKN1A siRNA. These results indicate that the tumorigenic effect of SOX2 in lung SCC cells is mediated in part by suppression of CDKN1A. PMID:26846300

  18. Recurrence and survival following resection of bronchioloalveolar carcinoma of the lung--The Lung Cancer Study Group experience.

    PubMed Central

    Grover, F L; Piantadosi, S

    1989-01-01

    Bronchioloalveolar carcinoma (BAC) of the lung is a controversial form of adenocarcinoma with varying presentations. The 1977 to 1988 Lung Study Group experience with this tumor was reviewed to more precisely define the incidence of recurrence and survival of surgically resected and staged patients, to determine the incidence of BAC in the adenocarcinoma population, and to evaluate the impact of age, sex, smoking, and chronic lung-disease history on the incidence of BAC. Of 1635 patients reviewed, 235 patients had pure BAC. It was found that resectable BAC presents at an earlier disease stage than does adenocarcinoma; BAC occurs more frequently in older patients and in those without smoking history or chronic lung disease than adenocarcinoma; BAC patients have less weight loss, brain recurrences, and recurrences without second primaries than adenocarcinoma; survival and recurrence-free survival are better for BAC than for non-BAC adenocarcinoma and large-cell carcinoma; early BAC survival is better than squamous-cell survival but after 2 years is equivalent; T1-N0 BAC patients have recurrence and survival rates similar to squamous-cell survival rates and better than non-BAC adeno survival rates; T1-N1/T2-N0 and Stage 2 and 3 BAC recurs more frequently than either squamous-cell or non-BAC adenocarcinoma; stage 2 and 3 BAC has a higher mortality rate than does squamous-cell carcinoma or non-BAC adenocarcinoma; BAC is a favorable prognostic factor when adjusted for extent of disease and age; and BAC's better prognosis is a result of presenting at an earlier stage of disease and because it appears to be less aggressive than other adenocarcinomas even after adjustment for extent of disease and other known prognostic factors. It is concluded that early diagnosis and resection are particularly important for patients with BAC. Images Fig. 5. Fig. 6. Figs. 7A and B. Fig. 8. PMID:2543339

  19. Obstructive Jaundice from Metastatic Squamous Cell Carcinoma of the Lung.

    PubMed

    Seth, Abhishek; Palmer, Thomas R; Campbell, Jason

    2016-01-01

    Obstructive jaundice from metastatic lung cancer is extremely rare. Most reported cases have had small cell cancer of lung or adenocarcinoma of lung as primary malignancy metastasizing to the biliary system. We report the case of a patient presenting with symptoms of obstructive jaundice found to have metastatic involvement of hepatobiliary system from squamous cell cancer (SCC) of lung. ERCP (endoscopic retrograde cholangiopancreatography) with biliary stenting is the procedure of choice in such patients. Our case is made unique by the fact that technical difficulties made it difficult for the anesthesiologists to intubate the patient for an ERCP. As a result percutaneous transhepatic cholangiogram (PTC) with internal-external biliary drainage was performed. PMID:27389381

  20. An orally administered DNA vaccine targeting vascular endothelial growth factor receptor-3 inhibits lung carcinoma growth.

    PubMed

    Chen, Yan; Liu, Xin; Jin, Cong Guo; Zhou, Yong Chun; Navab, Roya; Jakobsen, Kristine Raaby; Chen, Xiao Qun; Li, Jia; Li, Ting Ting; Luo, Lu; Wang, Xi Cai

    2016-02-01

    Lung cancer is the leading cause of mortality and 5-year survival rate is very low worldwide. Recent studies show that vascular endothelial growth factor receptor-3 (VEGFR-3) signaling pathway contributes to lung cancer progression. So we hypothesize that an oral DNA vaccine that targets VEGFR-3 carried by attenuated Salmonella enterica serovar typhimurium strain SL3261 has impacts on lung cancer progression. In this study, the oral VEGFR-3-based vaccine-immunized mice showed appreciable inhibition of tumor growth and tumor lymphatic microvessels in lung cancer mice model. Moreover, the oral VEGFR-3-based vaccine-immunized mice showed remarkable increases in both VEGFR-3-specific antibody levels and cytotoxic activity. Furthermore, the oral VEGFR-3-based vaccine-immunized mice showed a significant increase in the levels of T helper type 1 (Th1) cell intracellular cytokine expression (IL-2, IFN-γ, and TNF-α). After inoculation with murine Lewis lung carcinoma (LLC) cells, CD4(+) or CD8(+) T cell numbers obviously declined in control groups whereas high levels were maintained in the oral VEGFR-3-based vaccine group. These results demonstrated that the oral VEGFR-3-based vaccine could induce specific humoral and cellular immune responses and then significantly inhibit lung carcinoma growth via suppressing lymphangiogenesis. PMID:26376999

  1. CD10/NEP in non-small cell lung carcinomas. Relationship to cellular proliferation.

    PubMed Central

    Ganju, R K; Sunday, M; Tsarwhas, D G; Card, A; Shipp, M A

    1994-01-01

    The cell surface metalloproteinase CD10/neutral endopeptidase 24.11 (NEP) hydrolyzes a variety of peptide substrates and reduces cellular responses to specific peptide hormones. Because CD10/NEP modulates peptide-mediated proliferation of small cell carcinomas of the lung (SCLC) and normal fetal bronchial epithelium, we evaluated the enzyme's expression in non-small cell lung carcinomas (NSCLC). Bronchoalveolar and large cell carcinoma cell lines had low levels of CD10/NEP expression whereas squamous, adenosquamous, and adenocarcinoma cell lines had higher and more variable levels of the cell surface enzyme. Regional variations in CD10/NEP immunostaining in primary NSCLC specimens prompted us to correlate CD10/NEP expression with cell growth. In primary carcinomas of the lung, clonal NSCLC cell lines and SV40-transformed fetal airway epithelium, subsets of cells expressed primarily CD10/NEP or the proliferating cell nuclear antigen (PCNA). Cultured airway epithelial cells had the lowest levels of CD10/NEP expression when the highest percentage of cells were actively dividing; in addition, these cells grew more rapidly when cell surface CD10/NEP was inhibited. NSCLC cell lines had receptors for a variety of mitogenic peptides known to be CD10/NEP substrates, underscoring the functional significance of growth-related variability in CD10/NEP expression. Images PMID:7962523

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

    SciTech Connect

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

    2014-01-24

    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.

  3. Hedgehog/Gli promotes epithelial-mesenchymal transition in lung squamous cell carcinomas

    PubMed Central

    2014-01-01

    Background Squamous cell carcinomas (SCC) account for approximately 30% of non-small cell lung cancer. Investigation of the mechanism of invasion and metastasis of lung SCC will be of great help for the development of meaningful targeted therapeutics. This study is intended to understand whether the activation of Hedgehog (Hh) pathway is involved in lung SCC, and whether activated Hh signaling regulates metastasis through epithelial-mesenchymal transition (EMT) in lung SCC. Methods Two cohorts of patients with lung SCC were studied. Protein expression was examined by immunohistochemistry, Western blot, or immunofluorescence. Protein expression levels in tissue specimens were scored and correlations were analyzed. Vismodegib and a Gli inhibitor were used to inhibit Shh/Gli activity, and recombinant Shh proteins were used to stimulate the Hh pathway in lung SCC cell lines. Cell migration assay was performed in vitro. Results Shh/Gli pathway components were aberrantly expressed in lung SCC tissue samples. Gli1 expression was reversely associated with the expression of EMT markers E-Cadherin and β-Catenin in lung SCC specimens. Inhibition of the Shh/Gli pathway suppressed migration and up-regulated E-Cadherin expression in lung SCC cells. Stimulation of the pathway increased migration and down-regulated E-Cadherin expression in lung SCC cells. Conclusions Our results suggested that the Shh/Gli pathway may be critical for lung SCC recurrence, metastasis and resistance to chemotherapy. Inhibition of the Shh/Gli pathway activity/function is a potential therapeutic strategy for the treatment of lung SCC patients. PMID:24758269

  4. An Autopsy Case of Rapidly Progressing Spindle Cell Carcinoma of the Lung Accompanied with Intratumor Hemorrhage

    PubMed Central

    Kida, Jun-ichiro; Kanaji, Nobuhiro; Kishi, Sosuke; Imaida, Katsumi; Bandoh, Shuji

    2015-01-01

    Patient: Male, 74 Final Diagnosis: Spindle cell carcinoma of the lung Symptoms: — Medication: Pemetrexed • carboplatin Clinical Procedure: Biopsy and autopsy Specialty: Oncology Objective: Rare disease Background: Spindle cell carcinoma (SPCC) of the lung is a subset of sarcomatoid carcinoma. Its clinical features are unclear because of its rarity. Here, we report an autopsy case of SPCC and review CT findings and chemotherapeutic regimens based on previous reports of this disease. To our knowledge, this is the first reported case of pemetrexed used to treat SPCC. Case Report: A 74-year-old Japanese male presented with dyspnea and contrast-enhanced computed tomography (CT) showed abundant left pleural effusion and a mass in lower lobe of the left lung. By the tumor biopsy, he was diagnosed for SPCC of the lung, cT3N0M1a, stage IV. The tumor was resistant to chemotherapy with carboplatin and pemetrexed, and rapidly progressed. Autopsy revealed abundant hemorrhage within the tumor, which apparently reflects a low-density area in CT. Conclusions: Present case and the accumulation of cases indicate that low-density areas in CT and rapid tumor progression may be common SPCC findings. PMID:26558362

  5. A rare case of non-small cell carcinoma of lung presenting as miliary mottling.

    PubMed

    Jayaram Subhashchandra, Ballaekere; Ismailkhan, Mohammed; Chikkaveeraiah Shashidhar, Kuppegala; Gopalakrishna Narahari, Moda

    2013-03-01

    Miliary mottling on chest radiography is seen in miliary tuberculosis, certain fungal infections, sarcoidosis, coal miner's pneumoconiosis, silicosis, hemosiderosis, fibrosing alveolitis, acute extrinsic allergic alveolitis, pulmonary eosinophilic syndrome, pulmonary alveolar proteinosis, and rarely in hematogenous metastases from the primary cancers of the thyroid, kidney, trophoblasts, and some sarcomas. Although very infrequent, miliary mottling can be seen in primary lung cancers. Herein, we report the case of a 28-year-old female with chest X-ray showing miliary mottling. Thoracic computed tomography (CT) features were suggestive of tuberculoma with miliary tuberculosis. CT-guided fine needle aspiration cytology confirmed the diagnosis as lower-lobe, left lung non-small cell carcinoma (adenocarcinoma). It is rare for the non-small cell carcinoma of the lung to present as miliary mottling. The rarity of our case lies in the fact that a young, non-smoking female with miliary mottling was diagnosed with non-small cell carcinoma of the lung. PMID:23645961

  6. Carcinoma of the lung in Ontario gold miners: possible aetiological factors.

    PubMed Central

    Kusiak, R A; Springer, J; Ritchie, A C; Muller, J

    1991-01-01

    A cohort of 54,128 men who worked in Ontario mines was observed for mortality between 1955 and 1986. Most of these men worked in nickel, gold, or uranium mines; a few worked in silver, iron, lead/zinc, or other ore mines. If mortality that occurred after a man had started to mine uranium was excluded, an excess of carcinoma of the lung was found among the 13,603 Ontario gold miners in the study (standardised mortality ratio (SMR) 129, 95% confidence interval (95% CI) 115-145) and in men who began to mine nickel before 1936 (SMR 141, 95% CI 105-184). The excess mortality from lung cancer in the gold miners was confined to men who began gold mining before 1946. No increase in the mortality from carcinoma of the lung was evident in men who began mining gold after the end of 1945, in men who began mining nickel after 1936, or in men who mined ores other than gold, nickel, and uranium. In the gold mines each year of employment before the end of 1945 was associated with a 6.5% increase in mortality from lung cancer 20 or more years after the miner began working the mines (95% CI 1.6-11.4%); each year of employment before the end of 1945 in mines in which the host rock contained 0.1% arsenic was associated with a 3.1% increase in lung cancer 20 years or more after exposure began (95% CI 1.1-5.1%); and each working level month of exposure to radon decay products was associated with a 1.2% increase in mortality from lung cancer five or more years after exposure began (95% CI 0.02-2.4%). A comparison of two models shows that the excess of lung cancer mortality in Ontario gold miners is associated with exposure to high dust concentrations before 1946, with exposure to arsenic before 1946, and with exposure to radon decay products. No association between the increased incidence of carcinoma of the lung in Ontario gold miners and exposure to mineral fibre could be detected. It is concluded that the excess of carcinoma of the lung in Ontario gold miners is probably due to

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

    PubMed Central

    Falkenstern-Ge, R. F.; Bode-Erdmann, S.; Ott, G.; Wohlleber, M.; Kohlhäufl, M.

    2013-01-01

    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. PMID:23710393

  8. ‘Dancing eyes, dancing feet syndrome’ in small cell lung carcinoma

    PubMed Central

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

    2014-01-01

    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. PMID:24759364

  9. Amplification of FGFR1 gene and expression of FGFR1 protein is found in different histological types of lung carcinoma.

    PubMed

    Sousa, Vitor; Reis, Diana; Silva, Maria; Alarcão, Ana Maria; Ladeirinha, Ana Filipa; d'Aguiar, Maria João; Ferreira, Teresa; Caramujo-Balseiro, Sandra; Carvalho, Lina

    2016-08-01

    Although lung cancer continues to be the leading cause of cancer-related death, accurate diagnosis followed by personalized treatment is expected to raise the 5-year survival rate. Targeted therapies are now in routine clinical use, in particular for lung adenocarcinoma (ADC). Fibroblast growth factor receptor 1 (FGFR1) has recently emerged as a molecular target, especially in squamous cell/epidermoid carcinoma (SQC) of the lung. This paper evaluates FGFR1 expression and gene copy number in adenocarcinomas, squamous cell carcinomas, pleomorphic carcinomas (PLEOMC) and adenosquamous carcinomas (ADSQC) of the lung and also explores the epithelial-mesenchymal transition (EMT) pathway. We studied 76 lung carcinomas: 34 ADC, 24 SQC, 10 PLEOMC and 8 ADSQC. FGFR1 expression was evaluated by immunohistochemistry and gene amplification by fluorescence in situ hybridization (FISH). Higher FGFR1 protein expression was observed in all tumour types compared to non-tumour tissue. FGFR1 expression was higher in ADC and PLEOMC than in SQC. We found a tendency to higher expression in ADC than in SQC and significantly higher expression in PLEOMC than in other histological subtypes. FISH-based amplification of FGFR1 was identified in 15 (20 %) lung carcinomas: 5 (15 %) ADC, 5 (21 %) SQC, 3 (30 %) PLEOMC and 2 (25 %) ADSQC. Amplification was more frequent in SQC without significant differences. FGFR1 protein is expressed in the majority of lung carcinomas, though it is higher in ADC and PLEOMC (the latter may reflect the importance of FGFR1 control of the EMT pathway). FGFR1 amplification was identified in all types of lung carcinoma. Although FGFR1 is most frequently amplified in SQC, other histological types merit assessment of FGFR1 amplification, in order to select patients that might benefit from targeted therapy. PMID:27194548

  10. Proliferative potential and p53 overexpression in precursor and early stage lesions of bronchioloalveolar lung carcinoma.

    PubMed Central

    Kitamura, H.; Kameda, Y.; Nakamura, N.; Nakatani, Y.; Inayama, Y.; Iida, M.; Noda, K.; Ogawa, N.; Shibagaki, T.; Kanisawa, M.

    1995-01-01

    To elucidate the pathogenesis of bronchioloalveolar lung carcinoma (BAC), we evaluated the lesion size, growth fraction, and p53 overexpression of atypical adenomatous hyperplasia (AAH) and early stage BAC. AAH was classified as showing low grade or high grade atypia. AAH-like carcinoma, presumably very early stage BAC, was distinguished from AAH in that it exhibited remarkable atypia suggestive of malignant potential and from overt BAC in that it lacked unequivocal malignant features, including invasive/destructive growth. The growth fraction was determined immunohistochemically in terms of the Ki-67 labeling index. The overexpression of p53 was evaluated by assessing the nuclear accumulation of immunoreactive p53 protein. Both the lesion size and the growth fraction increased from low grade AAH, to high grade AAH, to AAH-like carcinoma, and to overt adenocarcinoma. The overexpression of p53 in AAH-like carcinoma was similar to that in overt adenocarcinoma and was more frequent than that in AAH. Our findings indicate that AAH, AAH-like carcinoma, and overt BAC represent different categories, although the cellular events occurring in these lesions presumably represent a continuous spectrum of the changes that are reflected in the cytomorphology and lesion size. The findings here suggest that AAH and AAH-like carcinomas constitute a population of heterogeneous lesions representing different steps toward overt BAC. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:7717455

  11. [Sweetness dysgeusia in a case of SIADH caused by lung carcinoma].

    PubMed

    Nakazato, Yoshihiko; Abe, Tatsuya; Tamura, Naotoshi; Shimazu, Kunio

    2006-06-01

    A 56-year-old woman, with dysgeusia in which nearly all food was felt as sweet, was admitted to our hospital seeking for treatment. Serum sodium concentration was 113 mmol/L, but serum creatinine, zinc, urea nitrogen, and potassium, as well as blood glucose, were all within normal ranges. Dysgeusia disappeared when serum sodium level was normalized, but recurred when hyponatremia relapsed. She was diagnosed as having large cell lung carcinoma. We considered that the cause of hyponatremia was inappropriate secretion of antidiuretic hormone (SIADH) due to lung carcinoma. Miraculin is one of taste-modifying substances which fits the sweet receptor site and induces a strong sweet taste. We considered that taste-modifying substances same as miraclin are involved in the pathophysiology of this disease. PMID:16986705

  12. Carcinoma of Lung with Adrenal Hyperfunction and Hypercalcemia Treated by Parathyroidectomy

    PubMed Central

    Gault, M. Henry; Kinsella, T. Douglas

    1965-01-01

    A case of severe hypercalcemia secondary to carcinoma of the lung is described in which hypokalemic alkalosis, renal failure and pancreatitis were also present. The relative importance of the few bone metastases found at autopsy is considered, and a probable endocrine-like effect of the tumour in the development of the hypercalcemia is postulated. Treatment of the hypercalcemia included administration of corticosteroids and disodium EDTA, peritoneal dialysis and subtotal parathyroidectomy; the most effective of these was peritoneal dialysis. Subtotal parathyroidectomy failed to produce a further decrease in serum calcium values. The occurrence of hypokalemic alkalosis in the presence of increased adrenocortical function and its relationship to the carcinoma of the lung are discussed. The possibility that this neoplasm produced two factors which caused systemic effects ordinarily associated with the function of endocrine glands must be considered. PMID:14243867

  13. Identification of potential erythrocyte phospholipid fatty acid biomarkers of advanced lung adenocarcinoma, squamous cell lung carcinoma, and small cell lung cancer.

    PubMed

    Sánchez-Rodríguez, Patricia; Rodríguez, Marina C; Sánchez-Yagüe, Jesús

    2015-07-01

    New biomarkers for lung cancer would be valuable. Our aim was to analyze the fatty acid profiles of the main phospholipid species in erythrocytes from patients with advanced squamous cell lung carcinoma (SCC), lung adenocarcinoma (ADC), and small cell lung cancer (SCLC) and benign lung diseases (chronic obstructive pulmonary disease (COPD) and asthma) to determine the fatty acids that could be use as lung cancer markers. Twenty-eight, 18, 14, 16, and 15 patients with, respectively, SCC, ADC, SCLC, asthma, and COPD and 50 healthy subjects were enrolled in the study. Fatty acid profiles were investigated using gas chromatography/mass spectrometry followed by receiver operating characteristic (ROC) curve analysis. The fatty acid profiles changed significantly in the different pathologies analyzed. Based on the diagnostic yields and operating characteristics, the most significant fatty acids that might be used as biomarkers were as follows: ADC--arachidonic acid (20:4n6) in phosphatidylcholine and oleic acid (18:1n9) in phosphatidylethanolamine (PE); SCC--eicosapentaenoic acid (20:5n3) in PE and palmitic acid (16:0) in phosphatidylserine + phosphatidylinositol (PS+PI); SCLC--eicosadienoic acid (20:2n6) in PS+PI and lignoceric acid (24:0) in sphingomyelin. In conclusion, fatty acids from erythrocyte phospholipid species might serve as biomarkers in the diagnosis, and probably in other aspects related to clinical disease management, of ADC, SCC, and SCLC. PMID:25702090

  14. Identification of somatic mutations in non-small cell lung carcinomas using whole-exome sequencing.

    PubMed

    Liu, Pengyuan; Morrison, Carl; Wang, Liang; Xiong, Donghai; Vedell, Peter; Cui, Peng; Hua, Xing; Ding, Feng; Lu, Yan; James, Michael; Ebben, John D; Xu, Haiming; Adjei, Alex A; Head, Karen; Andrae, Jaime W; Tschannen, Michael R; Jacob, Howard; Pan, Jing; Zhang, Qi; Van den Bergh, Francoise; Xiao, Haijie; Lo, Ken C; Patel, Jigar; Richmond, Todd; Watt, Mary-Anne; Albert, Thomas; Selzer, Rebecca; Anderson, Marshall; Wang, Jiang; Wang, Yian; Starnes, Sandra; Yang, Ping; You, Ming

    2012-07-01

    Lung cancer is the leading cause of cancer-related death, with non-small cell lung cancer (NSCLC) being the predominant form of the disease. Most lung cancer is caused by the accumulation of genomic alterations due to tobacco exposure. To uncover its mutational landscape, we performed whole-exome sequencing in 31 NSCLCs and their matched normal tissue samples. We identified both common and unique mutation spectra and pathway activation in lung adenocarcinomas and squamous cell carcinomas, two major histologies in NSCLC. In addition to identifying previously known lung cancer genes (TP53, KRAS, EGFR, CDKN2A and RB1), the analysis revealed many genes not previously implicated in this malignancy. Notably, a novel gene CSMD3 was identified as the second most frequently mutated gene (next to TP53) in lung cancer. We further demonstrated that loss of CSMD3 results in increased proliferation of airway epithelial cells. The study provides unprecedented insights into mutational processes, cellular pathways and gene networks associated with lung cancer. Of potential immediate clinical relevance, several highly mutated genes identified in our study are promising druggable targets in cancer therapy including ALK, CTNNA3, DCC, MLL3, PCDHIIX, PIK3C2B, PIK3CG and ROCK2. PMID:22510280

  15. Locally extensive angio-invasive Scedosporium prolificans infection following resection for squamous cell lung carcinoma

    PubMed Central

    Holmes, Natasha E.; Trevillyan, Janine M.; Kidd, Sarah E.; Leong, Trishe Y.-M.

    2013-01-01

    We report a case of Scedosporium prolificans infection in a patient following surgery for squamous cell lung carcinoma. Combination therapy with voriconazole and terbinafine was commenced for intrathoracic infection and mycotic vasculitis. In spite of antifungal treatment, he developed culture-positive sternal and rib osteomyelitis four months later. Scedosporiosis is not commonly reported in patients with solid organ malignancies, and this case highlights its aggressive nature and propensity for direct local invasion. PMID:24432228

  16. Anaplastic lymphoma kinase-positive squamous cell carcinoma of the lung: A case report

    PubMed Central

    YAMAMOTO, YOKO; KODAMA, KEN; MANIWA, TOMOHIRO; TAKEDA, MASASHI; KISHIMA, HIROKI

    2016-01-01

    It is widely known that echinoderm microtubule-associated protein-like 4 anaplastic lymphoma kinase (EML4-ALK) rearrangement mostly occurs in the adenocarcinoma subtype of non-small-cell lung cancer (NSCLC). Patients with squamous cell carcinoma harboring the ALK rearrangement are extremely rare. This is a case report of a squamous cell carcinoma patient with EML4-ALK rearrangement. An elderly man with a heavy smoking history presented with a mass lesion in the right main bronchus. Bronchoscopic biopsy of the tumor confirmed a diagnosis of squamous cell carcinoma, and it was proven to harbor ALK rearrangement, based on fluorescence in situ hybridization, but not epidermal growth factor receptor mutations. The patient underwent radiation therapy, with a markedly favorable response. ALK-targeted treatment may be a viable option if disease progression occurs in such a case in the future. PMID:27330767

  17. Bone marrow-derived cells contribute to NDEA-induced lung squamous cell carcinoma.

    PubMed

    Luo, Dan; Liu, Dengqun; Zhou, Xiangdong; Yang, Shiming; Tang, Chunlan; Liu, Guoxiang

    2013-02-01

    Bone marrow-derived stem cells (BMDCs) have the ability to differentiate into lung epithelial cells in response to damage; however, their role in squamous cell carcinoma (SCC) formation is unknown. This study aimed to determine whether BMDC-derived lung epithelial cells could contribute to SCC formation. A model of lung SCC induced with N-nitrosodiethylamine (NDEA) in recipient female mice transplanted with green fluorescent protein (GFP)-positive BMDCs from male donors was established. Incorporation of BMDCs in lung tissue was determined using immunohistochemistry and immunofluorescence to detect GFP expression and fluorescence in situ hybridization to Y chromosomes. BMDC appeared at three stages of lung SCC progression: metaplasia, dysplasia, and carcinoma. There was a significantly higher proportion of GFP-positive (GFP(+)) cells within SCC than was found in metaplasia and dysplasia 16 weeks post-transplantation (both P < 0.017); GFP(+) BMDCs were also observed in clusters within several SCC nests. Furthermore, most GFP(+) cells in SCC were pancytokeratin-positive (PCK(+)) epithelial cells, and some exhibited proliferative activity as determined by Ki67 staining (9.7 ± 3.92 %). The presence of GFP(+)Ki67(+)PCK(+) cells within SCC nests suggested that some donor BMDCs differentiated into proliferating epithelial cells. Finally, analysis of p63 expression, a marker of SCC cells, indicated that the presence of GFP(+)p63(+) cells (green) in inner parts of the SCC. These findings strongly suggest that BMDC-derived lung epithelial cells could participate in lung SCC formation and partially contribute to tumor growth, which might have significant potential implications for both clinical cancer therapy using BMDCs. PMID:23055190

  18. Primary adrenal sarcomatoid carcinoma metastatic to the lung: Case report and review of the literature

    PubMed Central

    ZHU, CHUANGZHI; ZHENG, AIPING; MAO, XIANGMING; SHI, BENTAO; LI, XIANXIN

    2016-01-01

    Adrenal sarcomatoid carcinoma is a rare adrenal carcinoma. To the best of our knowledge, only 11 cases have been reported since 1987. Adrenal sarcomatoid carcinoma presents a diagnostic challenge due to its atypical symptoms and histological patterns. At the time of diagnosis, a large percentage of patients are already at the metastatic stage and succumb within a few months. The present study reports a case of a 59-year-old man presenting with asthenia and weight loss with adrenal sarcomatoid carcinoma metastatic to the lung. A computed tomography (CT) scan and ultrasonography of the patient's abdomen suggested a large homogeneous mass in the right adrenal gland, and a CT scan of his chest suggested lung metastasis. Right adrenalectomy was performed. Histological examination revealed that the tumor was composed of sarcomatous and carcinomatous differentiation elements. Immunohistochemical examination revealed tumor cell positivity for vimentin and cytokeratin. At the 6-month follow-up the patient exhibited no disease progression and refused further proposed treatment. The patient was alive at the time of writing the current report. The present case report additionally reviews the literature, for the purpose of raising awareness of these rare lesions and assisting in achieving accurate diagnoses and effective treatment. PMID:27123074

  19. Spinal cord metastasis in small cell carcinoma of the lung

    SciTech Connect

    Holoye, P.; Libnoch, J.; Cox, J.; Kun, L.; Byhardt, R.; Almagro, U.; McCelland, S.; Chintapali, K.

    1984-03-01

    Among 50 patients with small cell bronchogenic carcinoma who were placed on a protocol of combined chemotherapy and radiation therapy, seven patients developed recurrence in the spinal cord. Five cases terminated in paraplegia and death. One patient with pontine recurrence recovered with local radiation therapy. One patient, diagnosed early, responded to local radiation therapy and is ambulatory. Methods of diagnosis were myelogram, computerized axial tomography, cerebro spinal fluid, chemistry and cytologies. The poor prognosis and the difficulty of diagnosis suggest that prophylactic therapy of the entire cranio-spinal axis should be evaluated.

  20. High-fat diet enhances and plasminogen activator inhibitor-1 deficiency attenuates bone loss in mice with Lewis Lung carcinoma

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study determined the effects of a high-fat diet and plasminogen activator inhibitor-1 deficiency (PAI-1-/-) on bone structure in mice bearing Lewis lung carcinoma (LLC) in lungs. Reduction in bone volume fraction (BV/TV) by 22% and 21%, trabecular number (Tb.N) by 8% and 4% and bone mineral de...

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

    PubMed

    Rocha, Cláudia M; Barros, António S; Goodfellow, Brian J; Carreira, Isabel M; Gomes, Ana; Sousa, Vitor; Bernardo, João; Carvalho, Lina; Gil, Ana M; Duarte, Iola F

    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 tissues from 56 patients undergoing surgical excision of primary lung carcinomas. Multivariate modeling allowed tumour and control tissues to be discriminated with high accuracy (97% classification rate), mainly due to significant differences in the levels of 13 metabolites. Notably, the magnitude of those differences were clearly distinct for AdC and SqCC: major alterations in AdC were related to phospholipid metabolism (increased phosphocholine, glycerophosphocholine and phosphoethanolamine, together with decreased acetate) and protein catabolism (increased peptide moieties), whereas SqCC had stronger glycolytic and glutaminolytic profiles (negatively correlated variations in glucose and lactate and positively correlated increases in glutamate and alanine). Other tumour metabolic features were increased creatine, glutathione, taurine and uridine nucleotides, the first two being especially prominent in SqCC and the latter in AdC. Furthermore, multivariate analysis of AdC and SqCC profiles allowed their discrimination with a 94% classification rate, thus showing great potential for aiding lung tumours subtyping. Overall, this study has provided new, clear evidence of distinct metabolic signatures for lung AdC and SqCC, which can potentially impact on diagnosis and provide important leads for future research on novel therapeutic targets or imaging tracers. PMID:25368033

  2. Chlorin e6 – polyvinylpyrrolidone mediated photosensitization is effective against human non-small cell lung carcinoma compared to small cell lung carcinoma xenografts

    PubMed Central

    Chin, William WL; Heng, Paul WS; Olivo, Malini

    2007-01-01

    Background Photodynamic therapy (PDT) is an effective local cancer treatment that involves light activation of a photosensitizer, resulting in oxygen-dependent, free radical-mediated cell death. Little is known about the comparative efficacy of PDT in treating non-small cell lung carcinoma (NSCLC) and small cell lung carcinoma (SCLC), despite ongoing clinical trials treating lung cancers. The present study evaluated the potential use of chlorin e6 – polyvinylpyrrolidone (Ce6-PVP) as a multimodality photosensitizer for fluorescence detection and photodynamic therapy (PDT) on NSCLC and SCLC xenografts. Results Human NSCLC (NCI-H460) and SCLC (NCI-H526) tumor cell lines were used to establish tumor xenografts in the chick chorioallantoic membrane (CAM) model as well as in the Balb/c nude mice. In the CAM model, Ce6-PVP was applied topically (1.0 mg/kg) and fluorescence intensity was charted at various time points. Tumor-bearing mice were given intravenous administration of Ce6-PVP (2.0 mg/kg) and laser irradiation at 665 nm (fluence of 150 J/cm2 and fluence rate of 125 mW/cm2). Tumor response was evaluated at 48 h post PDT. Studies of temporal fluorescence pharmacokinetics in CAM tumor xenografts showed that Ce6-PVP has a selective localization and a good accuracy in demarcating NSCLC compared to SCLC from normal surrounding CAM after 3 h post drug administration. Irradiation at 3 h drug-light interval showed greater tumor necrosis against human NSCLC xenografts in nude mice. SCLC xenografts were observed to express resistance to photosensitization with Ce6-PVP. Conclusion The formulation of Ce6-PVP is distinctly advantageous as a diagnostic and therapeutic agent for fluorescence diagnosis and PDT of NSCLC. PMID:18053148

  3. [Effects of ethanol on metastasis of Lewis lung carcinoma in male mice with different social states].

    PubMed

    Il'nitskaia, S I; Nikolin, V P; Popova, N A; Avgustinovich, D F; Kaledin, V I; Kudriavtseva, N N

    2009-01-01

    The aim of this work was to study the effect of ethanol on experimental metastasis of Lewis lung carcinoma in male mice in positive or negative emotional states. Sensory contact model was used for generating animals with repeated experience of social victories or defeats. Tumor cells were injected into the tail vein after 20 days of agonistic interactions, and the number of metastases in the lung was calculated 16 days later. Group-housed mice were used as the controls. Mice of all experimental groups were chronically treated with ethanol (20%, 2 ml/kg of weight, i.p.) and saline during 7 days starting with the day of tumor cells injections. The experimental metastasis was shown to develop differently in mice with opposing social experience: saline-treated winners had significantly less metastases in the lung than the saline-treated losers. Chronic ethanol injections decreased the number of metastases in the losers, increased it in the winners and did not affect the controls. The results obtained indicate that effects if ethanol on Lewis lung carcinoma metastasis depend on psychoemotional status in male mice. PMID:19323446

  4. Molecular genetics and mechanisms of apoptosis in carcinomas of the lung and pleura: therapeutic targets.

    PubMed

    Motadi, L R; Misso, N L; Dlamini, Z; Bhoola, K D

    2007-12-20

    Cancers of the lung and pleura remain a major cause of cancer deaths, both in men and women, with strong causal relationships between cigarette smoking and asbestos fibres, and deaths from lung cancer and mesothelioma, respectively. The poor survival rates for small cell lung cancer and mesotheliomas argue powerfully for greater understanding of mechanisms of carcinogenesis, genetic abnormalities and the role of tumour suppressor genes and proteins in carcinomas of the lung and pleura. Despite progress in the development of newer cytotoxic drugs, lung cancer remains a lethal disease. Chemotherapy and radiotherapy produce only a modest improvement in survival of patients with advanced disease. Increased knowledge of molecular mechanisms of lung cancer and apoptosis are providing opportunities for treating lung cancer with new classes of molecularly targeted drugs. These novel therapies should target the abnormalities in lung cancer by maximizing the effects of anti-tumour molecules, with minimal side effects on normal tissues. Of the several molecular targets, those receiving attention are p53 gene replacement, Bcl-2 downregulation, apoptosis by induced by TNF, the FAS/CD95 receptor system and TRAIL, and inhibition of NF-kappaB. Although several studies have shown benefits, there is a need for well planned clinical trials of drugs that target the apoptotic cascade. Stem cell therapy and gene replacement offer the prospect of novel approaches that are likely in the near future to play a definitive role in the treatment of advanced lung cancer. Furthermore, with their apparent minimal toxicity to normal tissues, the newer molecular targets represent attractive investigational directions for innovative cancer therapies. PMID:18039530

  5. Treatment of advanced squamous cell carcinoma of the lung: a review

    PubMed Central

    Mileham, Kathryn F.; Bonomi, Philip D.; Batus, Marta; Fidler, Mary J.

    2015-01-01

    Lung cancer remains the single deadliest cancer both in the US and worldwide. The great majority of squamous cell carcinoma (SCC) is attributed to cigarette smoking, which fortunately is declining alongside cancer incidence. While we have been at a therapeutic plateau for advanced squamous cell lung cancer patients for several decades, recent observations suggest that we are on the verge of seeing incremental survival improvements for this relatively large group of patients. Current studies have confirmed an expanding role for immunotherapy [including programmed cell death-1 (PD-1)/programmed cell death ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibition], a potential opportunity for VEGFR inhibition, and even future targets in fibroblast growth factor receptor (FGFR) and PI3K-AKT that collectively should improve survival as well as quality of life for those affected by squamous cell lung cancer over the next decade. PMID:26629421

  6. Current Concepts on the Molecular Pathology of Non-small Cell Lung Carcinoma

    PubMed Central

    Fujimoto, Junya; Wistuba, Ignacio I.

    2014-01-01

    Recent advances in the understanding of the complex biology of non-small cell lung carcinoma (NSCLC), particularly activation of oncogenes by mutation, translocation and amplification, have provided new treatment targets for this disease, and allowed the identification of subsets of NSCLC tumors, mostly with adenocarcinoma histology, having unique molecular profiles that can predict response to targeted therapy. The identification of a specific genetic and molecular targetable abnormalities using tumor tissue and cytology specimens followed by the administration of a specific inhibitor to the target, are the basis of personalized lung cancer treatment. In this new paradigm, the role of a precise pathology diagnosis of lung cancer and the proper handling of tissue and cytology samples for molecular testing is becoming increasingly important. These changes have posed multiple new challenges for pathologists to adequately integrate routine histopathology analysis and molecular testing into the clinical pathology practice for tumor diagnosis and subsequent selection of the most appropriate therapy. PMID:25239274

  7. [Immunohistochemical description of proliferative activity and apoptosis of lung squamous cell carcinoma (literature review)].

    PubMed

    Филенко, Борис Н; Ройко, Наталия В; Степанчук, Алла П; Проскурня, Сергей А

    2016-01-01

    The analysis of the publications are describe immunohistochemical study of proliferative activity and apoptosis of lung squamous cell carcinoma. Established that the imbalance between proliferation and cell death is a key process in the development of tumors. However, the value of tumor markers in histogenesis and morfogenesis of tumors and forecast their occurrence is not studied enough. Despite the significant amount of scientific literature devoted to this issue, has not yet established a clear link expression of immunohistochemical markers of proliferation and apoptosis with the degree of differentiation of squamous cell lung cancer. Analysis of the literature shows that the morphology of this histogenetics type lung cancer at the cellular, subcellular structural and functional levels are controversial and require detailed investigation. PMID:27487551

  8. Progression after spontaneous regression in lung large cell neuroendocrine carcinoma: Report of a curative resection.

    PubMed

    Tomizawa, Kenji; Suda, Kenichi; Takemoto, Toshiki; Iwasaki, Takuya; Sakaguchi, Masahiro; Kuwano, Hiroyuki; Mitsudomi, Tetsuya

    2015-09-01

    We present the first reported case of lung large cell neuroendocrine carcinoma (LCNEC) with spontaneous regression followed by progression. An 85-year-old woman presented with a 2.8-cm nodule in the right upper lung lobe on chest computed tomography. After four months, the tumor decreased to 1.8 cm and remained unchanged in size for the next three months, but it grew to 8.6 cm and invaded the mediastinal fat tissue after approximately one year. Ultrasound echo-guided percutaneous biopsy revealed the tumor to be LCNEC. The patient underwent a right upper lobectomy with lymph node dissection. She had a good postoperative course with no complications. Physicians and surgeons should be aware that radiographic regression of a pulmonary nodule does not necessarily exclude the possibility of lung cancer. PMID:26443884

  9. Progression after spontaneous regression in lung large cell neuroendocrine carcinoma: Report of a curative resection

    PubMed Central

    Tomizawa, Kenji; Suda, Kenichi; Takemoto, Toshiki; Iwasaki, Takuya; Sakaguchi, Masahiro; Kuwano, Hiroyuki; Mitsudomi, Tetsuya

    2015-01-01

    We present the first reported case of lung large cell neuroendocrine carcinoma (LCNEC) with spontaneous regression followed by progression. An 85-year-old woman presented with a 2.8-cm nodule in the right upper lung lobe on chest computed tomography. After four months, the tumor decreased to 1.8 cm and remained unchanged in size for the next three months, but it grew to 8.6 cm and invaded the mediastinal fat tissue after approximately one year. Ultrasound echo-guided percutaneous biopsy revealed the tumor to be LCNEC. The patient underwent a right upper lobectomy with lymph node dissection. She had a good postoperative course with no complications. Physicians and surgeons should be aware that radiographic regression of a pulmonary nodule does not necessarily exclude the possibility of lung cancer. PMID:26443884

  10. Identification of proteomic differences between squamous cell carcinoma of the lung and bronchial epithelium.

    PubMed

    Poschmann, Gereon; Sitek, Barbara; Sipos, Bence; Ulrich, Anna; Wiese, Sebastian; Stephan, Christian; Warscheid, Bettina; Klöppel, Günter; Vander Borght, Ann; Ramaekers, Frans C S; Meyer, Helmut E; Stühler, Kai

    2009-05-01

    Proteins that exhibit different expression levels in normal and malignant lung cells are good candidate biomarkers to improve early diagnosis and intervention. We used a quantitative approach and compared the proteome of microdissected cells from normal human bronchial epithelium and squamous cell carcinoma tumors of histopathological grades G2 and G3. DIGE analysis and subsequent MS-based protein identification revealed that 32 non-redundant proteins were differentially regulated between the respective tissue types. These proteins are mainly involved in energy pathways, cell growth or maintenance mechanisms, protein metabolism, and the regulation of DNA and RNA metabolism. The expression of some of these proteins was analyzed by immunohistochemistry using tissue microarrays containing tissue specimen of 55 patients, including normal bronchial epithelium, squamous cell carcinomas, adenocarcinomas, and large cell carcinomas. The results of the immunohistochemical studies correlated with the proteome study data and revealed that particularly HSP47 and a group of cytokeratins (i.e. cytokeratins 6a, 16, and 17) are significantly co-regulated in squamous cell carcinoma. Furthermore cytokeratin 17 showed significantly higher abundance in G2 grade compared with G3 grade squamous cell carcinomas in both the gel-based and the immunohistochemical analysis. Therefore this protein might be used as a marker for stratification between different tumor grades. PMID:19176476

  11. Lobar lung transplantation--is it comparable with standard lung transplantation?

    PubMed

    Slama, Alexis; Ghanim, Bahil; Klikovits, Thomas; Scheed, Axel; Hoda, Mir A; Hoetzenecker, Konrad; Jaksch, Peter; Matilla, Jose; Taghavi, Sharokh; Klepetko, Walter; Aigner, Clemens

    2014-09-01

    Lobar lung transplantation is used mainly for urgent small recipients who are less likely to obtain size matched lungs in due time. Only limited numbers have been published, and we herewith report the largest series of lobar-LuTX. We analyzed our LuTX database from 1/2001 to 12/2012 and compared the outcome of lobar-LuTX recipients with those receiving standard LuTX. Seven hundred and seventy-eighty LuTX (group 1) were performed either in standard technique by implanting the whole lungs (n = 539) or with downsizing by wedge resection of the right middle lobe and/or the left lingula (n = 239). One hundred and thirty-eight LuTX were performed in lobar technique (group 2) to overcome more pronounced size discrepancies. Patients in group 1 had a different spectrum of diagnoses and were less frequently bridged to LuTX (P < 0.001). Intubation time, ICU stay, and hospital stay were shorter in group 1 (P < 0.001). One-year survival was 84.8% vs. 65.1%, and 5-years survival 69.9% vs. 54.9% (P < 0.001). In multivariate analyzes, procedure, diagnosis, and pre-operative bridging were shown to be significant prognostic factors in survival. Early postoperative outcome in Lobar LuTX was significantly inferior to standard LuTX recipients. However, survival rates of successfully dismissed patients were comparable with standard LuTX (P = 0.168); thereby, Lobar-LuTX remains an important option in the management of urgent small recipients. PMID:24810771

  12. A rare case of lung carcinoma with mucoepidermoid histopathology: a case report and review of the literature.

    PubMed

    Thomas, David; Modi, Yashpal; Dorai, Bhuvaneswari; Guron, Gunwant

    2015-01-01

    Mucoepidermoid carcinoma of the lung is exceedingly rare. Our case involves a 58-year-old male who presented with shortness of breath, dysphagia, and weight loss. He denied ever smoking. Chest x-ray revealed trapped lung, and CT demonstrated a right bronchial mass. Diagnosis of lung carcinoma was made by bronchoscopic FNA biopsy. EGFR mutation was negative. Staging workup demonstrated evidence of advanced disease. Performance status was good, and it was decided to start chemotherapy and radiation for palliation. Lung carcinomas often present as an obstructing hilar mass. There are different histological grades that affect progression and survival. Though uncommon, metastatic spread has been previously reported. Studies have investigated the possible role of tyrosine kinase inhibitors in both EGFR-mutated and non-mutated cases. Unfortunately, there has been little consensus as to which therapies are most beneficial. PMID:25887880

  13. Management of EGFR mutated nonsmall cell lung carcinoma patients.

    PubMed

    Grigoriu, Bogdan; Berghmans, Thierry; Meert, Anne-Pascale

    2015-04-01

    Tyrosine kinase inhibitors (TKIs) targeting the epidermal growth factor receptor (EGFR) are common in the therapeutic armentarium of lung cancer today. Initially tested in an unselected population, they have been of limited usefulness until the identification EGFR gene mutations. Activating mutations generate conformational changes that result in a shift toward an active state of the catalytic domain and are associated with sensitivity to first generation EGFR TKI. Other mutations have been associated with resistance to these drugs, but for rare mutations there is limited data concerning their role in predicting response to EGFR TKI. To date, four molecules have been approved for the treatment of EGFR mutated lung cancer. Gefitinib and/or erlotinib are available in almost all countries. Afatinib has been approved by the US Food and Drug Administration and by the European Medicines Agency, and icotinib has been approved only in China. Other, more active, third generation agents with a higher binding affinity for the receptor, or that are directed against specific mutations, are under development. EGFR TKIs have a favourable impact on progression-free survival when given as first line treatment in mutated patients, but may also have a moderate effect as a salvage therapy and in maintenance in an unselected population. PMID:25700389

  14. Phytoestrogen Suppresses Efflux of the Diagnostic Marker Protoporphyrin IX in Lung Carcinoma.

    PubMed

    Fujita, Hirofumi; Nagakawa, Keisuke; Kobuchi, Hirotsugu; Ogino, Tetsuya; Kondo, Yoichi; Inoue, Keiji; Shuin, Taro; Utsumi, Toshihiko; Utsumi, Kozo; Sasaki, Junzo; Ohuchi, Hideyo

    2016-04-01

    One promising method to visualize cancer cells is based on the detection of the fluorescent photosensitizer protoporphyrin IX (PpIX) synthesized from 5-aminolevulinic acid (ALA), but this method cannot be used in cancers that exhibit poor PpIX accumulation. PpIX appears to be pumped out of cancer cells by the ABC transporter G2 (ABCG2), which is associated with multidrug resistance. Genistein is a phytoestrogen that appears to competitively inhibit ABCG2 activity. Therefore, we investigated whether genistein can promote PpIX accumulation in human lung carcinoma cells. Here we report that treatment of A549 lung carcinoma cells with genistein or a specific ABCG2 inhibitor promoted ALA-mediated accumulation of PpIX by approximately 2-fold. ABCG2 depletion and overexpression studies further revealed that genistein promoted PpIX accumulation via functional repression of ABCG2. After an extended period of genistein treatment, a significant increase in PpIX accumulation was observed in A549 cells (3.7-fold) and in other cell lines. Systemic preconditioning with genistein in a mouse xenograft model of lung carcinoma resulted in a 1.8-fold increase in accumulated PpIX. Long-term genistein treatment stimulated the expression of genes encoding enzymes involved in PpIX synthesis, such as porphobilinogen deaminase, uroporphyrinogen decarboxylase, and protoporphyrinogen oxidase. Accordingly, the rate of PpIX synthesis was also accelerated by genistein pretreatment. Thus, our results suggest that genistein treatment effectively enhances ALA-induced PpIX accumulation by preventing the ABCG2-mediated efflux of PpIX from lung cancer cells and may represent a promising strategy to improve ALA-based diagnostic approaches in a broader set of malignancies. Cancer Res; 76(7); 1837-46. ©2016 AACR. PMID:26837765

  15. Radon Exposure, IL-6 Promoter Variants, and Lung Squamous Cell Carcinoma in Former Uranium Miners

    PubMed Central

    Leng, Shuguang; Thomas, Cynthia L.; Snider, Amanda M.; Picchi, Maria A.; Chen, Wenshu; Willis, Derall G.; Carr, Teara G.; Krzeminski, Jacek; Desai, Dhimant; Shantu, Amin; Lin, Yong; Jacobson, Marty R.; Belinsky, Steven A.

    2015-01-01

    Background: High radon exposure is a risk factor for squamous cell carcinoma, a major lung cancer histology observed in former uranium miners. Radon exposure can cause oxidative stress, leading to pulmonary inflammation. Interleukin-6 (IL-6) is a pro-carcinogenic inflammatory cytokine that plays a pivotal role in lung cancer development. Objectives: We assessed whether single nucleotide polymorphisms (SNPs) in the IL6 promoter are associated with lung cancer in former uranium miners with high occupational exposure to radon gas. Methods: Genetic associations were assessed in a case–control study of former uranium miners (242 cases and 336 controls). A replication study was performed using data from the Gene Environment Association Studies (GENEVA) Genome Wide Association Study (GWAS) of Lung Cancer and Smoking. Functional relevance of the SNPs was characterized using in vitro approaches. Results: We found that rs1800797 was associated with squamous cell carcinoma in miners and with a shorter time between the midpoint of the period of substantial exposure and diagnosis among the cases. Furthermore, rs1800797 was also associated with lung cancer among never smokers in the GENEVA dataset. Functional studies identified that the risk allele was associated with increased basal IL-6 mRNA level and greater promoter activity. Furthermore, fibroblasts with the risk allele showed greater induction of IL-6 secretion by hydrogen peroxide or benzo[a]pyrene diolepoxide treatments. Conclusions: An IL6 promoter variant was associated with lung cancer in uranium miners and never smokers in two external study populations. The associations are strongly supported by the functional relevance that the IL6 promoter SNP affects basal expression and carcinogen-induced IL-6 secretion. Citation: Leng S, Thomas CL, Snider AM, Picchi MA, Chen W, Willis DG, Carr TG, Krzeminski J, Desai D, Shantu A, Lin Y, Jacobson MR, Belinsky SA. 2016. Radon exposure, IL-6 promoter variants, and lung squamous

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

    NASA Astrophysics Data System (ADS)

    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 <10, 10-99, and 100+ μg/L was 0.29%, 1.07% and 3.43%, respectively. The corresponding probabilities were 7.42%, 8.99% and 17.09% for the lifetime risk of developing lung cancer. Cigarette 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 <10, 10-99 and 100+ μg/L was 1.0 (the reference group), 2.18 (0.59-8.01), and 8.71 (2.49-30.48), respectively. The corresponding figures were 1.0 (the reference group), 1.14 (0.80-1.61), 1.84 (1.28-2.65) for lung cancer. Synergistic effects on the development of urothelial carcinoma and lung cancer existed between the arsenic exposure level and cigarette smoking. It is suggested that people who have had a high exposure to arsenic in drinking water

  17. Prognosis of resected well-differentiated neuroendocrine carcinoma of the lung.

    PubMed

    Lequaglie, C; Patriarca, C; Cataldo, I; Muscolino, G; Preda, F; Ravasi, G

    1991-10-01

    Among lung tumors, well-differentiated neuroendocrine carcinomas are often misdiagnosed or may go unrecognized. Nineteen cases of well-differentiated neuroendocrine carcinoma (WDNC) were assessed at the National Cancer Institute of Milan over a ten-year period. There was only one woman and the age range was 50 to 77 years. Most of the patients were smokers (83 percent). All tumors were radically resected. There were 12 lobectomies, two sleeve-lobectomies, three bilobectomies, one pneumonectomy, and two segmentectomies (one patient had two synchronous WDNCs). There was neither operative mortality nor major complications. Sixteen tumors were stage 1, three were stage II, and one was stage IIIa. Five patients had adjuvant chemotherapy (cyclophosphamide, doxorubicin, and vincristine [CAV] regimen). One patient was given local or regional radiotherapy. In ten patients the tumors recurred, even though four had had adjuvant treatment. The brain was the first site of metastasis in seven cases. The pathologic stage seemed not to be closely related to the appearance of metastases (six patients with stage I disease had recurrences). Only two patients with recurrence were still alive 12 and 103 months after the procedure. The percentage of survival for patients with stage I disease after more than 100 months was 68 percent. WDNC is similar to small-cell lung carcinoma (SCLC) with regard to the neurotropism of metastases. Surgery is curative for more than one half of the patients with localized disease. Therefore, multimodal therapy, probably based on tumor behavior and investigations of tumor markers, is advisable. PMID:1655361

  18. Activation of the protein-tyrosine kinase associated with the bombesin receptor complex in small cell lung carcinomas

    SciTech Connect

    Gaudino, G.; Cirillo, D.; Naldini, L.; Rossino, P.; Comoglio, P.M. )

    1988-04-01

    It has been hypothesized that bombesin-like peptides produced by small cell lung carcinomas may sustain deregulated proliferation through an autocrine mechanism. The authors have shown that the neuropeptide bombesin leads to the activation of a protein-tyrosine kinase that phosphorylates a 115-kDa protein (p115) associated with the bombesin receptor complex in mouse Swiss 3T3 fibroblasts. They now report that phosphotyrosine antibodies recognize a 115-kDa protein, phosphorylated on tyrosine, in four human small cell lung carcinoma cell lines producing bombesin but not in a nonproducer variant line. p115 from detergent-treated small cell lung carcinoma cells binds to bombesin-Sepharose and can be phosphorylated on tyrosine in the presence of radiolabeled ATP and Mn{sup 2+}. As for the p115 immunoprecipitated from mouse fibroblast, the small cell lung carcinoma p115 can be phosphorylated in an immunocomplex kinase assay. However, the latter does not require the presence of exogenous bombesin for activity. Binding data, obtained by using radiolabeled ligand, suggest receptor occupancy in the cell lines producing bombesin. These observations are consistent with the hypothesis that proliferation in some human small cell lung carcinoma lines is under autocrine control, regulated through activation of bombesin receptors.

  19. Pulmonary Endpoints (Lung Carcinomas and Asbestosis) Following Inhalation Exposure to Asbestos

    PubMed Central

    Mossman, Brooke T.; Lippmann, Morton; Hesterberg, Thomas W.; Kelsey, Karl T.; Barchowsky, Aaron; Bonner, James C.

    2011-01-01

    Lung carcinomas and pulmonary fibrosis (asbestosis) occur in asbestos workers. Understanding the pathogenesis of these diseases is complicated because of potential confounding factors, such as smoking, which is not a risk factor in mesothelioma. The modes of action (MOA) of various types of asbestos in the development of lung cancers, asbestosis, and mesotheliomas appear to be different. Moreover, asbestos fibers may act differentially at various stages of these diseases, and have different potencies as compared to other naturally occurring and synthetic fibers. This literature review describes patterns of deposition and retention of various types of asbestos and other fibers after inhalation, methods of translocation within the lung, and dissolution of various fiber types in lung compartments and cells in vitro. Comprehensive dose-response studies at fiber concentrations inhaled by humans as well as bivariate size distributions (lengths and widths), types, and sources of fibers are rarely defined in published studies and are needed. Species-specific responses may occur. Mechanistic studies have some of these limitations, but have suggested that changes in gene expression (either fiber-catalyzed directly or by cell elaboration of oxidants), epigenetic changes, and receptor-mediated or other intracellular signaling cascades may play roles in various stages of the development of lung cancers or asbestosis. PMID:21534086

  20. Identification of immunohistochemical markers for distinguishing lung adenocarcinoma from squamous cell carcinoma

    PubMed Central

    Zhan, Cheng; Yan, Li; Wang, Lin; Sun, Yang; Wang, Xingxing; Lin, Zongwu; Zhang, Yongxing; Wang, Qun

    2015-01-01

    Background Immunohistochemical staining has been widely used in distinguishing lung adenocarcinoma (LUAD) from lung squamous cell carcinoma (LUSC), which is of vital importance for the diagnosis and treatment of lung cancer. Due to the lack of a comprehensive analysis of different lung cancer subtypes, there may still be undiscovered markers with higher diagnostic accuracy. Methods Herein first, we systematically analyzed high-throughput data obtained from The Cancer Genome Atlas (TCGA) database. Combining differently expressed gene screening and receiver operating characteristic (ROC) curve analysis, we attempted to identify the genes which might be suitable as immunohistochemical markers in distinguishing LUAD from LUSC. Then we detected the expression of six of these genes (MLPH, TMC5, SFTA3, DSG3, DSC3 and CALML3) in lung cancer sections using immunohistochemical staining. Results A number of genes were identified as candidate immunohistochemical markers with high sensitivity and specificity in distinguishing LUAD from LUSC. Then the staining results confirmed the potentials of the six genes (MLPH, TMC5, SFTA3, DSG3, DSC3 and CALML3) in distinguishing LUAD from LUSC, and their sensitivity and specificity were not less than many commonly used markers. Conclusions The results revealed that the six genes (MLPH, TMC5, SFTA3, DSG3, DSC3 and CALML3) might be suitable markers in distinguishing LUAD from LUSC, and also validated the feasibility of our methods for identification of candidate markers from high-throughput data. PMID:26380766

  1. A case of paraneoplastic bullous pemphigoid in association with squamous cell carcinoma of lung

    PubMed Central

    Das, A; Das, S; Das, SK; Basuthakur, S

    2015-01-01

    Bullous pemphigoid is a chronic, autoimmune, acquired subepidermal blistering disorder. It is idiopathic in origin, and mainly seen in elderly individuals. Association between bullous pemphigoid and internal malignancies is reported in the literature, but the exact causal relation is not established. Paraneoplastic bullous pemphigoid is rarely reported in lung cancers, especially in squamous cell variety. So their presence should raise the suspicion of various internal malignancies including lung cancer. It is presented mainly with tense, large blisters over the erythematous base or over normal skin. Subepidermal blisters with tissue eosinophilia are characteristic histopathological features of bullous pemphigoid. Direct immunofluorescence shows linear deposits of IgG — complement complex along the dermoepidermal junction. Conventional treatment of bullous pemphigoid along with treatment of lung cancer (surgery, chemotherapy, radiotherapy) may result in successful resolution of skin lesions. Here, we report a rare association of paraneoplastic bullous phemphigoid and squamous cell carcinoma of lung in a 76-year-old male to increase the awareness among the clinicians regarding this variety of cutaneous paraneoplastic manifestation of lung cancer. PMID:26119440

  2. Genome-wide DNA methylation profiling of non-small cell lung carcinomas

    PubMed Central

    2012-01-01

    Background Non-small cell lung carcinoma (NSCLC) is a complex malignancy that owing to its heterogeneity and poor prognosis poses many challenges to diagnosis, prognosis and patient treatment. DNA methylation is an important mechanism of epigenetic regulation involved in normal development and cancer. It is a very stable and specific modification and therefore in principle a very suitable marker for epigenetic phenotyping of tumors. Here we present a genome-wide DNA methylation analysis of NSCLC samples and paired lung tissues, where we combine MethylCap and next generation sequencing (MethylCap-seq) to provide comprehensive DNA methylation maps of the tumor and paired lung samples. The MethylCap-seq data were validated by bisulfite sequencing and methyl-specific polymerase chain reaction of selected regions. Results Analysis of the MethylCap-seq data revealed a strong positive correlation between replicate experiments and between paired tumor/lung samples. We identified 57 differentially methylated regions (DMRs) present in all NSCLC tumors analyzed by MethylCap-seq. While hypomethylated DMRs did not correlate to any particular functional category of genes, the hypermethylated DMRs were strongly associated with genes encoding transcriptional regulators. Furthermore, subtelomeric regions and satellite repeats were hypomethylated in the NSCLC samples. We also identified DMRs that were specific to two of the major subtypes of NSCLC, adenocarcinomas and squamous cell carcinomas. Conclusions Collectively, we provide a resource containing genome-wide DNA methylation maps of NSCLC and their paired lung tissues, and comprehensive lists of known and novel DMRs and associated genes in NSCLC. PMID:22726460

  3. Carcinoma of the lung in the absence of asbestosis: The value of lung fiber burden analysis.

    PubMed

    Roggli, Victor L; Sporn, Thomas A

    2016-01-01

    Asbestos is universally recognized as a carcinogen for the lower respiratory tract. However, asbestos is a contributory factor in a small fraction of lung cancers, the vast majority of which are related to cigarette smoking. The challenge for the pathologist is to determine when a lung cancer may be attributed to past asbestos exposure. The finding of asbestosis either clinically or pathologically is a useful marker for such a determination. However, in the absence of asbestosis, it has been suggested that a fiber burden as determined by analytical electron microscopy within the range of asbestosis is sufficient for determination of a causal contribution. We report here an example of a case of lung cancer in which fiber burden studies showed an asbestos concentration within the range of asbestosis as determined by scanning electron microscopy (SEM). PMID:27043967

  4. Value of perioperative brachytherapy in the management of non-oat cell carcinoma of the lung

    SciTech Connect

    Hilaris, B.S.; Nori, D.; Beattie, E.J. Jr.; Martini, N.

    1983-08-01

    Nearly one-half of all patients with non-oat cell carcinoma of the lung are found to have mediastinal lymph node metastases at the time of initial presentation. There is no consensus today on what constitutes best treatment in patients whose disease is confined to the chest and in whom mediastinal lymph node metastases are the only evident site of tumor spread. The overall survival of these patients is so low that the majority have been either excluded from therapy or have been treated palliatively by external radiation therapy. In an attempt to improve the control of mediastinal lymph node metastases in the operable patients, a pilot study was begun in 1977 at Memorial Hospital to determine the value of perioperative brachytherapy (permanent Iodine-125 implantation of primary lung and a temporary Iridium-192 implantation of the mediastinum) with or without resection followed by a moderate dose of postoperative external beam irradiation. This pilot study has demonstrated that the combination of surgery, perioperative brachytherapy and external beam irradiation in non-oat cell carcinoma of the lung, metastatic to mediastinal lymph nodes, can improve the locoregional control and prolong survival with minimal early or late morbidity.

  5. Isodeoxyelephantopin from Elephantopus scaber (Didancao) induces cell cycle arrest and caspase-3-mediated apoptosis in breast carcinoma T47D cells and lung carcinoma A549 cells

    PubMed Central

    2014-01-01

    Background Isodeoxyelephantopin (IDOE) isolated from Elephantopus scaber L. (Didancao) is used in Chinese medicine for the treatment of some types of cancer. The anti-cancer mechanism of IDOE remains unclear. This study aims to investigate the antiproliferative activity of IDOE on breast carcinoma T47D cells and lung carcinoma A549 cells. Methods The growth inhibitory effects of IDOE on breast carcinoma T47D cells, lung carcinoma A549 cells, and normal lymphocytes were evaluated by the MTT assay. Morphological analysis of apoptosis induction was performed by acridine orange/ethidium bromide dual-staining and Hoechst 33342 nuclear staining. The cell cycle profile, caspase-3 expression, and annexin V staining were evaluated by flow cytometry. Results IDOE inhibited the growth of A549 and T47D cells in a dose- and time-dependent manner with IC50 values of 10.46 and 1.3 μg/mL, respectively. IDOE was not significantly toxic to normal lymphocytes. The cells became detached from the monolayer and rounded up, had fragmented nuclei and condensed chromatin, and the numbers of apoptotic cells increased (P = 0.0003). IDOE-induced cell death was associated with activated caspase-3 expression followed by cell cycle arrest at G2/M phase. Conclusions IDOE inhibited the proliferation of breast cancer cells and lung carcinoma cells and induced caspase-3-mediated apoptosis and cell cycle arrest in the treated cells. PMID:24742378

  6. Distinguishing Lung Adenocarcinoma from Lung Squamous Cell Carcinoma by Two Hypomethylated and Three Hypermethylated Genes: A Meta-Analysis.

    PubMed

    Huang, Tao; Li, Jinyun; Zhang, Cheng; Hong, Qingxiao; Jiang, Danjie; Ye, Meng; Duan, Shiwei

    2016-01-01

    Significant differences in the aberrant methylation of genes exist among various histological types of non-small cell lung cancer (NSCLC), which includes adenocarcinoma (AC) and squamous cell carcinoma (SCC). Different chemotherapeutic regimens should be administered to the two NSCLC subtypes due to their unique genetic and epigenetic profiles. The purpose of this meta-analysis was to generate a list of differentially methylated genes between AC and SCC. Our meta-analysis encompassed 151 studies on 108 genes among 12946 AC and 10243 SCC patients. Our results showed two hypomethylated genes (CDKN2A and MGMT) and three hypermethylated genes (CDH13, RUNX3 and APC) in ACs compared with SCCs. In addition, our results showed that the pooled specificity and sensitivity values of CDH13 and APC were higher than those of CDKN2A, MGMT and RUNX3. Our findings might provide an alternative method to distinguish between the two NSCLC subtypes. PMID:26862903

  7. Wedge resection and segmentectomy in patients with stage I non-small cell lung carcinoma.

    PubMed

    Reveliotis, Konstantinos; Kalavrouziotis, George; Skevis, Konstantinos; Charpidou, Andriani; Trigidou, Rodoula; Syrigos, Kostas

    2014-09-23

    The use of sublobar resections as definitive management in stage I non-small cell lung carcinoma is a controversial topic in the medical community. We intend to report the latest developments and trends in relative indications for each of the above-mentioned surgical approaches for the treatment of stage I non-small cell lung carcinoma as well as the results of studies regarding local recurrence, disease-free survival and five-year survival rates. We reviewed 45 prospective and retrospective studies conducted over the last 25 years listed in the Pubmed and Scopus electronic databases. Trials were identified through bibliographies and a manual search in journals. Authors, citations, objectives and results were extracted. No meta-analysis was performed. Validation of results was discussed. Segmentectomies are superior to wedge resections in terms of local recurrences and cancer-related mortality rates. Sublobar resections are superior to lobectomy in preserving the pulmonary parenchyma. High-risk patients should undergo segmentectomy, whereas lobectomies are superior to segmentectomies only for tumors >2 cm (T2bN0M0) in terms of disease-free and overall 5-year survival. In most studies no significant differences were found in tumors <2 cm. Disease-free surgical margins are crucial to prevent local recurrences. Systematic lymphadenectomy is mandatory regardless of the type of resection used. In sublobar resections with less thorough nodal dissections, adjuvant radiotherapy can be used. This approach is preferable in case of prior resection. In pure bronchoalveolar carcinoma, segmentectomy is recommended. Sublobar resections are associated with a shorter hospital stay. The selection of the type of resection in T1aN0M0 tumors should depend on characteristic of the patient and the tumor. Patient age, cardiopulmonary reserve and tumor size are the most important factors to be considered. However further prospective randomized trials are needed to investigate the efficacy

  8. Differential ethnic standards for lung functions, or one standard for all?

    PubMed

    Myers, J E

    1984-05-12

    The multiple regression equation predicting lung function values for a study population of South African Blacks is compared with equations predicting normal values for Blacks elsewhere, and in almost all cases is found to predict higher values. This is so despite the study population's high prevalence of respiratory disease and long history of exposure to crocidolite asbestos dust. This anomalous finding is explored in terms of some problems with studies generating normal values. In particular, the confounding effect of social class status on ethnic determinants of lung function is considered. Low 'normal' values for Blacks reported from South Africa and elsewhere are examined. The disadvantages to workers of being evaluated in relation to low norms are discussed in terms of preventive medicine and workmen's compensation. The application of a universal standard for all is proposed. PMID:6372134

  9. Selection of Patients With Non-Small-Cell Lung Carcinoma for Surgical Resection

    PubMed Central

    Rizk, Norman W.

    1985-01-01

    Cancer of the lung is rapidly increasing in incidence in both sexes and soon will overtake breast cancer as the most deadly cancer in women. Selection of patients with non-small-cell carcinoma for surgical resection is largely based on preoperative clinical staging, using the American Joint Committee on Cancer's TNM-based group staging protocol. Determining the presence or absence of mediastinal nodal metastasis is paramount and is currently best achieved by computed tomographic scanning of the chest and biopsy of enlarged nodes via mediastinoscopy. Certain types of stage III lesions, previously excluded from surgical treatment, are now recognized as operable. PMID:3909642

  10. Efficacy of an AC sinusoidal electric field for apoptosis induction in lung carcinoma cells (A549)

    NASA Astrophysics Data System (ADS)

    Park, Hyoun-Hyang; Lee, Seung S.; Hoon Lee, Dae

    2012-08-01

    An AC sinusoidal electric field was applied to lung carcinoma cells for the induction of apoptosis. The occurrence of apoptosis was determined by analysis of Annexin V/PI and DNA fragmentation. Additional evidence of apoptosis was confirmed by caspase-3 cleavage and disruption of mitochondrial membrane potential. These results demonstrated that the expression of apoptosis can be controlled by varying the magnitude and the duration of the field, and that the application of an AC electric field can stimulate the apoptosis via mitochondria-mediated pathway.

  11. Genetic Testing in Screening Patients With Stage IB-IIIA Non-Small Cell Lung Cancer That Has Been or Will Be Removed by Surgery (The ALCHEMIST Screening Trial)

    ClinicalTrials.gov

    2016-08-30

    Large Cell Lung Carcinoma; Lung Adenocarcinoma; Stage IB Non-Small Cell Lung Carcinoma; Stage IB Squamous Cell Lung Carcinoma; Stage IIA Non-Small Cell Lung Carcinoma; Stage IIA Squamous Cell Lung Carcinoma; Stage IIB Non-Small Cell Lung Carcinoma; Stage IIB Squamous Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIA Squamous Cell Lung Carcinoma

  12. [Subacute sensory neuronopathy associated with squamous cell carcinoma of the lung: a case report].

    PubMed

    Noto, Yuichi; Shiga, Kensuke; Fujinami, Jun; Mizuno, Toshiki; Nakagawa, Masanori; Tanaka, Keiko

    2009-08-01

    We report a 59-year-old man who developed dysesthesia in all extremities with severe loss of deep sensation over three months. A radiating radicular pain was also noted in the extremities. The nerve conduction study barely elicited sensory nerve action potentials both in the median and in the sural nerve. An extensive search for anti-neuronal antibodies including anti-Hu and anti-CV2 antibody was negetive. The biopsy specimen of an enlarged tracheobronchial lymph node revealed squamous cell carcinoma. The subsequent chemotherapy and radiation therapy for the neoplasm improved the radicular pain and the deep sensation to a moderate extent, leading to the diagnosis of paraneoplastic subacute sensory neuropathy (SSN). In general, cases with paraneoplastic SSN are associated mostly with small cell lung cancer, and quite rarely with squamous cell lung cancer. The early detection and the treatment of the primary tumor are crucial in a patient with subacute progression of sensory-dominant neuropathy. PMID:19827601

  13. Histological type of lung carcinoma in asbestos cement workers and matched controls.

    PubMed Central

    Johansson, L; Albin, M; Jakobsson, K; Mikoczy, Z

    1992-01-01

    Histological types of lung carcinoma were examined in a case series of workers exposed to asbestos cement dust (n = 29) and matched controls (n = 87). The proportion of adenocarcinomas was 31% among the exposed subjects and 15% among the controls (mid-p = 0.05). Among workers with high exposure the proportion of adenocarcinoma was even higher (45%, 5/11; mid-p = 0.03). The proportion of peripheral tumours tended to be higher among exposed cases than controls (24 v 12%, mid-p = 0.12). Lobe of origin did not differ, however, between exposed cases and controls. Thus the study indicates an association between the degree of exposure to asbestos and adenocarcinoma of the lung, and a peripheral rather than central localisation of the tumours, but with virtually the same distribution of lobe of origin as in the general population. PMID:1390268

  14. Histological type of lung carcinoma in asbestos cement workers and matched controls.

    PubMed

    Johansson, L; Albin, M; Jakobsson, K; Mikoczy, Z

    1992-09-01

    Histological types of lung carcinoma were examined in a case series of workers exposed to asbestos cement dust (n = 29) and matched controls (n = 87). The proportion of adenocarcinomas was 31% among the exposed subjects and 15% among the controls (mid-p = 0.05). Among workers with high exposure the proportion of adenocarcinoma was even higher (45%, 5/11; mid-p = 0.03). The proportion of peripheral tumours tended to be higher among exposed cases than controls (24 v 12%, mid-p = 0.12). Lobe of origin did not differ, however, between exposed cases and controls. Thus the study indicates an association between the degree of exposure to asbestos and adenocarcinoma of the lung, and a peripheral rather than central localisation of the tumours, but with virtually the same distribution of lobe of origin as in the general population. PMID:1390268

  15. Activated cholinergic signaling provides a target in squamous cell lung carcinoma.

    PubMed

    Song, Pingfang; Sekhon, Harmanjatinder S; Fu, Xiao Wen; Maier, Michelle; Jia, Yibing; Duan, Jie; Proskosil, Becky J; Gravett, Courtney; Lindstrom, Jon; Mark, Gregory P; Saha, Saurabh; Spindel, Eliot R

    2008-06-15

    The binding of exogenous nicotine to nicotinic acetylcholine (ACh) receptors (nAChR) and the binding of endogenous ACh to both nAChR and muscarinic ACh receptors (mAChR) stimulate growth of both small cell and non-small cell lung carcinomas. Understanding how cholinergic signaling is up-regulated in lung cancer may suggest new therapeutic approaches. Analysis of 28 squamous cell lung carcinomas (SCC) showed increased levels of alpha5 and beta3 nAChR mRNA and increased levels of ACh associated with increased levels of choline acetyltransferase mRNA and decreased cholinesterase mRNAs. Lynx1, an allosteric inhibitor of nAChR activity, was also decreased in SCC. Thus, cholinergic signaling is broadly increased in SCC caused by increased levels of receptors, increased levels of ligands, and decreased levels of receptor inhibitors. Partially explaining the cholinergic up-regulation seen in SCC, incubation of the H520 SCC cell line with nicotine increased levels of ACh secretion, increased expression of nAChR, and, as measured by electrophysiologic recording, increased activity of the expressed nAChR. Consistent with these effects, nicotine stimulated proliferation of H520 cells. One approach to blocking proliferative effects of nicotine and ACh on growth of lung cancers may be through M3 mAChR antagonists, which can limit the activation of mitogen-activated protein kinase that is caused by both nicotinic and muscarinic signaling. This was tested with the M3-selective muscarinic antagonist darifenacin. Darifenacin blocked nicotine-stimulated H520 growth in vitro and also blocked H520 growth in nude mice in vivo. Thus, cholinergic signaling is broadly up-regulated in SCC and blocking cholinergic signaling can limit basal and nicotine-stimulated growth of SCC. PMID:18559515

  16. Oral Rigosertib for Squamous Cell Carcinoma

    ClinicalTrials.gov

    2016-05-18

    Head and Neck Squamous Cell Carcinoma; Anal Squamous Cell Carcinoma; Lung Squamous Cell Carcinoma; Cervical Squamous Cell Carcinoma; Esophageal Squamous Cell Carcinoma; Skin Squamous Cell Carcinoma; Penile Squamous Cell Carcinoma

  17. CAFET Algorithm Reveals Wnt/PCP Signature in Lung Squamous Cell Carcinoma

    PubMed Central

    Hu, Yue; Galkin, Anna V.; Wu, Chunlei; Reddy, Venkateshwar; Su, Andrew I.

    2011-01-01

    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. PMID:22016777

  18. Role of pleural lavage cytology before resection for primary lung carcinoma.

    PubMed Central

    Okada, M; Tsubota, N; Yoshimura, M; Miyamoto, Y; Maniwa, Y

    1999-01-01

    OBJECTIVE: To investigate the role of pleural lavage cytology (PLC) in resection for primary lung carcinoma. SUMMARY BACKGROUND DATA: The prognostic significance of PLC before manipulation is still controversial. METHODS: Cytology of pleural lavage immediately after thoracotomy but before any manipulation of the lung was examined in 500 consecutive patients with lung cancer with no pleural effusion who underwent pulmonary resections. Eighteen patients who already had pleural dissemination were excluded from this study. RESULTS: Eighteen of 482 patients (3.7%) had positive cytologic findings. The positivity of PLC was significantly correlated with histology, extension of tumor to pleura, and presence of lymphatic permeation or vascular involvement by tumor. Positive lavage findings were seen only in adenocarcinoma. Because 6.3% of the patients with adenocarcinoma had positive cytologic findings, it is vital to perform PLC before curative resections for lung cancer, especially adenocarcinoma. The 5-year survival rates of the patients having negative and positive lavage findings were 52.9% and 14.6%, respectively. The prognosis of the patients with positive lavage findings was as poor as that of the patients with stage IIIB disease and that of the patients with malignant effusion. CONCLUSIONS: Positive findings on PLC indicate exfoliation of cancer cells into the pleural cavity, which is an essential prognostic factor. In addition, we should regard positive cytologic findings as a subclinical malignant pleural effusion that is pathologic stage T4. PMID:10203093

  19. Knockdown of S100A7 reduces lung squamous cell carcinoma cell growth in vitro and in vivo

    PubMed Central

    Liu, Guijuan; Wu, Qiang; Liu, Guilan; Song, Xueying; Zhang, Jihong

    2014-01-01

    Objective: S100A7 plays a role in the malignant potential of several epithelial cancers, and could candidate diagnostic marker or therapeutic target. Nuclear factor kappa B (NF-κB) regulates cancer cell growth and is modulated by phospholipase activity in many cancer cells. In the present study, we first evaluate the involvement of S100A7 in lung squamous cell carcinoma and its clinical usefulness for diagnosis. We then study whether knockdown of S100A7 in lung squamous cell carcinoma cells would reduce cell proliferation and NF-κB activity in vitro and attenuate tumor growth in vivo. Methods: We examined S100A7 expression in lung squamous cell carcinoma tissues by immunohistology .The human lung squamous cell carcinoma cell line NCI-H520 were transduced with short hairpin RNA targeting S100A7. Quantitative reverse transcriptase-polymerase chain reaction and immunoblotting confirmed knockdown of S100A7 messenger RNA and protein, respectively. Cell proliferation was evaluated by the MTT assay. NF-κB phosphorylation was assayed by western blot. 1×106 of NCI-H520/S100A7 knockdown cells were injected into the left flanks of nude mice (aged 6 to 8 weeks). Tumors were followed for 35 days, then removed and stained with hematoxylin and eosin, stained with Ki-67, and analyzed for S100A7 protein expression. Results: S100A7 protein levels were significantly higher in carcinoma specimens than in nonneoplastic tissues. S100A7 might be a useful marker for diagnosis of lung squamous cell carcinoma. In vitro data showed that inhibition of S100A7 decreased proliferation of NCI-H520 cells. S100A7 knockdown reduced NF-κB phosphorylation and tumor growth in vivo and vivo. Explanted knockdown tumors maintained lower S100A7 levels compared with wild-type, confirmed by immunohistology. Ki-67 staining was more prominent throughout the wild-type tumors compared with knockdown tumors. Conclusions: Our present results suggest that S100A7 level is a promising tool for diagnosis of lung

  20. RET-rearranged non-small-cell lung carcinoma: a clinicopathological and molecular analysis

    PubMed Central

    Tsuta, K; Kohno, T; Yoshida, A; Shimada, Y; Asamura, H; Furuta, K; Kushima, R

    2014-01-01

    Background: To elucidate clinicopathological characteristics of non-small-cell lung carcinoma (NSCLC) cases carrying RET rearrangements causing oncogenic fusions to identify responders to therapy with RET tyrosine kinase inhibitors. Methods: We investigated 1874 patients with carcinomas, including 1620 adenocarcinomas (ADCs), 203 squamous cell carcinomas (SCCs), 8 large cell carcinomas, and 43 sarcomatoid carcinomas (SACs). Fluorescence in situ hybridisation (FISH) and/or reverse transcription–PCR (RT–PCR) were performed to detect RET gene rearrangement. Results: In all, 22 cases (1.2%) showed RET rearrangements; all cases were of ADC histology. Of the 22 patients, 19 possessed KIF5B–RET fusion genes, whereas 3 possessed CCDC6–RET fusion genes. The RET-rearranged tumours were significantly more common in younger patients (P=0.038) and tended to occur in patients with no history of smoking (P=0.051). In addition, RET rearrangements were not associated with gender, occupational history (particularly radioactive exposure), tumour size, lymph node status, tumour stage, or patient survival. The predominant growth pattern in RET-rearranged ADCs was lepidic in 6 cases, papillary in 9 cases, acinar in 2 cases, micropapillary in 1 case, and solid in 4 cases. Cells with cytoplasmic mucin production were at least focally present in 12 of the 22 (54.5%) RET-rearranged ADC cases. Among the 21 analysed RET-rearranged tumours, RET immunopositivity was observed in 15 cases (71.4%), and was significantly associated with RET rearrangement (P<0.001). Conclusions: The RET rearrangements were observed in 1.2% of NSCLCs. All cases of RET rearrangement were ADCs. The RET rearrangements were more likely to be observed in younger patients. Although cytoplasmic mucin production was at least focally present in 54.5% of RET-rearranged ADCs, specific histological features were not detected. PMID:24504365

  1. Eating ability predicts subsequent quality of life in Chinese patients with breast, liver, lung, or nasopharyngeal carcinoma: a longitudinal analysis.

    PubMed

    Wong, Wing S; Fielding, Richard

    2008-01-01

    Eating dysfunction is a well-recognized consequence of orophagic tract cancers, but also occurs with other cancers. There is a relative absence of data assessing the impact of eating function on QoL in cancer populations other than those with disease of the oro-phagic tract. We assessed longitudinal changes in eating function and quality of life (QoL), and examined whether eating function predicted QoL over time in a sample of Chinese patients with breast, lung, liver, and nasopharyngeal cancers. Overall, 1 079 patients with breast, liver, lung, or nasopharyngeal carcinoma were assessed during their first outpatient visit (baseline) and at two follow-up interviews (FU1 and FU2). Three dimensions of eating function, including ability, appetite, and enjoyment, were assessed using three 11-point self-rated items. QoL was measured by the Chinese version of the Functional Assessment of Cancer Therapy-General Scale (FACT-G (Ch)). Linear mixed effects (LME) models evaluated mean differences on eating function and QoL scores across interviews and across cancer groups, and the effects of eating function on QoL. After adjustment for socio-demographic and medical variables, pain and depression, eating function significantly predicted patient overall (standardized betas ranged from 0.091 to 0.163, ps < 0.05), physical (standardized betas ranged from 0.101 to 0.200, ps < 0.05), and functional (standardized betas ranged from 0.120 to 0.162, ps < 0.05) aspects of QoL scores over time. Eating dysfunction significantly impacts QoL in cancer populations other than those with orophagic disease. Change of eating function appears to be a common problem in cancer patients regardless of cancer site. PMID:18097779

  2. Differential diagnosis of lung carcinoma with three-dimensional quantitative molecular vibrational imaging

    NASA Astrophysics Data System (ADS)

    Gao, Liang; Hammoudi, Ahmad A.; Li, Fuhai; Thrall, Michael J.; Cagle, Philip T.; Chen, Yuanxin; Yang, Jian; Xia, Xiaofeng; Fan, Yubo; Massoud, Yehia; Wang, Zhiyong; Wong, Stephen T. C.

    2012-06-01

    The advent of molecularly targeted therapies requires effective identification of the various cell types of non-small cell lung carcinomas (NSCLC). Currently, cell type diagnosis is performed using small biopsies or cytology specimens that are often insufficient for molecular testing after morphologic analysis. Thus, the ability to rapidly recognize different cancer cell types, with minimal tissue consumption, would accelerate diagnosis and preserve tissue samples for subsequent molecular testing in targeted therapy. We report a label-free molecular vibrational imaging framework enabling three-dimensional (3-D) image acquisition and quantitative analysis of cellular structures for identification of NSCLC cell types. This diagnostic imaging system employs superpixel-based 3-D nuclear segmentation for extracting such disease-related features as nuclear shape, volume, and cell-cell distance. These features are used to characterize cancer cell types using machine learning. Using fresh unstained tissue samples derived from cell lines grown in a mouse model, the platform showed greater than 97% accuracy for diagnosis of NSCLC cell types within a few minutes. As an adjunct to subsequent histology tests, our novel system would allow fast delineation of cancer cell types with minimum tissue consumption, potentially facilitating on-the-spot diagnosis, while preserving specimens for additional tests. Furthermore, 3-D measurements of cellular structure permit evaluation closer to the native state of cells, creating an alternative to traditional 2-D histology specimen evaluation, potentially increasing accuracy in diagnosing cell type of lung carcinomas.

  3. Cytogenetic damage in lymphocytes of patients undergoing therapy for small cell lung cancer and ovarian carcinoma

    SciTech Connect

    Padjas, Anna; Lesisz, Dominika; Lankoff, Anna; Banasik, Anna; Lisowska, Halina; Bakalarz, Robert; Gozdz, Stanislaw; Wojcik, Andrzej . E-mail: awojcik@pu.kielce.pl

    2005-12-01

    The level of cytogenetic damage in peripheral blood lymphocytes of patients undergoing chemotherapy has been analyzed incisively 20 years ago. The results showed that the highest level of cytogenetic damage was observed at the end of therapy. In recent years, the doses of anticancer drugs were intensified thanks to the discovery of colony stimulating factors. Therefore, it was interesting to analyze the kinetics of micronuclei formation in lymphocytes of patients undergoing modern chemotherapy. The frequencies of micronuclei were measured in lymphocytes of 6 patients with small cell lung cancer treated with a combination of cisplatin and etoposide and 7 patients with ovarian carcinoma treated with a combination of taxol and cisplatin. 3 patients with lung cancer received radiotherapy in addition to chemotherapy. Micronuclei were analyzed in lymphocytes collected before the start of therapy and 1 day before each following cycle of chemotherapy. The micronucleus frequencies were compared with the kinetics of leukocyte counts. The micronucleus frequencies showed an interindividual variability. On average, the frequencies of micronuclei increased during the first half of therapy and declined thereafter, reaching, in some patients with ovarian carcinoma, values below the pre-treatment level. Leukocyte counts decreased strongly at the beginning of therapy with an upward trend at the end. We suggest that the decline of micronuclei was due to repopulation of lymphocytes and acquired drug resistance.

  4. Ileal Intussusception Due to Metastasis from Squamous Cell Carcinoma of the Lung Resected 12 Years Previously.

    PubMed

    Nakamura, Tomoki; Chino, Osamu; Tajima, Takayuki; Tanaka, Yoichi; Yokoyama, Daiki; Hanashi, Tomoko; Sadahiro, Sotaro; Makuuchi, Hiroyasu

    2015-12-01

    An 88-year-old woman, with a history of resection of stage IIA lung cancer in 1998, was referred to our hospital in August 2010 complaining of upper abdominal pain, vomiting, and dark brown stools. After endoscopic examination, she was admitted with a diagnosis of Mallory-Weiss syndrome. Vomiting occurred when food intake was resumed after fasting. Intestinal obstruction was suspected on abdominal radiography, and complete small bowel obstruction was confirmed by contrast-enhanced imaging after placement of an ileus tube. A small intestinal tumor with intussusception was detected by computed tomography. At laparotomy, there was no ascites. Intussusception was found due to an ileal tumor located approximately 50 cm from the ileocecal valve, and we performed partial small bowel resection. The resected small intestine contained a submucosal tumor approximately 40 mm in diameter that had penetrated the bowel wall to reach the serosa. Pathological examination revealed a submucosal tumor that showed poor continuity with the surrounding mucosa, while the histology was squamous cell carcinoma. Immunohistochemistry showed that the tumor was CK7 positive, CK20 negative, TTF-1 negative, and CK10 positive. Based on these findings, we made a diagnosis of small intestinal metastasis at 12 years after radical resection of squamous cell carcinoma of the lung. PMID:26662663

  5. Surfactant protein B gene variations enhance susceptibility to squamous cell carcinoma of the lung in German patients

    PubMed Central

    Seifart, C; Seifart, U; Plagens, A; Wolf, M; von Wichert, P

    2002-01-01

    Genetic factors are thought to influence the risk for lung cancer. Since pulmonary surfactant mediates the response to inhaled carcinogenic substances, candidate genes may be among those coding for pulmonary surfactant proteins. In the present matched case–control study a polymorphism within intron 4 of the gene coding for surfactant specific protein B was analysed in 357 individuals. They were divided into 117 patients with lung cancer (40 patients with small cell lung cancer, 77 patients with non small cell lung cancer), matched controls and 123 healthy individuals. Surfactant protein B gene variants were analysed using specific PCR and cloned surfactant protein B sequences as controls. The frequency of the intron 4 variation was similar in both control groups (13.0% and 9.4%), whereas it was increased in the small cell lung cancer group (17.5%) and the non small cell lung cancer group (16.9%). The gene variation was found significantly more frequently in patients with squamous cell carcinoma (25.0%, P=0.016, odds ratio=3.2, 95%CI=1.24–8.28) than in the controls. These results indicate an association of the surfactant protein B intron 4 variants and/or its flanking loci with mechanisms that may enhance lung cancer susceptibility, especially to squamous cell carcinoma of the lung. British Journal of Cancer (2002) 37, 212–217. doi:10.1038/sj.bjc.6600353 www.bjcancer.com © 2002 Cancer Research UK PMID:12107845

  6. Surgical pathology of early stage non-small cell lung carcinoma

    PubMed Central

    Beasley, Mary Beth; Dembitzer, Francine R.

    2016-01-01

    The histologic classification of non-small cell lung carcinoma (NSCLC), particularly adenocarcinoma (ADC), has undergone extensive study in recent decades, ultimately resulting in an extensively updated classification system. The 2015 World Health Organization (WHO) classification of ADC provides greatly improved prognostic information in comparison to the 2004 WHO classification. Several issues still require further investigation: lepidic predominant ADC, prognostic significance of poor prognostic subtypes such as micropapillary carcinoma, the more recently described concept of spread of tumor through airspaces (STAS), and the utility of sublobar resections. While limited resection appears to be suitable for tumors with a ground glass radiographic appearance, which typically correspond to adenocarcinoma in situ (MIS) or minimally invasive adenocarcinoma (MIA) histologically, the role of sublobar resection in radiographic solid tumors is not as clear, and the impact of histologic subtypes with a poor prognosis needs further evaluation. Squamous cell carcinoma (SCC) has not been as extensively studied and the current classification lacks subclassification with significant prognostic information. PMID:27429964

  7. Accelerated cellular senescence phenotype of GAPDH-depleted human lung carcinoma cells

    SciTech Connect

    Phadke, Manali; Krynetskaia, Natalia; Mishra, Anurag; Krynetskiy, Evgeny

    2011-07-29

    Highlights: {yields} We examined the effect of glyceraldehyde 3-phosphate (GAPDH) depletion on proliferation of human carcinoma A549 cells. {yields} GAPDH depletion induces accelerated senescence in tumor cells via AMPK network, in the absence of DNA damage. {yields} Metabolic and genetic rescue experiments indicate that GAPDH has regulatory functions linking energy metabolism and cell cycle. {yields} Induction of senescence in LKB1-deficient lung cancer cells via GAPDH depletion suggests a novel strategy to control tumor cell proliferation. -- Abstract: Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is a pivotal glycolytic enzyme, and a signaling molecule which acts at the interface between stress factors and the cellular apoptotic machinery. Earlier, we found that knockdown of GAPDH in human carcinoma cell lines resulted in cell proliferation arrest and chemoresistance to S phase-specific cytotoxic agents. To elucidate the mechanism by which GAPDH depletion arrests cell proliferation, we examined the effect of GAPDH knockdown on human carcinoma cells A549. Our results show that GAPDH-depleted cells establish senescence phenotype, as revealed by proliferation arrest, changes in morphology, SA-{beta}-galactosidase staining, and more than 2-fold up-regulation of senescence-associated genes DEC1 and GLB1. Accelerated senescence following GAPDH depletion results from compromised glycolysis and energy crisis leading to the sustained AMPK activation via phosphorylation of {alpha} subunit at Thr172. Our findings demonstrate that GAPDH depletion switches human tumor cells to senescent phenotype via AMPK network, in the absence of DNA damage. Rescue experiments using metabolic and genetic models confirmed that GAPDH has important regulatory functions linking the energy metabolism and the cell cycle networks. Induction of senescence in LKB1-deficient non-small cell lung cancer cells via GAPDH depletion suggests a novel strategy to control tumor cell proliferation.

  8. FBI1/Akirin2 promotes tumorigenicity and metastasis of Lewis lung carcinoma cells.

    PubMed

    Komiya, Yuko; Akiyama, Hirotada; Sakumoto, Ryuji; Tashiro, Fumio

    2014-02-14

    The 14-3-3 family of proteins regulates various signaling pathways involved in cell cycle, apoptosis, stress response, and malignant transformation. We previously demonstrated that the β isoform of the 14-3-3 protein promotes cell growth and tumorigenicity of rat K2 hepatocellular carcinoma cells. We identified fourteen-three-three beta interactant 1 (FBI1)/Akirin2 as a binding partner of 14-3-3β and showed that the complex of these proteins promotes tumorigenicity and metastasis of K2 cells. In addition, we demonstrated that FBI1/Akirin2 downregulation shortened the duration of MAPK activity. Because 14-3-3β and FBI1/Akirin2 overexpression is observed in various cancer cell lines, 14-3-3β-FBI1/Akirin2 oncogenic function should be elucidated in different types of cancer. In this study, we used LLC1 Lewis lung carcinoma cells as a model. We established FBI1/Akirin2 knockdown cell clones through transfection of an antisense FBI1/Akirin2 expression vector and assessed the capacity for cell growth in vitro and tumorigenicity and metastasis in vivo. FBI1/Akirin2 downregulation decreased anchorage-independent growth, whereas the growth rate in monolayer culture was not affected. Moreover, an in vivo assay in nude mice showed that FBI1/Akirin2 overexpression is required for LLC1 tumor growth and metastasis. These results suggest that FBI1/Akirin2 plays an important role in oncogenesis of LLC1 lung carcinoma cells, and this protein may also serve as an oncogene in other cancers. PMID:24468084

  9. Differential DNA sequence deletions from chromosomes 3, 11, 13, and 17 in squamous-cell carcinoma, large-cell carcinoma, and adenocarcinoma of the human lung

    SciTech Connect

    Weston, A.; Willey, J.C.; Modali, R.; Sugimura, H.; McDowell, E.M.; Resau, J.; Light, B.; Haugen, A.; Mann, D.L.; Trump, B.F.; Harris, C.C. )

    1989-07-01

    Activation of protooncogens and inactivation of putative tumor suppressor genes are genetic lesions considered to be important in lung carcinogenesis. Fifty-four cases of non-small-cell lung cancer (23 adenocarcinomas, 23 squamous-cell carcinomas, and 8 large-cell carcinomas) were examined for loss of DNA sequences at 13 polymorphic genetic loci. Loss of heterozygosity was seen more frequently in squamous-cell carcinoma than in adenocarcinoma. The loss of DNA sequences from the short arm of chromosome 17 (D17S1 locus) was detected in 8 of 9 heterozygous cases of squamous-cell carcinoma and in only 2 of 11 heterozygous cases of adenocarcinomas. Loss of DNA sequences from chromosome 3 was seen in 16 of 31 cases where the constitutive DNA was heterozygous-i.e., informative. Loss of heterozygosity at the chromosome 13q locus, D13S3, was seen in 9 of 21 informative cases, and in 2 cases, both adenocarcinomas, duplication of the intact DNA sequences suggested the possibility that mitotic recombination had occurred. Frequent DNA sequence deletions, including those from chromosome 17, in squamous-cell carcinomas may reflect the extensive mutagenic and clastogenic effects of tobacco smoke that may lead to inactivation of putative tumor-suppressor genes.

  10. Molecular profiling of premalignant lesions in lung squamous cell carcinomas identifies mechanisms involved in stepwise carcinogenesis.

    PubMed

    Ooi, Aik T; Gower, Adam C; Zhang, Kelvin X; Vick, Jessica L; Hong, Longsheng; Nagao, Brian; Wallace, W Dean; Elashoff, David A; Walser, Tonya C; Dubinett, Steven M; Pellegrini, Matteo; Lenburg, Marc E; Spira, Avrum; Gomperts, Brigitte N

    2014-05-01

    Lung squamous cell carcinoma (SCC) is thought to arise from premalignant lesions in the airway epithelium; therefore, studying these lesions is critical for understanding lung carcinogenesis. Previous microarray and sequencing studies designed to discover early biomarkers and therapeutic targets for lung SCC had limited success identifying key driver events in lung carcinogenesis, mostly due to the cellular heterogeneity of patient samples examined and the interindividual variability associated with difficult to obtain airway premalignant lesions and appropriate normal control samples within the same patient. We performed RNA sequencing on laser-microdissected representative cell populations along the SCC pathologic continuum of patient-matched normal basal cells, premalignant lesions, and tumor cells. We discovered transcriptomic changes and identified genomic pathways altered with initiation and progression of SCC within individual patients. We used immunofluorescent staining to confirm gene expression changes in premalignant lesions and tumor cells, including increased expression of SLC2A1, CEACAM5, and PTBP3 at the protein level and increased activation of MYC via nuclear translocation. Cytoband enrichment analysis revealed coordinated loss and gain of expression in chromosome 3p and 3q regions, respectively, during carcinogenesis. This is the first gene expression profiling study of airway premalignant lesions with patient-matched SCC tumor samples. Our results provide much needed information about the biology of premalignant lesions and the molecular changes that occur during stepwise carcinogenesis of SCC, and it highlights a novel approach for identifying some of the earliest molecular changes associated with initiation and progression of lung carcinogenesis within individual patients. PMID:24618292

  11. Molecular profiling of premalignant lesions in lung squamous cell carcinomas identifies mechanisms involved in stepwise carcinogenesis

    PubMed Central

    Ooi, Aik T.; Gower, Adam C.; Zhang, Kelvin X.; Vick, Jessica L.; Hong, Longsheng; Nagao, Brian; Wallace, W. Dean; Elashoff, David A.; Walser, Tonya C.; Dubinett, Steven M.; Pellegrini, Matteo; Lenburg, Marc E.; Spira, Avrum; Gomperts, Brigitte N.

    2014-01-01

    Lung squamous cell carcinoma (SCC) is thought to arise from premalignant lesions in the airway epithelium; therefore studying these lesions is critical for understanding lung carcinogenesis. Previous microarray and sequencing studies designed to discover early biomarkers and therapeutic targets for lung SCC had limited success identifying key driver events in lung carcinogenesis, mostly due to the cellular heterogeneity of patient samples examined and the inter-individual variability associated with difficult to obtain airway premalignant lesions and appropriate normal control samples within the same patient. We performed RNA sequencing on laser-microdissected representative cell populations along the SCC pathological continuum of patient-matched normal basal cells, premalignant lesions, and tumor cells. We discovered transcriptomic changes and identified genomic pathways altered with initiation and progression of SCC within individual patients. We used immunofluorescent staining to confirm gene expression changes in premalignant lesions and tumor cells, including increased expression of SLC2A1, CEACAM5, and PTBP3 at the protein level and increased activation of MYC via nuclear translocation. Cytoband enrichment analysis revealed coordinated loss and gain of expression in chromosome 3p and 3q regions, respectively, during carcinogenesis. This is the first gene expression profiling study of airway premalignant lesions with patient-matched SCC tumor samples. Our results provide much needed information about the biology of premalignant lesions and the molecular changes that occur during stepwise carcinogenesis of SCC, and it highlights a novel approach for identifying some of the earliest molecular changes associated with initiation and progression of lung carcinogenesis within individual patients. PMID:24618292

  12. [Update of human tumor clonogenic assay in carcinoma of the lung].

    PubMed

    Kanzawa, F

    1985-08-01

    The human tumor clonogenic assay (HTCA) is a double-layer agar technique, which provides an in vitro prediction of the response of an individual patient's tumor to an antitumor agent. This paper briefly provides an outline of HTCA and its potential use in chemotherapy on patients with lung cancer. In our experience with culturing 123 carcinomas of the lung, 105 specimens (85%) could be subject to more than 5 chemosensitivity tests each by modifying the preparation method of single cell suspension in this system. Growth rate was improved in all types of primary human lung cancer with reasonable consistency. Further, metastatic tumors were capable of being successfully grown in a high percentage of cases, which was comparable to the results obtained for other kinds of tumors. There was no correlation of growth or cloning efficiency with histology, source, or previous chemotherapy. Using 50% or more inhibition on to colony formation as the criterion for chemosensitivity, response rates to vindesine or mitomycin C were 19% or 16%, respectively. The in vitro response rates of these or almost all other antitumor drugs seemed to be comparable to the clinical responses reported by various investigators. Correlation between in vitro chemosensitivity in HTCA and clinical response has been evaluated by various investigators, and the pooled data have demonstrated a good association between in vitro drug sensitivity and clinical response or lack of response. In lung cancer, HTCA had a 57% true positive rate and an 85% true negative rate for the prediction of drug sensitivity and resistance, respectively, of cancer patients to specific chemotherapeutic drugs. Although the system still has to undergo modification to resolve a number of theoretical and practical problems, it has potential uses in lung cancer chemotherapy. PMID:2992395

  13. Dietary diindolylmethane suppresses inflammation-driven lung squamous cell carcinoma in mice

    PubMed Central

    Song, Jung Min; Qian, Xuemin; Teferi, Fitsum; Pan, Jing; Wang, Yian; Kassie, Fekadu

    2014-01-01

    Inflammatory conditions of the lung such as chronic obstructive pulmonary disease (COPD) are known to increase lung cancer risk, particularly lung squamous cell carcinoma (LSCC). In the present study, we developed a mouse model of inflammation-driven LSCC that was induced by N-nitroso-trischloroethylurea (NTCU) and enhanced by lipopolysaccharide (LPS), a potent proinflammatory agent contained in tobacco and tobacco smoke, and determined the chemopreventive effects of BioResponse diindolylmethane (DIM) in the same model. Compared to mice treated with NTCU alone, mice treated with the combination of NTCU and LPS had a 9-fold increase in the number of bronchioles with LSCC. Also, compared to mice treated with LPS alone, mice treated with NTCU plus LPS showed significantly increased expression of the inflammatory cytokines IL-1α, IL-6, and TNFα (all three increased about 7-fold). Parallel to the increased cytokine gene expression, the NTCU plus LPS-treated group exhibited significantly enhanced activation of NF-κB, STAT3, ERK, p-38, and Akt, expression of p53, COX-2, and Mcl-1, and NF-κB- and STAT3-DNA binding in the lung. Dietary administration of DIM (10 µmol/g diet or 2460 ppm) to mice treated with NTCU plus LPS reduced the incidence of LSCC by 2-fold, suppressed activation/expression of proinflammatory and procarcinogenic proteins and NF-κB- and STAT3-DNA binding, but not the expression of cytokines and p53. This study highlights the potential significance of our mouse model to identify promising drugs or dietary agents for the chemoprevention of human LSCC and that DIM is a very good candidate for clinical lung cancer chemoprevention trials. PMID:25403850

  14. ECTOPIC ACTH SECRETION WITH CONCOMITANT HYPERAMYLASEMIA IN A PATIENT WITH SMALL CELL LUNG CARCINOMA: CASE REPORT.

    PubMed

    Cekerevac, Ivan; Petrović, Marina; Novković, Ljiljana; Bubanja, Dragana; Bubanja, Ivan; Djokić, Bojan; Stanković, Vesna; Jurisić, Vladimir

    2015-12-01

    Histologically confirmed small cell lung cancer associated with Cushing's syndrome and elevated amylase is rarely described in the literature. We present a case of a 63-year-old patient admitted to cardiology department due to shortness of breath, exhaustion, palpitations and nausea. Elevated values of troponin and electrocardiography suggested that he could have acute coronary syndrome. According to the radiologist's opinion, plane lung radiography was normal. Elevated level of amylase was found in both serum (3802 U/L, normal range 28-100) and urine (12012 U/L, normal range 0-450 U/L), as well as elevated sodium (156 mmol/L, normal range 137-147 mmol/L), hyperglycemia (12 mmol/L, normal range 3.8-6.1 mmol/L) and lowered serum potassium (1.7 mmol/L, normal range 3.5-5.3 mmol/L). Computerized tomography (CT) of the abdomen revealed a tumor of the left adrenal gland and enlargement of the right adrenal gland with normal structure of the pancreas. During hospitalization, the patient had blood while coughing and CT scan of the lungs showed a tumor 48x38x51 mm in size localized in the laterobasal segment of the left lung with mediastinal lymphadenopathy. He also had bilateral pleural effusions with signs of pulmonary embolism, which explained elevated troponin values. Biopsy confirmed microcellular lung carcinoma and tumor cells were diffusely positive for TTF-1 and focally for CK7, expressing markers of neuroendocrine differentiation (chromogranin +++, synaptophysin +++, NSE ++). Since neuroendocrine tumor was confirmed and the patient had low potassium and high glucose, hypercortisolism was suspected. High morning cortisol (1784 mmol/L, normal range 171-536) and unsuppressed ACTH (214 pg/L, < 60), as well as a high level of chromogranin (1339 µg/L, < 65) were determined. During hospital stay, the patient developed heart and respiratory failure and died in the second week of hospitalization. PMID:27017732

  15. ADAM23 is downregulated in side population and suppresses lung metastasis of lung carcinoma cells.

    PubMed

    Ota, Masahide; Mochizuki, Satsuki; Shimoda, Masayuki; Abe, Hitoshi; Miyamae, Yuka; Ishii, Ken; Kimura, Hiroshi; Okada, Yasunori

    2016-04-01

    Cancer cells contain a small population of cancer stem cells or cancer initiating cells, which can be enriched in the side population (SP) after fluorescence activated cell sorting. To examine the members of the ADAM, ADAMTS and MMP gene families related to phenotypes of the SP and the main population (MP), we screened the expression of all the members in the propagated SP and MP of A549 lung adenocarcinoma cells, and found that the relative expression ratio of ADAM23 in the MP to the SP is most highly increased, but none of them are increased in the SP. A similar result on the ADAM23 expression was obtained with another cell line, Calu-3 cells. Overexpression of ADAM23 inhibited colony formation, cell adhesion and migration, and knockdown of ADAM23 by shRNA showed the reverse effects. ADAM23-mediated suppression of colony formation, cell adhesion and migration was greatly reduced by treatment with neutralizing anti-ADAM23 antibody, anti-αvβ3 integrin antibody and/or ADAM23 disintegrin peptide. Expression of cancer stem cell-related genes, including AKRC1/2, TM4SF1 and NR0B1, was increased by knockdown of ADAM23. In addition, lung metastasis of A549 transfectants with different levels of ADAM23 expression was negatively regulated by the ADAM23 expression levels. Our data provide evidence that ADAM23 plays a role in suppression of cancer cell progression through interaction with αvβ3 integrin, and suggest that downregulation of ADAM23 in SP cells may contribute toward providing a cancer stem cell phenotype by facilitating the activity of integrin αvβ3. PMID:26800504

  16. Small cell neuroendocrine carcinomas of the lung do not harbor high-risk human papillomavirus.

    PubMed

    Hartley, Christopher P; Steinmetz, Heather B; Memoli, Vincent A; Tafe, Laura J

    2015-04-01

    High-risk subtypes of the human papillomavirus (HPV) are known to drive the pathogenesis of cervical, anogenital, and oropharyngeal squamous cell carcinomas. Recent reports have shown that HPV is also associated with small cell neuroendocrine carcinomas of the cervix and oropharynx. Little is known about HPV as a driver of neuroendocrine tumors at other sites, in particular, small cell lung cancer (SCLC). The aim of this study was to evaluate SCLC for the presence of high-risk HPV to further elucidate the role of HPV in SCLC. Archived formalin-fixed, paraffin-embedded surgical resection specimens from 20 primary SCLC from 19 patients were identified from 2004 to 2013. Two cervical small cell carcinomas were included as controls. Small cell neuroendocrine phenotype was confirmed by review of morphology and prior immunohistochemistry staining. Immunohistochemistry for p16 (INK4a) expression was performed in all cases. DNA was extracted from formalin-fixed, paraffin-embedded specimens and run on the Roche Linear Array HPV Genotyping test and a real-time polymerase chain reaction HPV assay. Pathologic tumor stage was collected from surgical pathology reports. High-risk HPV genotypes were not detected in any of the 20 SCLC specimens, whereas p16 was up-regulated in 14 (70%) of 20. p16 up-regulation can be used as an indicator of disruption of the Rb pathway either by integration of the HPV E7 oncoprotein or other mechanisms. In conclusion, our findings indicate that, unlike some other small cell neuroendocrine carcinomas, the pathogenesis of SCLC does not appear to be associated with high-risk HPV infection, a potentially very useful characteristic when determining primary from metastatic tumors. PMID:25661244

  17. The Use of P63 Immunohistochemistry for the Identification of Squamous Cell Carcinoma of the Lung

    PubMed Central

    Conde, Esther; Angulo, Bárbara; Redondo, Pilar; Toldos, Oscar; García-García, Elena; Suárez-Gauthier, Ana; Rubio-Viqueira, Belén; Marrón, Carmen; García-Luján, Ricardo; Sánchez-Céspedes, Montse; López-Encuentra, Angel; Paz-Ares, Luis; López-Ríos, Fernando

    2010-01-01

    Introduction While some targeted agents should not be used in squamous cell carcinomas (SCCs), other agents might preferably target SCCs. In a previous microarray study, one of the top differentially expressed genes between adenocarcinomas (ACs) and SCCs is P63. It is a well-known marker of squamous differentiation, but surprisingly, its expression is not widely used for this purpose. Our goals in this study were (1) to further confirm our microarray data, (2) to analize the value of P63 immunohistochemistry (IHC) in reducing the number of large cell carcinoma (LCC) diagnoses in surgical specimens, and (3) to investigate the potential of P63 IHC to minimize the proportion of “carcinoma NOS (not otherwise specified)” in a prospective series of small tumor samples. Methods With these goals in mind, we studied (1) a tissue-microarray comprising 33 ACs and 99 SCCs on which we performed P63 IHC, (2) a series of 20 surgically resected LCCs studied for P63 and TTF-1 IHC, and (3) a prospective cohort of 66 small thoracic samples, including 32 carcinoma NOS, that were further classified by the result of P63 and TTF-1 IHC. Results The results in the three independent cohorts were as follows: (1) P63 IHC was differentially expressed in SCCs when compared to ACs (p<0.0001); (2) half of the 20 (50%) LCCs were positive for P63 and were reclassified as SCCs; and (3) all P63 positive cases (34%) were diagnosed as SCCs. Conclusions P63 IHC is useful for the identification of lung SCCs. PMID:20808915

  18. Enhanced expression of Aggrus (T1alpha/podoplanin), a platelet-aggregation-inducing factor in lung squamous cell carcinoma.

    PubMed

    Kato, Yukinari; Kaneko, Mika; Sata, Makoto; Fujita, Naoya; Tsuruo, Takashi; Osawa, Motoki

    2005-01-01

    Aggrus (T1alpha/podoplanin, known as a specific marker for type I alveolar cells or lymphatic endothelial cells) is a transmembrane sialoglycoprotein that aggregates platelets. Previously, we showed that upregulated expression of Aggrus occurs in colorectal tumors or testicular tumors and could be associated with platelet-aggregating activity and metastatic ability. In testicular tumors, Aggrus is specifically expressed in seminoma. The present study investigates Aggrus expression in human primary lung cancer tissues of different types. Microarray analysis demonstrated that aggrus was significantly expressed in squamous cell carcinoma (10/15; 66.7%). Immunohistochemical analysis also showed that the incidence of positive staining in sections of squamous cell carcinoma (7/8; 87.5%) was higher than that in adenocarcinoma (2/13; 15.4%). Furthermore, Aggrus expression was detected in a squamous cell carcinoma cell line, NCI-H226, by real-time PCR. These findings indicated that overexpression of Aggrus occurred in squamous cell carcinoma of the lung. Therefore, Aggrus could be a useful diagnostic marker for squamous cell carcinoma of the lung. PMID:16006773

  19. ANG Promotes Proliferation and Invasion of the Cell of Lung Squamous Carcinoma by Directly Up-Regulating HMGA2

    PubMed Central

    Xu, Li; Liao, Wei-Lin; Lu, Qi-Jue; Li, Chun-Guang; Yuan, Yang; Xu, Zhi-Yun; Huang, Sheng-Dong; Chen, He-Zhong

    2016-01-01

    Objective: To determine the mechanism of Angiogenin(ANG) function involved in the carcinogenesis of lung squamous cell carcinoma. Methods: 12 patients' normal tissue and cancerous tissue were collected. ANG expression in the squamous cell carcinoma of the lung was evaluated by qRT-PCR and western-blot. The regulation of ANG on proliferation, migration, invasion, and apoptosis of SK-MES-1 cells were analyzed by Cell Counting Kit-8, Transwell migration chamber, Transwell invasion chamber, and Annexin V-FITC assay, respectively. PCR array was utilized for screening potential target genes of ANG. Chromatin immunoprecipitation(ChIP) assays and luciferase assay were adopted for investigation of ANG's direct regulation on HMGA2. Results: ANG expression is increased in the squamous cell carcinoma of the lung tissue. In vitro experiments results indicated that overexpression of ANG promotes proliferation and invasion capability of SK-MES-1 cells. The candidate proliferation, migration, and invasion related ANG target gene found was HMGA2, expression levels of which were also enhanced in lung squamous cell carcinoma tissue. The direct regulation of ANG on HMGA2 was verified by ChIP and luciferase assay results. Furthermore, down-regulating HMGA2 significantly alleviated the suppression effects of ANG on proliferation, migration, and invasion of SK-MES-1 cells. Conclusions: Our data illustrated the mechanisms that ANG promoted the cell of SQCLC proliferation, migration, and invasion capacity via directly up-regulating HMGA2. PMID:27162546

  20. Dietary energy restriction reduces high-fat diet-enhanced metastasis of Lewis lung carcinoma in mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Obesity is a risk factor for cancer. The objective of this study was to determine the effects of dietary energy restriction on high-fat diet-enhanced spontaneous metastasis of Lewis lung carcinoma (LLC) in mice. Male C57BL/6 mice were fed an AIN93G diet or a high-fat diet (16% or 45% of energy fro...

  1. Monocyte chemotactic protein-1 deficiency reduces spontaneous metastasis of Lewis lung carcinoma in mice fed a high-fat diet

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Obesity is a risk factor for cancer. Adipose tissue produces pro-inflammatory adipokines that contribute obesity-related malignant progression. This study investigated the effects of monocyte chemotactic protein-1 (MCP-1) deficiency on pulmonary metastasis of Lewis lung carcinoma (LLC) in male C57...

  2. Dietary supplementation with methylseleninic acid, but not selenomethionine, reduces spontaneous metastasis of Lewis lung carcinoma in mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The present study investigated the effects of dietary supplementation with methylseleninic acid (MSeA), in comparison with selenomethionine (SeMet), on spontaneous metastasis of Lewis lung carcinoma (LLC) in male C57BL/6 mice using intramuscular and subcutaneous injection models. Mice were fed AIN9...

  3. [Photodynamic therapy in combined treatment of stage III non-small cell lung carcinoma].

    PubMed

    Akopov, A L; Rusanov, A A; Molodtsova, V P; Chistiakov, I V; Kazakov, N V; Urtenova, M A; Rait, Makhmud; Papaian, G V

    2013-01-01

    The aim of the study was to evaluate the effectiveness of combined treatment of locally advanced lung cancer with the use of neoadjuvant chemotherapy and surgery with the use of pre- and intraoperative photodynamic therapy. 20 patients with IIIa (n=7) and IIIb (n=13) stage of non-small cell lung carcinoma were included. At the time of diagnosis the surgical treatment was decided to abstain because of the trachea invasion in 9 patients, wide mediastinal invasion in 2 patients and contralateral mediastinal lymph nodes metastases in 2 patients; pneumonectomy was not possible due to the poor respiratory function in 7 patients. Neoadjuvant therapy included 3 courses of chemotherapy and endobronchial photodynamic therapy. During the operation, along with the lung resection (pneumonectomy - 15, lobectomy - 5), photodynamic therapy of the resection margins were carried out. No adjuvant treatment was done. Preoperative treatment led to partial regress of the disease in all cases; the goal of surgery was the complete tumor removal. No complications of the photodynamic therapy were observed. 18 surgical interventions were radical and two non-complete microscopically (R1). Postoperative morbidity was 20%, one patient died due to massive gastrointestinal bleeding. The average follow-up period was 18 months: 19 patients were alive, of them 18 with no signs of the disease recurrence. The first experience of the combined use of neoadjuvant chemotherapy and surgery with pre- and intraoperative photodynamic therapy demonstrates safety and efficacy of the suggested treatment tactics. PMID:23612332

  4. Effects of dimethyltriazenes on in vitro Lewis lung carcinoma tumor lines with different metastatic capacity.

    PubMed

    Zupi, G; Corsi, A; Sacchi, A; Lassiani, L; Giraldi, T

    1984-01-01

    The effects of a selective antimetastatic agent: the aryldimethyltriazene derivative 1-p-(3,3-dimethyl-1-triazeno)benzoic acid potassium salt (DM-COOK) have been examined on two in vitro tumor cell lines derived from lung metastases of Lewis lung carcinoma. These stabilized in vitro tumor cell lines named C108 and BC215 have been reported to differ in their metastatic potential evaluated as lung colony forming ability and as the number of spontaneous metastases produced after intramuscular implant of tumor cells. The cytotoxic effect of DM-COOK in vitro was also compared with the one demonstrated by the structure-related compound 4-(3,3-dimethyl-1-triazeno)imidazole-5- carboxamide (DTIC) on the same variant lines. Survival curves show a different chemosensitivity of the two in vitro lines to the DM-COOK treatment, whereas no differences were detected between C108 and BC215 after exposure to DTIC. Moreover, DM-COOK and DTIC exhibit different trends of cell killing, implying different mechanisms of action for the two drugs. Results are discussed in view of the selective in vitro action of the aryldimethyltriazene derivative DM-COOK on cells which express a high metastatic potential. PMID:6480290

  5. Magneto-reactance based detection of MnO nanoparticle-embedded Lewis lung carcinoma cells

    NASA Astrophysics Data System (ADS)

    Devkota, J.; Howell, M.; Mukherjee, P.; Srikanth, H.; Mohapatra, S.; Phan, M. H.

    2015-05-01

    We demonstrate the capacity of detecting magnetically weak manganese oxide (MnO) nanoparticles and the Lewis lung carcinoma (LLC) cancer cells that have taken up these nanoparticles using a novel biosensor based on the magneto-reactance (MX) effect of a soft ferromagnetic amorphous ribbon with a microhole-patterned surface. While the magnetic moment of the MnO nanoparticles is relatively small, and a magneto-impedance based sensor fails to detect them in solution (0.05 mg/ml manganese oxide lipid micellar nanoparticles) and inside cells at low concentrations (8.25 × 104 cells/ml), the detection of these nanoparticles and the LLC cells containing them is achieved with the MX-based sensor, which, respectively, reaches the detection sensitivity of ˜3.6% and 2.8% as compared to the blank cells. Since the MnO nanoparticles are a promising contrast agent for magnetic resonance imaging (MRI) of lung cells, the MX-based biosensing technique can be developed as a pre-detection method for MRI of lung cancer cells.

  6. Paracrine control of differentiation in the alveolar carcinoma, A549, by human foetal lung fibroblasts.

    PubMed Central

    Speirs, V.; Ray, K. P.; Freshney, R. I.

    1991-01-01

    Synthesis of pulmonary surfactant (PS) is necessary for normal functioning of the lungs and its production is indicative of normal differentiated lung. The human alveolar carcinoma, A549, has been found to synthesis and secrete PS in vitro. The purpose of this study was to optimise the culture conditions for PS synthesis by A549 as well as to determine the potential role of foetal lung fibroblasts in the induction of PS by glucocorticoids. A549 cells growing in filter wells produced higher levels of PS in response to steroid, a 5-fold increase on the filter well compared to only a 1.5-fold increase when the cells were cultured on a conventional plastic substrate. A549 cells grown in filter wells responded to coculture with fibroblasts whether in direct contact or separated co-culture. A 20-fold increase in PS over control values was observed in separated steroid-treated co-cultures, suggesting the presence of a diffusible factor. A partially purified factor was isolated from fibroblast conditioned medium which was capable of inducing differentiation and other phenotypic changes in A549, namely induction of PS, reduction of plasminogen activator activity and reduction in the in vivo growth of A549 xenografts in nude mice. These results suggest that, under the correct conditions, A549 cells, although transformed, still retain the capacity to respond to differentiation-inducing signals from normal fibroblasts. Images Figure 5 PMID:1654985

  7. Evaluation of androgen receptor and GATA binding protein 3 as immunohistochemical markers in the diagnosis of metastatic breast carcinoma to the lung.

    PubMed

    Hattori, Yukinori; Yoshida, Akihiko; Yoshida, Masayuki; Takahashi, Masahide; Tsuta, Koji

    2015-06-01

    Differentiating metastatic breast carcinoma in the lungs from primary lung tumors and mesotheliomas is important for determining prognosis and treatment. We evaluated novel breast specific markers, androgen receptor (AR) and GATA binding protein 3 (GATA3) immunohistostaining, for this differential, and compare to other traditional markers. The specimens comprised 33 metastatic breast carcinomas to the lung, 566 primary lung tumors (170 adenocarcinomas, 157 squamous cell carcinomas, 31 pleomorphic carcinomas, 115 large cell neuroendocrine carcinomas, 43 small cell carcinomas, and 49 typical carcinoids) and 42 malignant mesotheliomas. They were analyzed by immunohistochemistry using antibodies to AR, GATA3, estrogen receptor (ER), progesterone receptor (PgR), mammaglobin, gross cystic disease fluid protein-15 (GCDFP-15). Of the metastatic breast carcinomas, immunohistostaining of AR, GATA3, ER, PgR, mammaglobin, GCDFP-15 were positive in 27 cases (81.8%), 24 cases (72.7%), 26 cases (78.8%), 13 cases (39.4%), 12 cases (36.4%), 9 cases (27.3%), respectively. Of primary lung tumors and mesotheliomas, staining of AR, GATA3, ER, PgR, mammaglobin, GCDFP-15 were positive in 18 cases (3%), 3 cases (0.5%), 4 cases (0.7%), 2 cases (0.3%), 0 case (0%), 2 cases (0.3%), respectively. Immunohistochemistry of AR and GATA3 are reliable for differentiating metastatic breast carcinoma from primary lung tumors and mesotheliomas. PMID:25727644

  8. Integrated 18F-Fluorodeoxyglucose–Positron Emission Tomography/Dynamic Contrast-Enhanced Computed Tomography to Phenotype Non–Small Cell Lung Carcinoma

    PubMed Central

    Shastry, Manu; Miles, Kenneth A.; Win, Thida; Janes, Sam M.; Endozo, Raymond; Meagher, Marie; Ell, Peter J.; Groves, Ashley M.

    2012-01-01

    We applied modern molecular and functional imaging to the pretreatment assessment of lung cancer using combined dynamic contrast-enhanced computed tomography (DCE-CT) and 18F-fluorodeoxyglucose–positron emission tomography (18F-FDG-PET) to phenotype tumors. Seventy-four lung cancer patients were prospectively recruited for 18F-FDG-PET/DCE-CT using PET/64-detector CT. After technical failures, there were 64 patients (35 males, 29 females; mean age [± SD] 67.5 ± 7.9 years). DCE-CT yielded tumor peak enhancement (PE) and standardized perfusion value (SPV). The uptake of 18F-FDG quantified on PET as the standardized uptake value (SUVmax) assessed tumor metabolism. The median values for SUVmax and SPV were used to define four vascular-metabolic phenotypes. There were associations (Spearman rank correlation [rs]) between tumor size and vascular-metabolic parameters: SUVmax versus size (rs = .40, p = .001) and SUV/PE versus size (r = .43, p < .001). Patients with earlier-stage (I–IIA, n = 30) disease had mean (± SD) SUV/PE 0.36 ± 0.28 versus 0.56 ± 0.32 in later-stage (stage IIB–IV, n = 34) disease (p = .007). The low metabolism with high vascularity phenotype was significantly more common among adenocarcinomas (p = .018), whereas the high metabolism with high vascularity phenotype was more common among squamous cell carcinomas (p = .024). Other non–small cell lung carcinoma tumor types demonstrated a high prevalence of the high metabolism with low vascularity phenotype (p = .028). We show that tumor subtypes have different vascular-metabolic associations, which can be helpful clinically in managing lung cancer patients to hone targeted therapy. PMID:22954179

  9. Integrated 18F-fluorodeoxyglucose-positron emission tomography/dynamic contrast-enhanced computed tomography to phenotype non-small cell lung carcinoma.

    PubMed

    Shastry, Manu; Miles, Kenneth A; Win, Thida; Janes, Sam M; Endozo, Raymond; Meagher, Marie; Ell, Peter J; Groves, Ashley M

    2012-01-01

    We applied modern molecular and functional imaging to the pretreatment assessment of lung cancer using combined dynamic contrast-enhanced computed tomography (DCE-CT) and (18)F-fluorodeoxyglucose-positron emission tomography ((18)F-FDG-PET) to phenotype tumors. Seventy-four lung cancer patients were prospectively recruited for (18)F-FDG-PET/DCE-CT using PET/64-detector CT. After technical failures, there were 64 patients (35 males, 29 females; mean age [± SD] 67.5 ± 7.9 years). DCE-CT yielded tumor peak enhancement (PE) and standardized perfusion value (SPV). The uptake of (18)F-FDG quantified on PET as the standardized uptake value (SUV(max)) assessed tumor metabolism. The median values for SUV(max) and SPV were used to define four vascular-metabolic phenotypes. There were associations (Spearman rank correlation [rs]) between tumor size and vascular-metabolic parameters: SUV(max) versus size (rs  =  .40, p  =  .001) and SUV/PE versus size (r  =  .43, p < .001). Patients with earlier-stage (I-IIA, n  =  30) disease had mean (± SD) SUV/PE 0.36 ± 0.28 versus 0.56 ± 0.32 in later-stage (stage IIB-IV, n  =  34) disease (p  =  .007). The low metabolism with high vascularity phenotype was significantly more common among adenocarcinomas (p  =  .018), whereas the high metabolism with high vascularity phenotype was more common among squamous cell carcinomas (p  =  .024). Other non-small cell lung carcinoma tumor types demonstrated a high prevalence of the high metabolism with low vascularity phenotype (p  =  .028). We show that tumor subtypes have different vascular-metabolic associations, which can be helpful clinically in managing lung cancer patients to hone targeted therapy. PMID:22954179

  10. Depletion of C3orf1/TIMMDC1 inhibits migration and proliferation in 95D lung carcinoma cells.

    PubMed

    Wu, Huiling; Wang, Wenbing; Xu, Huaxi

    2014-01-01

    In our previous study, we identified an association of high expression of c3orf1, also known as TIMMDC1 (translocase of inner mitochondrial membrane domain-containing protein 1), with metastatic characteristics in lung carcinoma cells. To investigate the preliminary function and mechanism of this mitochondrial protein, we depleted C3orf1 expression by introducing siRNA into 95D lung carcinoma cells. We demonstrated that C3orf1 depletion significantly suppressed 95D cell growth and migration. We confirmed C3orf1 localization in the inner mitochondrial membrane and showed that mitochondrial viability, membrane potential, and ATPase activity were remarkably reduced upon depletion of C3orf1. Microarray data indicated that genes involved in regulation of cell death, migration, and cell-cycle arrest were significantly altered after C3orf1 depletion for 48 h. The expression of genes involved in focal adhesion, ECM-receptor interaction, and p53-signaling pathways were notably altered. Furthermore, cell-cycle arrest genes such as CCNG2 and PTEN as well as genes involved in cell migration inhibition, such as TIMP3 and COL3A1, were upregulated after C3orf1 depletion in 95D cells. Concurrently, expression of the migration-promoting gene NUPR1 was markedly reduced, as confirmed by real-time PCR. We conclude that C3orf1 is critical for mitochondrial function, migration, and proliferation in 95D lung carcinoma cells. Depletion of C3orf1 inhibited cell migration and cell proliferation in association with upregulation of genes involved in cell-cycle arrest and cell migration inhibition. These results suggest that C3orf1 (TIMMDC1) may be a viable treatment target for lung carcinoma, and that further study of the role of this protein in lung carcinoma pathogenesis is justified. PMID:25391042

  11. Effect of DR4 promoter methylation on the TRAIL-induced apoptosis in lung squamous carcinoma cell.

    PubMed

    Wang, Wenwu; Qi, Xiaoyan; Wu, Minghua

    2015-10-01

    The aim of the present study was to examine the relationship between DR4 methylation status and gene expression and to determine whether DR4 methylation status affects TRAIL-induced apoptosis in lung squamous carcinoma cells. MSP, RT-PCR and western blot analysis were applied to detect the methylation status and gene expression. An MTT assay was used to detect the cell proliferation inhibition rate and flow cytometry was utilized to detect the apoptotic rate. The results showed that there was no association of the apoptotic rate with the clinicopathological characteristics for 80.6% of 36 lung squamous carcinoma patients in the methylation status (P>0.05). In the lung squamous carcinoma patients, the probability of DR4 low expression was approximately 58.3%, which may be associated with DR4 promoter methylation. The results also showed that a low expression of DR4 was correlated with the prognosis of patients. The in vitro experiments suggested DR4 genes of H226 and SK-MES-1 cells were in the methylation status and their mRNA and proteins had a low expression. Following intervention with 5-Aza-CdR, the DR4 genes of H226 and SK-MES-1 cells were in the unmethylation status and their mRNA and protein expression was significantly upregulated compared with the pre-interference ones, with differences being statistically significant (P<0.05). In addition, following interference with 5-Aza-CdR, H226 and SK-MES-1 cells became significantly sensitive to TRAIL (P<0.05). The results revealed 5-Aza‑CdR was able to reverse DR4 methy-lation status to upregulate its expression, thereby increasing the TRAIL-induced apoptosis in lung squamous carcinoma cells. Therefore, combining 5-Aza-CdR and TRAIL is a new strategy for treating lung squamous carcinoma. PMID:26238205

  12. miRNAs, a potential target in the treatment of Non-Small-Cell Lung Carcinomas.

    PubMed

    Malleter, Marine; Jacquot, Catherine; Rousseau, Bénédicte; Tomasoni, Christophe; Juge, Marcel; Pineau, Alain; Sakanian, Vehary; Roussakis, Christos

    2012-09-15

    Lung cancer is a serious public health problem and Non Small Cell Lung Carcinoma, NSCLC, is particularly resistant to current treatments. So it is important to find new strategies that are active against NSCLC. miRNA is implicated in cancer and may be implicated in NSCLC. Our team has been working on two genes HEF1, a gene implicated in different functions of cell cycle and B2, a large non-coding RNA (nc RNA). These two genes have the same localisation: chromosome 6 and locus p24-25. nc RNA B2 may be involved in the regulation of HEF1. Firstly, we examine a bank of different human miRNAs known to interact with exons of HEF1. HEF1 and B2 were overexpressed in vitro by treating NSCLC-N6 with the cytostatic molecule A190, and carried out qRT-PCR for the expression of miRNA. Secondly, using specific software, we sought for structures originating from the B2 RNA sequence which might interact with HEF1 and assessed their expression. This strategy enabled us to confirm firstly that known miRNAs that can interact with exons of HEF1 are expressed in NSCLC-N6 cells. More precisely this strategy highlighted overexpression of one miRNA, hsa-miR-146b, listed in miRbase. The second step of the studies highlighted the expression of miRNA, potentially sequences originating from B2 in the NSCLC-N6. This miRNA overexpressed might be one of the regulators of the gene HEF1 and consequently implies on the carcinogenesis of lung cancer. So in the future it could be a potential and an innovative way to find a new strategy for the treatment of lung cancer. PMID:22732573

  13. Integration of chemotherapy and radiation therapy for small cell carcinoma of the lung

    SciTech Connect

    Holoye, P.Y.; Libnoch, J.A.; Byhardt, R.W.; Cox, J.D.

    1982-09-01

    Two chemotherapy trials using cyclophosphamide, doxorubicine hydrochloride and high-dose vincristine sulfate with or without methotrexate have induced a 93% incidence of complete remission in limited disease presentation of small cell bronchogenic carcinoma of the lung and 39% incidence in extensive disease. The first without consolidation radiotherapy had a local failure rate of 65%, which dropped to 17% with consolidation radiotherapy to the primary and mediastinum. Prophylactic whole brain radiotherapy prevented local recurrence in 98% of evaluable patients. One carcinomatous meningitis and 5 intraspinal recurrences were noted among the 38 patients in the CAV-M trial. We conclude that high-dose vincristine sulfate is associated with an improved incidence of complete remission; that prophylactic whole brain radiotherapy has been highly successful; that prevention of intraspinal recurrence will necessitate the use of craniospinal axis radiation therapy and consolidation radiation therapy improves local control of primary and mediastinum.

  14. Genesis of squamous cell lung carcinoma. Sequential changes of proliferation, DNA ploidy, and p53 expression.

    PubMed Central

    Hirano, T.; Franzén, B.; Kato, H.; Ebihara, Y.; Auer, G.

    1994-01-01

    Squamous cell lung carcinomas (SCCs) represent a highly malignant group of tumors, and effective treatment is greatly dependent upon early diagnosis. However, objective diagnosis of atypia is difficult and useful markers need to be defined. In this study, genomic instability, cell proliferation, and cellular accumulation of mutant p53, as reflected by DNA aneuploidy, proliferating cell nuclear antigen, and p53 immunoreactivity, respectively, were evaluated in bronchial squamous metaplasia without atypia (n = 4), bronchial squamous metaplasia with low-grade atypia (n = 12), bronchial squamous metaplasia with high-grade atypia (n = 15), early-stage SCC (n = 15), and advanced-stage SCC (n = 33). Our results suggest that hyperproliferation is an early event followed by DNA aneuploidy, which in turn precedes p53 immunoreactivity in the genesis of SCC. We conclude that routine assessment of proliferating cell nuclear antigen, DNA ploidy, and p53 may be valuable for the early diagnosis of SCC. Images Figure 2 PMID:7906095

  15. Interactions of ozone and antineoplastic drugs on rat lung fibroblasts and Walker rat carcinoma cells

    SciTech Connect

    Wenzel, D.G.; Morgan, D.L.

    1983-05-01

    Cultured rat lung fibroblasts (F-cells) and Walker rat carcinoma cells (WRC-cells) labeled with /sup 51/Cr were exposed to the following antitumor drugs alone or with O/sub 3/: carmustine (BCNU), doxorubicin (Dox), cisplatin (CPt), mitomycin C (Mit C) or vitamin K/sub 3/ (Vit K). Release of /sup 51/Cr (cell injury) was greater for F-cells than WRC-cells with any single treatment. Pretreatment with any drug (400 microM), except for Vit K with WRC-cells, did not significantly increase O/sub 3/-induced loss of /sup 51/Cr. Co-exposure of F-cells to drugs and O/sub 3/ resulted in a marked potentiation of O/sub 3/-induced injury with Vit K, and an inhibition with Dox.

  16. Fructose-bisphosphate aldolase a is a potential metastasis-associated marker of lung squamous cell carcinoma and promotes lung cell tumorigenesis and migration.

    PubMed

    Du, Sha; Guan, Zhuzhu; Hao, Lihong; Song, Yang; Wang, Lan; Gong, Linlin; Liu, Lu; Qi, Xiaoyu; Hou, Zhaoyuan; Shao, Shujuan

    2014-01-01

    Fructose-bisphosphate aldolase A (ALDOA) is a key enzyme in glycolysis and is responsible for catalyzing the reversible conversion of fructose-1,6-bisphosphate to glyceraldehydes-3-phosphate and dihydroxyacetone phosphate. ALDOA contributes to various cellular functions such as muscle maintenance, regulation of cell shape and mobility, striated muscle contraction, actin filament organization and ATP biosynthetic process. Here, we reported that ALDOA is a highly expressed in lung squamous cell carcinoma (LSCC) and its expression level is correlated with LSCC metastasis, grades, differentiation status and poor prognosis. Depletion of ALDOA expression in the lung squamous carcinoma NCI-H520 cells reduces the capabilities of cell motility and tumorigenesis. These data suggest that ALDOA could be a potential marker for LSCC metastasis and a therapeutic target for drug development. PMID:24465716

  17. Fructose-Bisphosphate Aldolase A Is a Potential Metastasis-Associated Marker of Lung Squamous Cell Carcinoma and Promotes Lung Cell Tumorigenesis and Migration

    PubMed Central

    Hao, Lihong; Song, Yang; Wang, Lan; Gong, Linlin; Liu, Lu; Qi, Xiaoyu; Hou, Zhaoyuan; Shao, Shujuan

    2014-01-01

    Fructose-bisphosphate aldolase A (ALDOA) is a key enzyme in glycolysis and is responsible for catalyzing the reversible conversion of fructose-1,6-bisphosphate to glyceraldehydes-3-phosphate and dihydroxyacetone phosphate. ALDOA contributes to various cellular functions such as muscle maintenance, regulation of cell shape and mobility, striated muscle contraction, actin filament organization and ATP biosynthetic process. Here, we reported that ALDOA is a highly expressed in lung squamous cell carcinoma (LSCC) and its expression level is correlated with LSCC metastasis, grades, differentiation status and poor prognosis. Depletion of ALDOA expression in the lung squamous carcinoma NCI-H520 cells reduces the capabilities of cell motility and tumorigenesis. These data suggest that ALDOA could be a potential marker for LSCC metastasis and a therapeutic target for drug development. PMID:24465716

  18. Potential of the aminosterol, squalamine in combination therapy in the rat 13,762 mammary carcinoma and the murine Lewis lung carcinoma.

    PubMed

    Teicher, B A; Williams, J I; Takeuchi, H; Ara, G; Herbst, R S; Buxton, D

    1998-01-01

    Squalamine, a naturally-occurring aminosterol, has demonstrated antiangiogenic activity in several experimental models. Extended treatment with other antiangiogenic agents has been shown to increase tumor oxygenation. Tumor oxygenation was measured using an Eppendorf pO2 histograph polarographic pO2 electrode system in the rat 13,762 mammary carcinoma after treatment of the tumor-bearing animals with squalamine (40 mglkg) on days 4 through 18 post tumor implantation. Under air breathing conditions, the hypoxic fraction (percent of pO2 readings < 5 mmHg) was 53% in controls and was decreased to 38% in the squalamine treated animals. While squalamine administration alone produced only a modest effect on the growth of the 13,762 tumor, there were increases in tumor growth delay of 1.9- to 2.5-fold when squalamine was administered along with cyclophosphamide, cisplatin and paclitaxel compared with the tumor growth delays observed with the chemotherapeutic agents alone. To determine the efficacy of squalamine alone and along with cytotoxic therapies against a model of primary and systemic disease, squalamine was administered to animals bearing the Lewis lung carcinoma by daily subcutaneous injection or by continuous infusion on days 4 through 18 post tumor implantation. Squalamine as a single agent had only a modest effect on the growth of the primary Lewis lung tumor but increased the tumor growth delays produced by cyclophosphamide, cisplatin, paclitaxel and 5-fluorouracil by 2.4- to 3.8-fold compared with the anticancer drugs alone. Squalamine administration alone substantially decreased the number of lung metastases found in animals bearing the Lewis lung carcinoma and further decreased the number of lung metastases when administered along with the chemotherapeutic agents. PMID:9703911

  19. Carboplatin and Paclitaxel With or Without Bevacizumab and/or Cetuximab in Treating Patients With Stage IV or Recurrent Non-Small Cell Lung Cancer

    ClinicalTrials.gov

    2015-09-01

    Recurrent Large Cell Lung Carcinoma; Recurrent Lung Adenocarcinoma; Recurrent Squamous Cell Lung Carcinoma; Stage IV Large Cell Lung Carcinoma; Stage IV Lung Adenocarcinoma; Stage IV Squamous Cell Lung Carcinoma

  20. Thyroid-like follicular carcinoma of the kidney with metastases to the lungs and retroperitoneal lymph nodes.

    PubMed

    Dhillon, Jasreman; Tannir, Nizar M; Matin, Surena F; Tamboli, Pheroze; Czerniak, Bogdan A; Guo, Charles C

    2011-01-01

    Thyroid-like follicular carcinoma of the kidney is an extremely rare variant of renal cell carcinoma. Most previously reported cases presented as incidental small tumors confined to the kidney. Here we report a unique case in which the patient presented with flank pain and hematuria. Imaging studies demonstrated a large tumor in the right kidney and metastases to the lungs and retroperitoneal lymph nodes. Both the renal tumor and the sampled lung metastasis were composed almost entirely of follicles with dense, colloid-like material resembling thyroid follicular carcinoma. However, no lesion was found in the thyroid gland; and the patient's thyroid function test results were normal. The tumor cells were immunoreactive for PAX2 and PAX8 but lacked reactivity for thyroglobulin and thyroid transcription factor-1. To our knowledge, this is the first case of thyroid-like follicular carcinoma of the kidney to be initially associated with marked symptoms and widespread metastases, providing evidence that this rare variant of renal cell carcinoma can be clinically aggressive. PMID:20971497

  1. Thyroid-like follicular carcinoma of the kidney with metastases to the lungs and retroperitoneal lymph nodes

    PubMed Central

    Dhillon, Jasreman; Tannir, Nizar M.; Matin, Surena F.; Tamboli, Pheroze; Czerniak, Bogdan A.; Guo, Charles C.

    2014-01-01

    Summary Thyroid-like follicular carcinoma of the kidney is an extremely rare variant of renal cell carcinoma. Most previously reported cases presented as incidental small tumors confined to the kidney. Here we report a unique case in which the patient presented with flank pain and hematuria. Imaging studies demonstrated a large tumor in the right kidney and metastases to the lungs and retroperitoneal lymph nodes. Both the renal tumor and the sampled lung metastasis were composed almost entirely of follicles with dense, colloid-like material resembling thyroid follicular carcinoma. However, no lesion was found in the thyroid gland, and the patient’s thyroid function tests were normal. The tumor cells were immunoreactive for PAX2 and PAX8 but lacked reactivity for thyroglobulin and thyroid transcription factor-1. To our knowledge, this is the first case of thyroid-like follicular carcinoma of the kidney to be initially associated with marked symptoms and widespread metastases, providing evidence that this rare variant of renal cell carcinoma can be clinically aggressive. PMID:20971497

  2. Tissue spray ionization mass spectrometry for rapid recognition of human lung squamous cell carcinoma

    PubMed Central

    Wei, Yiping; Chen, Liru; Zhou, Wei; Chingin, Konstantin; Ouyang, Yongzhong; Zhu, Tenggao; Wen, Hua; Ding, Jianhua; Xu, Jianjun; Chen, Huanwen

    2015-01-01

    Tissue spray ionization mass spectrometry (TSI-MS) directly on small tissue samples has been shown to provide highly specific molecular information. In this study, we apply this method to the analysis of 38 pairs of human lung squamous cell carcinoma tissue (cancer) and adjacent normal lung tissue (normal). The main components of pulmonary surfactants, dipalmitoyl phosphatidylcholine (DPPC, m/z 757.47), phosphatidylcholine (POPC, m/z 782.52), oleoyl phosphatidylcholine (DOPC, m/z 808.49), and arachidonic acid stearoyl phosphatidylcholine (SAPC, m/z 832.43), were identified using high-resolution tandem mass spectrometry. Monte Carlo sampling partial least squares linear discriminant analysis (PLS-LDA) was used to distinguish full-mass-range mass spectra of cancer samples from the mass spectra of normal tissues. With 5 principal components and 30 – 40 Monte Carlo samplings, the accuracy of cancer identification in matched tissue samples reached 94.42%. Classification of a tissue sample required less than 1 min, which is much faster than the analysis of frozen sections. The rapid, in situ diagnosis with minimal sample consumption provided by TSI-MS is advantageous for surgeons. TSI-MS allows them to make more informed decisions during surgery. PMID:25961911

  3. Minnelide: A Novel Therapeutic That Promotes Apoptosis in Non-Small Cell Lung Carcinoma In Vivo

    PubMed Central

    Rousalova, Ilona; Banerjee, Sulagna; Sangwan, Veena; Evenson, Kristen; McCauley, Joel A.; Kratzke, Robert; Vickers, Selwyn M.; Saluja, Ashok; D’Cunha, Jonathan

    2013-01-01

    Background Minnelide, a pro-drug of triptolide, has recently emerged as a potent anticancer agent. The precise mechanisms of its cytotoxic effects remain unclear. Methods Cell viability was studied using CCK8 assay. Cell proliferation was measured real-time on cultured cells using Electric Cell Substrate Impedence Sensing (ECIS). Apoptosis was assayed by Caspase activity on cultured lung cancer cells and TUNEL staining on tissue sections. Expression of pro-survival and anti-apoptotic genes (HSP70, BIRC5, BIRC4, BIRC2, UACA, APAF-1) was estimated by qRTPCR. Effect of Minnelide on proliferative cells in the tissue was estimated by Ki-67 staining of animal tissue sections. Results In this study, we investigated in vitro and in vivo antitumor effects of triptolide/Minnelide in non-small cell lung carcinoma (NSCLC). Triptolide/Minnelide exhibited anti-proliferative effects and induced apoptosis in NSCLC cell lines and NSCLC mouse models. Triptolide/Minnelide significantly down-regulated the expression of pro-survival and anti-apoptotic genes (HSP70, BIRC5, BIRC4, BIRC2, UACA) and up-regulated pro-apoptotic APAF-1 gene, in part, via attenuating the NF-κB signaling activity. Conclusion In conclusion, our results provide supporting mechanistic evidence for Minnelide as a potential in NSCLC. PMID:24143232

  4. Keratin proteins in human lung carcinomas. Combined use of morphology, keratin immunocytochemistry, and keratin immunoprecipitation.

    PubMed Central

    Banks-Schlegel, S. P.; McDowell, E. M.; Wilson, T. S.; Trump, B. F.; Harris, C. C.

    1984-01-01

    Light-microscopic immunocytochemistry and electron microscopy demonstrated that adenocarcinomas (AC) and squamous cell (epidermoid) carcinomas (SCCs) of human lung contained keratin proteins in the form of tonofilament bundles. However, moderately differentiated (md) SCCs contained abundant keratin, whereas poorly differentiated (pd) SCCs and all ACs contained lesser amounts. Lung tumors with the diagnosis of AC or SCC, as defined by WHO criteria, were also analyzed by immunoprecipitation techniques for the presence of keratin proteins. Regardless of the degree of tumor differentiation, SCCs contained a 44 kd keratin which was lacking in ACs. Interestingly, normal bronchial epithelium also contained the same 44 kd keratin. In addition, as SCCs became more differentiated, they exhibited even greater differences in the profile of synthesized keratins. Specifically, the relative abundance of the intermediate-sized keratins (57 and 59 kd) was increased in the md SCCs. Although keratin protein patterns appear to be a valuable adjunct in distinguishing AC from SCC, their usefulness as a diagnostic tool will require survey of a larger number of poorly differentiated tumors. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:6198920

  5. Cardamonin Inhibits Metastasis of Lewis Lung Carcinoma Cells by Decreasing mTOR Activity

    PubMed Central

    Niu, Pei-Guang; Zhang, Yu-Xuan; Shi, Dao-Hua; Liu, Ying; Chen, Yao-Yao; Deng, Jie

    2015-01-01

    The mammalian target of rapamycin (mTOR) regulates the motility and invasion of cancer cells. Cardamonin is a chalcone that exhibits anti-tumor activity. The previous study had proved that the anti-tumor effect of cardamonin was associated with mTOR inhibition. In the present study, the anti-metastatic effect of cardamonin and its underlying molecule mechanisms were investigated on the highly metastatic Lewis lung carcinoma (LLC) cells. The proliferation, invasion and migration of LLC cells were measured by MTT, transwell and wound healing assays, respectively. The expression and activation of mTOR- and adhesion-related proteins were assessed by Western blotting. The in vivo effect of cardamonin on the metastasis of the LLC cells was investigated by a mouse model. Treated with cardamonin, the proliferation, invasion and migration of LLC cells were significantly inhibited. The expression of Snail was decreased by cardamonin, while that of E-cadherin was increased. In addition, cardamonin inhibited the activation of mTOR and its downstream target ribosomal S6 kinase 1 (S6K1). Furthermore, the tumor growth and its lung metastasis were inhibited by cardamonin in C57BL/6 mice. It indicated that cardamonin inhibited the invasion and metastasis of LLC cells through inhibiting mTOR. The metastasis inhibitory effect of cardamonin was correlated with down-regulation of Snail and up-regulation of E-cadherin. PMID:25996501

  6. Prognostic significance of CpG island methylator phenotype in surgically resected small cell lung carcinoma.

    PubMed

    Saito, Yuichi; Nagae, Genta; Motoi, Noriko; Miyauchi, Eisaku; Ninomiya, Hironori; Uehara, Hirofumi; Mun, Mingyon; Okumura, Sakae; Ohyanagi, Fumiyoshi; Nishio, Makoto; Satoh, Yukitoshi; Aburatani, Hiroyuki; Ishikawa, Yuichi

    2016-03-01

    Methylation is closely involved in the development of various carcinomas. However, few datasets are available for small cell lung cancer (SCLC) due to the scarcity of fresh tumor samples. The aim of the present study is to clarify relationships between clinicopathological features and results of the comprehensive genome-wide methylation profile of SCLC. We investigated the genome-wide DNA methylation status of 28 tumor and 13 normal lung tissues, and gene expression profiling of 25 SCLC tissues. Following unsupervised hierarchical clustering and non-negative matrix factorization, gene ontology analysis was performed. Clustering of SCLC led to the important identification of a CpG island methylator phenotype (CIMP) of the tumor, with a significantly poorer prognosis (P = 0.002). Multivariate analyses revealed that postoperative chemotherapy and non-CIMP were significantly good prognostic factors. Ontology analyses suggested that the extrinsic apoptosis pathway was suppressed, including TNFRSF1A, TNFRSF10A and TRADD in CIMP tumors. Here we revealed that CIMP was an important prognostic factor for resected SCLC. Delineation of this phenotype may also be useful for the development of novel apoptosis-related chemotherapeutic agents for treatment of the aggressive tumor. PMID:26748784

  7. The role of consolidation irradiation in combined modality therapy of small cell carcinoma of the lung

    SciTech Connect

    Byhardt, R.W.; Cox, J.D.; Holoye, P.Y.; Libnoch, J.A.

    1982-08-01

    Forty-four patients with small cell carcinoma of the lung (SCCL) were treated with a program of combined chemotherapy and radiation therapy. Prophylactic cranial irradiation was given concurrent with the first of six planned cycles of chemotherapy consisting of Cyclophosphamide, Adriamycin, Vincristine and high dose Methotrexate (CAV-M). All patients judged as complete responders (CR) received consolidative thoracic irradiation (CTI) to the locoregional primary lung involvement. The CR rate to chemotherapy alone was 84% for patients with limited disease (LD) and 44% for extensive disease. In comparison to a prior trial, which used similar chemotherapy, but with irradiation withheld until primary site relapse, the actuarial primary site relapse rate at 2 years was reduced by CTI from 92% to 18% (P < .01). The median primary site remission duration has not yet been reached in the CTI group and was 34 weeks without CTI (P < .01). CTI increased the 2 year actuarial survival from 6% to 66% (P < .01) in the chemotherapy CR patients.Median survival has not yet been reached in the CTI group, but was 48 weeks without CTI (P < .01). Leptomeningeal spinal cord relapse in patients with no prior central nervous system (CNS) involvement occurred in 16% of patients relapsing.

  8. Tissue spray ionization mass spectrometry for rapid recognition of human lung squamous cell carcinoma

    NASA Astrophysics Data System (ADS)

    Wei, Yiping; Chen, Liru; Zhou, Wei; Chingin, Konstantin; Ouyang, Yongzhong; Zhu, Tenggao; Wen, Hua; Ding, Jianhua; Xu, Jianjun; Chen, Huanwen

    2015-05-01

    Tissue spray ionization mass spectrometry (TSI-MS) directly on small tissue samples has been shown to provide highly specific molecular information. In this study, we apply this method to the analysis of 38 pairs of human lung squamous cell carcinoma tissue (cancer) and adjacent normal lung tissue (normal). The main components of pulmonary surfactants, dipalmitoyl phosphatidylcholine (DPPC, m/z 757.47), phosphatidylcholine (POPC, m/z 782.52), oleoyl phosphatidylcholine (DOPC, m/z 808.49), and arachidonic acid stearoyl phosphatidylcholine (SAPC, m/z 832.43), were identified using high-resolution tandem mass spectrometry. Monte Carlo sampling partial least squares linear discriminant analysis (PLS-LDA) was used to distinguish full-mass-range mass spectra of cancer samples from the mass spectra of normal tissues. With 5 principal components and 30 - 40 Monte Carlo samplings, the accuracy of cancer identification in matched tissue samples reached 94.42%. Classification of a tissue sample required less than 1 min, which is much faster than the analysis of frozen sections. The rapid, in situ diagnosis with minimal sample consumption provided by TSI-MS is advantageous for surgeons. TSI-MS allows them to make more informed decisions during surgery.

  9. CXCR6 expression in non-small cell lung carcinoma supports metastatic process via modulating metalloproteinases

    PubMed Central

    Mir, Hina; Singh, Rajesh; Kloecker, Goetz H.; Lillard, James W.; Singh, Shailesh

    2015-01-01

    Lung cancer (LuCa) is the leading cause of cancer-related deaths worldwide regardless of the gender. High mortality associated with LuCa is due to metastasis, molecular mechanisms of which are yet to be defined. Here, we present evidence that chemokine receptor CXCR6 and its only natural ligand, CXCL16, are significantly expressed by non-small cell lung cancer (NSCLC) and are involved in the pathobiology of LuCa. CXCR6 expression was significantly higher in two subtypes of NSCLC (adenocarcinomas-ACs and squamous cell carcinoma-SCCs) as compared to non-neoplastic tissue. Additionally, serum CXCL16 was significantly elevated in LuCa cases as compared to healthy controls. Similar to CXCR6 tissue expression, serum level of CXCL16 in AC patients was significantly higher than SCC patients. Biological significance of this axis was validated using SCC and AC cell lines. Expression of CXCR6 was higher in AC cells, which also showed higher migratory and invasive potential than SCC. Differences in migratory and invasive potential between AC and SCC were due to differential expression of metalloproteinases following CXCL16 stimulation. Hence, our findings suggest clinical and biological significance of CXCR6/CXCL16 axis in LuCa, which could be used as potential prognostic marker and therapeutic target. PMID:25888629

  10. Hypoglycemia, hypopotassemia and hyperleukocytosis associated with squamous cell carcinoma of the lung.

    PubMed

    Nakamura, H; Imamura, T; Kimura, N; Niho, Y; Okeda, T; Yanase, T

    1982-01-01

    We studied a patient with lung cancer, who exhibited severe systemic derangements of metabolism causing cachexia preceding the appearance of a large bulky tumor. The data described herein left no doubt that lung cancer growing in the patient acted as a powerful hypoglycemic factor, setting in motion widespread metabolic disorders. Inappropriate secretion of insulin may be involved in the manifestation of hypoglycemia. However, no ectopic secretion of insulin, glucagon, ACTH and aldosterone appeared to be associated with the carcinoma in the patient. From the present and previous observations, it is stressed that progressive energy loss from the patient occurs by virtue of a combination of severe anorexia and the establishment of a systemic energy-losing cycle dependent on an interplay of glycolysis in the cancer cells and stimulated gluconeogenesis in the host tissues, which in turn results in derangements of protein, lipid and electrolyte metabolism. Attempts to ameliorate the patient's distress and counterbalance the effect of the tumor by parenteral hyperalimentation were not satisfactory and resulted in only a temporary improvement. This study also demonstrated that marked granulocytosis was the result of production of an excess granulopoietic colony stimulating activity by the cancer cells. PMID:6978422

  11. Differential diagnosis of lung lesion in breast carcinoma: a metachronous neoplasm or metastasis?

    PubMed

    Maddala, Raja Naga Mahesh; Udupa, Karthik; Thomas, Joseph; Pai, Kanthilatha

    2016-01-01

    A 34-year-old woman-a diagnosed case of pT1N1MO, stage IIa, estrogen and progesterone receptor positive (ER, PR) positive, Her2 negative carcinoma of the left breast-was managed with modified radical mastectomy and adjuvant chemotherapy. While planning for radiotherapy, she was found to have a well-defined enhancing lesion with spiculated margins in the superior segment of the right lower lobe along with a heterogeneously enhancing right hilar lymph node on CT. Histopathological evaluation of the lesion was suggestive of adenocarcinoma. The lesion was negative for ER, PR receptors, mammoglobin and gross cystic disease fluid protein. Thyroid transcription factor 1 (TTF-1) was positive, suggesting a primary lung adenocarcinoma rather than metastatic lesion from the breast. This case clearly signifies the importance of histopathological diagnosis of suspicious metastatic lesions in the setting of early breast cancer. We would also like to highlight the importance of TTF-1 in differentiating primary lung malignancy from metastasis. PMID:27170610

  12. A rare case of primary peripheral epithelial myoepithelial carcinoma of lung

    PubMed Central

    Shen, Cheng; Wang, Xin; Che, Guowei

    2016-01-01

    Abstract Background: Primary salivary gland–type tumors of lung are rare. Epithelial–myoepithelial carcinoma (EMC) of the lung is a minor salivary gland–type tumor subtype. Methods: We report a very rare case of EMC located in the peripheral left lower lobe that was diagnosed in a 58-year-old man and this is the first study in which we summarize all the patients with primary peripheral lung EMC concerned with the clinical features. Informed consent was obtained from the patient. Results: Chest computed tomography displayed an anomalous soft tissue mass with slightly lobular borders in the peripheral segment of the left lower lobe and closed to the visceral pleura. The surgery was performed by using video-assisted thoracic surgery. Grossly, the tumor was solitary, well-circumscribed, and unencapsulated endobronchial lesion. A microscopic examination revealed that it was circumscribed, although the tumor borders may show single cells or clusters of cells proliferating away from the main tumor mass. The inner tubular layer showed epithelial cell characteristics, whereas the outer layer exhibited myoepithelial cell characteristics. Immunostaining for P40, P63, and cytokeratin 5/6 was positive. However, the anaplastic lymphoma kinase-V, thyroid transcription factor-1, synaptophysin, chromogranin A and napsin A were negative. Conclusions: Literature review showed that most of patients with peripheral EMC were asymptomatic. Computed tomography and magnetic resonance imaging scans are able to indicate the presence of peripheral EMC. Pathological analysis is an effective method to clarify the diagnosis. Surgery is a regular treatment method. To facilitate the preoperative diagnosis and avoid the misdiagnosis of such a rare disease, more cases will need to be reported. PMID:27583848

  13. Deuterium-depleted water inhibits human lung carcinoma cell growth by apoptosis

    PubMed Central

    CONG, FENG-SONG; ZHANG, YA-RU; SHENG, HONG-CAI; AO, ZONG-HUA; ZHANG, SU-YI; WANG, JU-YONG

    2010-01-01

    To investigate the in vivo and in vitro inhibitory effects of deuterium-depleted water (DDW) on human lung cancer and the possible mechanisms underlying these effects, we cultured and treated human lung carcinoma cell line A549 and human embryonic lung fibroblasts HLF-1 with various concentrations of DDW from 2 to 72 h. Cellular growth inhibition rates were determined using the 3-(4, 5-dimethyldiazol-2-yl)-2, 5-diphenyltetrazolium-bromide) (MTT) proliferation assay. A549 cells were treated with 50±5 ppm DDW, and the morphology and structure of cells were observed by scanning electron microscopy (SEM). We observed alterations in the cellular skeleton by transmission electron microscopy (TEM) and changes in cell cycle by flow cytometry. Our data showed that DDW significantly inhibited the proliferation of A549 cells at a specific time point, and cells demonstrated the characteristic morphological changes of apoptosis under SEM and TEM. The length of the S phase increased significantly in cells treated with 50 ppm DDW, whereas the G0 to G1 phase and G2 to M phase were decreased. We observed DDW-induced cellular apoptosis using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and DNA fragment analyses. In addition, we established a tumor transplantion model by injecting H460 tumor cells into subcutaneous tissue of BALB/c mice treated with DDW for 60 days. We determined the tumor inhibition rate of treated and control groups and found that the tumor weight was significantly decreased and the tumor inhibition rate was approximately 30% in the DDW group. We conclude that DDW is a promising new anticancer agent with potential for future clinical application. PMID:22993540

  14. Involvement of highly sulfated chondroitin sulfate in the metastasis of the Lewis lung carcinoma cells.

    PubMed

    Li, Fuchuan; Ten Dam, Gerdy B; Murugan, Sengottuvelan; Yamada, Shuhei; Hashiguchi, Taishi; Mizumoto, Shuji; Oguri, Kayoko; Okayama, Minoru; van Kuppevelt, Toin H; Sugahara, Kazuyuki

    2008-12-01

    The altered expression of cell surface chondroitin sulfate (CS) and dermatan sulfate (DS) in cancer cells has been demonstrated to play a key role in malignant transformation and tumor metastasis. However, the functional highly sulfated structures in CS/DS chains and their involvement in the process have not been well documented. In the present study, a structural analysis of CS/DS from two mouse Lewis lung carcinoma (3LL)-derived cell lines with different metastatic potentials revealed a higher proportion of Delta(4,5)HexUA-GalNAc(4,6-O-disulfate) generated from E-units (GlcUA-GalNAc(4, 6-O-disulfate)) in highly metastatic LM66-H11 cells than in low metastatic P29 cells, although much less CS/DS is expressed by LM66-H11 than P29 cells. This key finding prompted us to study the role of CS-E-like structures in experimental lung metastasis. The metastasis of LM66-H11 cells to lungs was effectively inhibited by enzymatic removal of tumor cell surface CS or by preadministration of CS-E rich in E-units in a dose-dependent manner. In addition, immunocytochemical analysis showed that LM66-H11 rather than P29 cells expressed more strongly the CS-E epitope, which was specifically recognized by the phage display antibody GD3G7. More importantly, this antibody and a CS-E decasaccharide fraction, the minimal structure recognized by GD3G7, strongly inhibited the metastasis of LM66-H11 cells probably by modifying the proliferative and invading behavior of the metastatic tumor cells. These results suggest that the E-unit-containing epitopes are involved in the metastatic process and a potential target for the diagnosis and treatment of malignant tumors. PMID:18930920

  15. KRAS Mutation in Small Cell Lung Carcinoma and Extrapulmonary Small Cell Cancer

    PubMed Central

    Kodaz, Hilmi; Taştekin, Ebru; Erdoğan, Bülent; Hacıbekiroğlu, İlhan; Tozkır, Hilmi; Gürkan, Hakan; Türkmen, Esma; Demirkan, Bora; Uzunoğlu, Sernaz; Çiçin, İrfan

    2016-01-01

    Background: Lung cancer is one of the most lethal cancers. It is mainly classified into 2 groups: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Extrapulmonary small cell carcinomas (EPSCC) are very rare. The Ras oncogene controls most of the cellular functions in the cell. Overall, 21.6% of human cancers contain a Kirsten Ras (KRAS) mutation. SCLC and EPSCC have several similar features but their clinical course is different. Aims: We investigated the KRAS mutation status in SCLC and EPSCC. Study design: Mutation research. Methods: Thirty-seven SCLC and 15 EPSCC patients were included in the study. The pathological diagnoses were confirmed by a second pathologist. KRAS analysis was performed in our medical genetic department. DNA isolation was performed with primary tumor tissue using the QIAamp DNA FFPE Tissue kit (Qiagen; Hilden, Germany) in all patients. The therascreen KRAS Pyro Kit 24 V1 (Qiagen; Hilden, Germany) was used for KRAS analyses. Results: Thirty-four (91.9%) of the SCLC patients were male, while 11 (73.3%) of the EPSCC l patients were female. SCLC was more common in males, and EPSCC in females (p=0.001). A KRAS mutation was found in 6 (16.2%) if SCLC patients. The most common mutation was Q61R (CAA>CGA). Among the 15 EPSCC patients, 2 had a KRAS mutation (13.3%). When KRAS mutant and wild type patients were compared in the SCLC group, no difference was found for overall survival (p=0.6). Conclusion: In previous studies, the incidence of KRAS mutation in SCLC was 1–3%; however, it was 16.2% in our study. Therefore, there may be ethnic and geographical differences in the KRAS mutations of SCLC. As a result, KRAS mutation should not be excluded in SCLC.

  16. [INTRAOPERATIVE DETECTION OF SENTINEL LYMPH NODES USING INFRARED IMAGING SYSTEM IN LOCAL NON-SMALL CELL CARCINOMA OF LUNG].

    PubMed

    Akopov, A L; Papayan, G V; Chistyakov, I V; Karlson, A; Gerasin, A V; Agishev, A S

    2015-01-01

    The article presents the results of the first domestic experience of intraoperative fluorescence mapping of sentinel lymph nodes in lung cancer. The research included 10 patients, who underwent surgery over the period of time from September 2013 to May 2014. After performing thoracotomy, the solution of indocyanine green (ICG) was injected using subpleural position above the tumor in 3-4 points. Fluorescence (ICG) image guided surgery was carried out by using infrared radiation (wave length 808 nm) on lung surface, root of lung, mediastinum in real time. Fluorescence lymph nodes were mapped. In case that metastatic lesions weren't revealed in sentinel lymph nodes, they weren't noted in other nodes. Method specificity consisted of 100%. Biopsy and histological study of sentinel lymph nodes mapped during fluorescence (ICG) image guided surgery could be useful for prevention of lymphodissection in patients with non-small cell carcinoma of lung. PMID:26601511

  17. Nanoparticle Albumin-bound Paclitaxel+Carboplatin Therapy for Small Cell Lung Cancer Combined with Squamous Cell Carcinoma and Interstitial Lung Disease.

    PubMed

    Azuma, Yuichiro; Tamiya, Motohiro; Shiroyama, Takayuki; Osa, Akio; Takeoka, Sawa; Morishita, Naoko; Suzuki, Hidekazu; Okamoto, Norio; Hirashima, Tomonori; Kawase, Ichiro

    2015-01-01

    It has recently been shown that nanoparticle albumin-bound paclitaxel (nab-PAC)+carboplatin (CBDCA) provides a favorable overall response rate in non-small cell lung cancer. This is the first case report of nab-PAC+CBDCA therapy in small cell lung cancer (SCLC). Our patient was a 72-year-old man with stage IV SCLC combined with squamous cell carcinoma and interstitial lung disease (ILD). We administered nab-PAC+CBDCA as a second-line chemotherapy. A partial response was evident after two cycles of chemotherapy, and no serious side effects occurred. The progression-free survival was 15 weeks. Second-line chemotherapy using nab-PAC+CBDCA was effective and well tolerated in an SCLC patient with ILD. PMID:26568008

  18. Comparison of the effects of inhaled {sup 239}PuO{sub 2} and {beta}- emitting radionuclides on the incidence of lung carcinomas in laboratory animals

    SciTech Connect

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

    1991-12-31

    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 {sup 239}PuO{sub 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{sup 4} Gy for beta emitters was 60 for rats and 65 for dogs, and for {sup 239}PuO{sub 2} it was 1500 for rats and 2300 for dogs.

  19. A rare case of human pulmonary dirofilariasis with a growing pulmonary nodule after migrating infiltration shadows, mimicking primary lung carcinoma

    PubMed Central

    Haro, Akira; Tamiya, Sadafumi; Nagashima, Akira

    2016-01-01

    Introduction Pulmonary dirofilariasis is a rare pulmonary parasitic infection by the nematode Dirofilaria immitis. It is characterized by an asymptomatic pulmonary nodule usually seen on chest X-ray. The differential diagnosis of pulmonary dirofilariasis includes other pulmonary diseases, primary lung carcinoma and metastatic lung tumor. Case presentation Pulmonary dirofilariasis was diagnosed in a woman who presented with interstitial pneumonia. Growth of the pulmonary nodule was detected subsequent to hemoptysis. The histological diagnosis was made based on a wedge resection performed under video-associated thoracic surgery (VATS). Conclusion Pulmonary dirofilariasis often varies in its clinical course. The diagnosis is best made using wedge resection under VATS. PMID:27015012

  20. Effect of some polysaccharides in cyclic nucleotide level and phosphodiesterase activity in organs of mice with lewis' lung carcinoma

    SciTech Connect

    Veksler, I.G.; Antonenko, S.G.

    1986-04-01

    This paper describes the results of a study of the effect of the bacterial polysaccharide prodigiosan and the yeast cell membrane bipolymer zymosan on the absolute and relative levels of cAMP, cAMP, and cAMP-dependent phosphodiesterase (PDE) in the thymus, spleen, and lungs of healthy mice and of mice with metastasizing Lewis' lung carcinoma. The cyclic nucleotide concentration was determined by radioimmunoassay. Radioactivity of the samples was studied in an SL-30 liquid scintillation counter. PDE activity was determined by paper chromatography using 8-/sup 3/H-cAMP as the substrate.

  1. Detection and treatment of lung metastases of differentiated thyroid carcinoma in patients with normal chest X-rays

    SciTech Connect

    Schlumberger, M.; Arcangioli, O.; Piekarski, J.D.; Tubiana, M.; Parmentier, C.

    1988-11-01

    Lung metastases were demonstrated by total-body /sup 131/I scans in 23 patients with differentiated thyroid carcinoma, at a time when chest x-ray was normal. This total-body /sup 131/I scan was performed after the administration of 2 mCi (in 11 patients) or 100 mCi (in 12 patients). Overall uptake of 131I in lungs was less than 1% of the administered dose in 11 patients. All patients were treated with radioiodine. No lung uptake was found in 20 patients at the last 100 mCi post-therapy scan. Among them, Tg level became undetectable during T4 treatment in eight, lung CT scan showed the disappearance of the micronodules in seven, and lung biopsy did not show evidence of disease in two patients. No patient developed radiation lung fibrosis. In conclusion, favorable responses to radioiodine treatment were observed despite relatively low overall uptake, in relation to the small size of lung metastases. This provides high concentrations of radioiodine and therefore high radiation doses.

  2. Cisplatin and Etoposide With or Without Veliparib in Treating Patients With Extensive Stage Small Cell Lung Cancer or Metastatic Large Cell Neuroendocrine Non-small Cell Lung Cancer

    ClinicalTrials.gov

    2016-06-01

    Carcinoma of Unknown Primary Origin; Extensive Stage Small Cell Lung Carcinoma; Large Cell Lung Carcinoma; Neuroendocrine Carcinoma; Newly Diagnosed Carcinoma of Unknown Primary Origin; Stage IV Non-Small Cell Lung Cancer

  3. Serum MicroRNA-21 as a Diagnostic Marker for Lung Carcinoma: A Systematic Review and Meta-Analysis

    PubMed Central

    Yang, Xiaorong; Guo, Yanan; Du, Yane; Yang, Jinmei; Li, Shichao; Liu, Shengnan; Li, Ke; Zhang, Dechun

    2014-01-01

    Objectives MicroRNA-21 in serum is a promising marker for the diagnosis of lung carcinoma. A meta-analysis was performed to assess the diagnostic accuracy and clinical value of serum microRNA-21 in patients with lung carcinoma. Methods PubMed, EMBASE, Web of Knowledge (ISI), the Cochrane Library, Scopus, BioMed Central, Science Direct, China National Knowledge Infrastructure (CNKI), Wan Fang data and Technology of Chongqing (VIP) databases were searched to identify studies in English and Chinese that assessed the diagnostic value of serum miR-21 for lung carcinoma, from inception to 9 April 2014. Two independent investigators identified and extracted the study characteristics from all articles according to defined inclusion and exclusion criteria. Quality assessment of diagnostic accuracy studies (QUADAS) was used to score the quality of the eligible studies. Stata12 and Meta-DiSc software were used to test the heterogeneity and to perform the meta-analysis. Results Our search returned 1008 articles, of which seven fulfilled the inclusion criteria, accounting for 500 patients and 386 controls. Using random-effect model analysis, the summary assessments revealed that the mean sensitivity was 0.71% (95%CI: 57–82%) and specificity was 0.84% (95%CI: 76–89%). The area under the receiver operating characteristic curve was 0.86 (95%CI: 0.83–0.89). In addition, heterogeneity was clearly apparent but was not caused by the threshold effect, as shown by Meta-DiSc analysis. Conclusion The current evidence suggests that serum miR-21 can be rapidly measured in lung carcinoma patients and has potential diagnostic value with moderate sensitivity and specificity. Further prospective studies to assess the early stage diagnostic value are needed in the future. PMID:24865991

  4. Muscular pseudotumor of the breast following doxorubicin and radiation therapy for oat cell carcinoma of the lung

    SciTech Connect

    Wergowske, G.; Chang, J.C.; Marger, D.

    1982-12-01

    Two male patients developed muscular pseudotumor of the breast following combined treatment of radiation and chemotherapy with cyclophosphamide, doxorubicin, methotrexate and procarbazine for oat cell carcinoma of the lung. The pathologic findings of the biopsy specimens revealed muscle and capillary changes similar to previously reported myocardiotoxicity from doxorubicin and radiation therapy. Discussed is a possible additive or synergistic toxic effect of doxorubicin and radiation therapy in the development of muscular pseudotumor of the breast.

  5. Iodine-131 treatment and high-resolution CT: results in patients with lung metastases from differentiated thyroid carcinoma.

    PubMed

    Ilgan, Seyfettin; Karacalioglu, A Ozgur; Pabuscu, Yuksel; Atac, G Kaan; Arslan, Nuri; Ozturk, Emel; Gunalp, Bengul; Ozguven, M Ali

    2004-06-01

    Between 1984 and 2002, pulmonary metastases were detected in 42 (4%) out of 1,023 patients with differentiated thyroid carcinoma (DTC) in our department. The age at diagnosis ranged from 6 to 77 years. Lung metastases were diagnosed by both increased thyroglobulin (Tg) levels and positive uptake of iodine-131 on scans, and/or positive radiological findings. The primary tumours were histologically classified as papillary (30 patients), follicular (nine patients) and poorly differentiated (two tall cell, one insular carcinoma). The duration of follow-up ranged from 24 to 228 months. The end-results of the (131)I therapy were evaluated. The treatment of choice was (131)I therapy of metastases after total thyroidectomy plus lymph node dissection (if lymph node metastases were present). Applied single and total (131)I activities were 1.8-10.4 GBq and 5.5-43.7 GBq, respectively. Lung metastases were present at the time of diagnosis in 30 patients and developed during the follow-up period in the remaining 12. Twelve patients with extensive metastases died of thyroid carcinoma and another died due to secondary malignancy (malignant mesothelioma). Ten patients with lung metastases remain completely free of disease and are probably cured, while another seven were stable at the time of study. Three- and five-year survival rates were 86% (36/42) and 76% (32/42), respectively. To define the diagnostic value of high-resolution computed tomography (HRCT) and identify the distinctive features of lung metastases from DTC, 22 patients were further examined with HRCT within 2 weeks of the initial diagnosis of lung metastases and the results were compared with chest X-ray findings. HRCT detected metastases in 10 out of 14 patients with a normal chest X-ray and confirmed metastases in all patients with positive (n=5) and suspicious (n=3) chest X-ray. HRCT did not show any abnormalities in four patients with positive lung uptake on (131)I whole-body images. Stage of disease, existence

  6. NOTCH, ASCL1, p53 and RB alterations define an alternative pathway driving neuroendocrine and small cell lung carcinomas

    PubMed Central

    Meder, Lydia; König, Katharina; Ozretić, Luka; Schultheis, Anne M.; Ueckeroth, Frank; Ade, Carsten P.; Albus, Kerstin; Boehm, Diana; Rommerscheidt‐Fuss, Ursula; Florin, Alexandra; Buhl, Theresa; Hartmann, Wolfgang; Wolf, Jürgen; Merkelbach‐Bruse, Sabine; Eilers, Martin; Perner, Sven; Heukamp, Lukas C.

    2015-01-01

    Small cell lung cancers (SCLCs) and extrapulmonary small cell cancers (SCCs) are very aggressive tumors arising de novo as primary small cell cancer with characteristic genetic lesions in RB1 and TP53. Based on murine models, neuroendocrine stem cells of the terminal bronchioli have been postulated as the cellular origin of primary SCLC. However, both in lung and many other organs, combined small cell/non‐small cell tumors and secondary transitions from non‐small cell carcinomas upon cancer therapy to neuroendocrine and small cell tumors occur. We define features of “small cell‐ness” based on neuroendocrine markers, characteristic RB1 and TP53 mutations and small cell morphology. Furthermore, here we identify a pathway driving the pathogenesis of secondary SCLC involving inactivating NOTCH mutations, activation of the NOTCH target ASCL1 and canonical WNT‐signaling in the context of mutual bi‐allelic RB1 and TP53 lesions. Additionaly, we explored ASCL1 dependent RB inactivation by phosphorylation, which is reversible by CDK5 inhibition. We experimentally verify the NOTCH‐ASCL1‐RB‐p53 signaling axis in vitro and validate its activation by genetic alterations in vivo. We analyzed clinical tumor samples including SCLC, SCC and pulmonary large cell neuroendocrine carcinomas and adenocarcinomas using amplicon‐based Next Generation Sequencing, immunohistochemistry and fluorescence in situ hybridization. In conclusion, we identified a novel pathway underlying rare secondary SCLC which may drive small cell carcinomas in organs other than lung, as well. PMID:26340530

  7. NOTCH, ASCL1, p53 and RB alterations define an alternative pathway driving neuroendocrine and small cell lung carcinomas.

    PubMed

    Meder, Lydia; König, Katharina; Ozretić, Luka; Schultheis, Anne M; Ueckeroth, Frank; Ade, Carsten P; Albus, Kerstin; Boehm, Diana; Rommerscheidt-Fuss, Ursula; Florin, Alexandra; Buhl, Theresa; Hartmann, Wolfgang; Wolf, Jürgen; Merkelbach-Bruse, Sabine; Eilers, Martin; Perner, Sven; Heukamp, Lukas C; Buettner, Reinhard

    2016-02-15

    Small cell lung cancers (SCLCs) and extrapulmonary small cell cancers (SCCs) are very aggressive tumors arising de novo as primary small cell cancer with characteristic genetic lesions in RB1 and TP53. Based on murine models, neuroendocrine stem cells of the terminal bronchioli have been postulated as the cellular origin of primary SCLC. However, both in lung and many other organs, combined small cell/non-small cell tumors and secondary transitions from non-small cell carcinomas upon cancer therapy to neuroendocrine and small cell tumors occur. We define features of "small cell-ness" based on neuroendocrine markers, characteristic RB1 and TP53 mutations and small cell morphology. Furthermore, here we identify a pathway driving the pathogenesis of secondary SCLC involving inactivating NOTCH mutations, activation of the NOTCH target ASCL1 and canonical WNT-signaling in the context of mutual bi-allelic RB1 and TP53 lesions. Additionally, we explored ASCL1 dependent RB inactivation by phosphorylation, which is reversible by CDK5 inhibition. We experimentally verify the NOTCH-ASCL1-RB-p53 signaling axis in vitro and validate its activation by genetic alterations in vivo. We analyzed clinical tumor samples including SCLC, SCC and pulmonary large cell neuroendocrine carcinomas and adenocarcinomas using amplicon-based Next Generation Sequencing, immunohistochemistry and fluorescence in situ hybridization. In conclusion, we identified a novel pathway underlying rare secondary SCLC which may drive small cell carcinomas in organs other than lung, as well. PMID:26340530

  8. Expression of MMP-2 correlates with increased angiogenesis in CNS metastasis of lung carcinoma

    PubMed Central

    Rojiani, Mumtaz V; Alidina, Janeen; Esposito, Nicole; Rojiani, Amyn M

    2010-01-01

    Matrix metalloproteinases (MMP) have been implicated in increased invasive and metastatic potential of tumors, possibly via interactions with the extracellular matrix and angiogenesis. This study investigates the relationship between MMP-2 immunoexpression and angiogenesis in a series of lung carcinomas metastatic to the central nervous system (CNS). Twenty eight metastatic carcinoma cases with adequate brain-tumor interface were identified from the archives at the Moffitt Cancer Center. MMP-2 expression was determined by immunohistochemistry using an antibody directed against pro and active forms (NeoMarkers). Similarly, microvessels were identified on parallel sections with anti-CD34 antibody (Biogenix). Angiogenesis profiles within the tumor and at the CNS/tumor interface were morphometrically assessed by the Image Pro Plus image analysis system. Briefly, CD34 positive vessels were quantitated and correlated with presence or absence of MMP-2 expression in the tumor. Mean microvessel area (MMVA) and mean microvessel number (MMVN) were assessed within areas of brain-tumor interface and within the tumor and expressed as a ratio relative to the tumor. Sixteen (57.14%) metastatic tumors were strongly immunoreac-tive for MMP-2, while 12 (42.86%) were negative. MMP-2 positive tumors had a higher MMVA and MMVN ratio at the CNS/tumor interface in comparison to MMP-2 negative neoplasms. MMP-2 expression thus appears to confer enhanced vascular proliferation particularly at the brain-tumor interface which would support the contention of enhanced capability of growth and invasion within the CNS, possibly modulated by MMP2. The relationship between MMP-2 expression and angiogenesis has been previously reported and its biological and therapeutic implications remain the focus of investigations. PMID:21151391

  9. Expression of MMP-2 correlates with increased angiogenesis in CNS metastasis of lung carcinoma.

    PubMed

    Rojiani, Mumtaz V; Alidina, Janeen; Esposito, Nicole; Rojiani, Amyn M

    2010-01-01

    Matrix metalloproteinases (MMP) have been implicated in increased invasive and metastatic potential of tumors, possibly via interactions with the extracellular matrix and angiogenesis. This study investigates the relationship between MMP-2 immunoexpression and angiogenesis in a series of lung carcinomas metastatic to the central nervous system (CNS). Twenty eight metastatic carcinoma cases with adequate brain-tumor interface were identified from the archives at the Moffitt Cancer Center. MMP-2 expression was determined by immunohistochemistry using an antibody directed against pro and active forms (NeoMarkers). Similarly, microvessels were identified on parallel sections with anti-CD34 antibody (Biogenix). Angiogenesis profiles within the tumor and at the CNS/tumor interface were morphometrically assessed by the Image Pro Plus image analysis system. Briefly, CD34 positive vessels were quantitated and correlated with presence or absence of MMP-2 expression in the tumor. Mean microvessel area (MMVA) and mean microvessel number (MMVN) were assessed within areas of brain-tumor interface and within the tumor and expressed as a ratio relative to the tumor. Sixteen (57.14%) metastatic tumors were strongly immunoreac-tive for MMP-2, while 12 (42.86%) were negative. MMP-2 positive tumors had a higher MMVA and MMVN ratio at the CNS/tumor interface in comparison to MMP-2 negative neoplasms. MMP-2 expression thus appears to confer enhanced vascular proliferation particularly at the brain-tumor interface which would support the contention of enhanced capability of growth and invasion within the CNS, possibly modulated by MMP2. The relationship between MMP-2 expression and angiogenesis has been previously reported and its biological and therapeutic implications remain the focus of investigations. PMID:21151391

  10. [TNM staging system of lung carcinoma: historical notes, limitations and controversies].

    PubMed

    Motta, G; Nahum, M A; Testa, T; Spinelli, E

    1995-01-01

    The TNM System as originally proposed by Denoix in 1946, provides a consistent, reproducible description of the anatomic extent of disease in cancer patients at a specific time in the life history of the cancer. C.F. Mountain first adapted this classification to lung cancer in 1973 on behalf of AJCC. In 1986 he presented the "New Intl. Staging System for Lung Cancers" mainly based on a 13 yr experience of the previous one, which was accepted world-wide through a round of international consensus meetings held in 1985. Clinical Staging is the best estimate of disease extent made prior to the institution of any therapy; Surgical-pathological Staging is the classification of disease extent as determined from pathological examination of resected specimens. Accordingly, once the diagnosis is made, it is necessary to stage accurately the tumour determining the size and location of the tumour (T status), the presence or absence of lymphnode involvement (N status), and whether the tumour is metastatic to distant sites (M status). Moreover the uniform staging criteria for lung cancer will assure for each patient the better selection of treatment, the evaluation of operability, the need for adjuvant therapy, as well as the estimation of prognosis. Equally important is the resultant ability to compare the outcome of treatment protocols from different centres. More recently C.F. Mountain has added to the Staging System a new standard logic or "convention" for classifying infrequently observed presentations of lung cancer with which the standard rules of Staging System itself don't fit. These conventions are based on empiric expectation for treatment selection and survival that are similar to those for the Staging definitions, which are based on actuarialsurvival data. Many different types of tumour such as multiple masses, synchronous multiple primitives, discontinuous tumour foci in visceral or parietal pleura as well neoplastic involvement of various mediastinal structures

  11. Enhancement of radiation effects by pXLG-mEndo in a lung carcinoma model

    SciTech Connect

    Luo Xian; Slater, James M.; Gridley, Daila S. . E-mail: dgridley@dominion.llumc.edu

    2005-10-01

    Purpose: Endostatin is a potent antiangiogenesis protein with little or no toxicity that has potential to enhance radiotherapy. The major goal of this study was to evaluate the combination of radiation and endostatin gene therapy in a preclinical lung cancer model. Methods: Plasmid pXLG-mEndo, constructed in our laboratory, includes the mouse endostatin gene cloned into the pWS4 vector. The kinetics of endostatin expression and efficacy of the pXLG-mEndo and radiation ({sup 60}Co {gamma}-rays) combination was evaluated in the C57BL/6 mouse-Lewis lung carcinoma (LLC) model. The LLC cells were implanted s.c. and pXLG-mEndo was injected intratumorally 12-14 days later without any transfection agent; a dose of 10 Gy radiation was applied approximately 16 h thereafter. Some groups received each modality twice. Endostatin, vascular endothelial growth factor (VEGF), and transforming growth factor-{beta}1 (TGF-{beta}1) were quantified in plasma and tumors, and tumor vasculature was examined. Results: Endostatin expression within LLC tumors peaked on Day 7 after pXLG-mEndo injection. Addition of radiation to pXLG-mEndo significantly enhanced the level of tumor endostatin compared with plasmid alone (p < 0.05). Tumor growth was significantly delayed in mice receiving pXLG-mEndo plus radiation compared with no treatment (p < 0.005), radiation (p < 0.05), and control plasmid (p < 0.05). The number of LLC tumor vessels was reduced after combined treatment (p < 0.05), and significant treatment-related changes were observed in both VEGF and TGF-{beta}1. Conclusions: The data demonstrate that delivery of endostatin by pXLG-mEndo as an adjuvant to radiation can significantly enhance the antitumor efficacy of radiotherapy in the LLC mouse tumor model and support further investigation of this unique combination therapy.

  12. Low doses of prophylactic cranial irradiation effective in limited stage small cell carcinoma of the lung

    SciTech Connect

    Rubenstein, J.H.; Dosoretz, D.E.; Katin, M.J. |

    1995-09-30

    Prophylactic cranial irradiation (PCI) for the prevention of brain metastasis in small cell lung cancer remains controversial, both in terms of efficacy and the optimal dose-fractionation scheme. We performed this study to evaluate the efficacy of PCI at low doses. One hundred and ninety-seven patients were referred to our institution for treatment of limited stage small cell carcinoma of the lung between June 1986 and December 1992. Follow-up ranged from 1.1 to 89.8 months, with a mean of 19 months. Eighty-five patients received PCI. Patients receiving PCI exhibited brain failure in 15%, while 38 of untreated patients developed metastases. This degree of prophylaxis was achieved with a median total dose of 25.20 Gy and a median fraction size of 1.80 Gy. At these doses, acute and late complications were minimal. Patients receiving PCI had significantly better 1-year and 2-year overall survivals (68% and 46% vs. 33% and 13%). However, patients with a complete response (CR) to chemotherapy and better Karnofsky performance status (KPS) were overrepresented in the PCI group. In an attempt to compare similar patients in both groups (PCI vs. no PCI), only patients with KPS {ge} 80, CR or near-CR to chemotherapy, and treatment with attempt to cure, were compared. In this good prognostic group, survival was still better in the PCI group (p = 0.0018). In this patient population, relatively low doses of PCI have accomplished a significant reduction in the incidence of brain metastasis with little toxicity. Whether such treatment truly improves survival awaits the results of additional prospective randomized trials. 44 refs., 4 figs., 2 tabs.

  13. A Coin-Like Peripheral Small Cell Lung Carcinoma Associated with Acute Paraneoplastic Axonal Guillain-Barre-Like Syndrome

    PubMed Central

    Jung, Ioan; Gurzu, Simona; Balasa, Rodica; Motataianu, Anca; Contac, Anca Otilia; Halmaciu, Ioana; Popescu, Septimiu; Simu, Iunius

    2015-01-01

    Abstract A 65-year-old previously healthy male heavy smoker was hospitalized with a 2-week history of progressive muscle weakness in the lower and upper extremities. After 10 days of hospitalization, urinary sphincter incompetence and fecal incontinence were added and tetraparesis was established. The computer-tomography scan examination revealed a massive right hydrothorax and multifocal solid acinar structures with peripheral localization in the left lung, which suggested pulmonary cancer. Bone marrow metastases were also suspected. Based on the examination results, the final diagnosis was acute paraneoplastic axonal Guillain-Barre-like syndrome. The patient died 3 weeks after hospitalization. At autopsy, bronchopneumonia and a right hydrothorax were confirmed. Several 4 to 5-mm-sized round peripherally located white nodules were identified in the left lung, without any central tumor mass. Under microscope, a coin-shaped peripheral/subpleural small cell carcinoma was diagnosed, with generalized bone metastases. A huge thrombus in the abdominal aorta and acute pancreatitis was also seen at autopsy. This case highlights the difficulty of diagnosis of lung carcinomas and the necessity of a complex differential diagnosis of severe progressive ascending neuropathies. This is the 6th reported case of small cell lung cancer-associated acute Guillain-Barre-like syndrome and the first report about an association with a coin-like peripheral pattern. PMID:26039124

  14. A coin-like peripheral small cell lung carcinoma associated with acute paraneoplastic axonal Guillain-Barre-like syndrome.

    PubMed

    Jung, Ioan; Gurzu, Simona; Balasa, Rodica; Motataianu, Anca; Contac, Anca Otilia; Halmaciu, Ioana; Popescu, Septimiu; Simu, Iunius

    2015-06-01

    A 65-year-old previously healthy male heavy smoker was hospitalized with a 2-week history of progressive muscle weakness in the lower and upper extremities. After 10 days of hospitalization, urinary sphincter incompetence and fecal incontinence were added and tetraparesis was established. The computer-tomography scan examination revealed a massive right hydrothorax and multifocal solid acinar structures with peripheral localization in the left lung, which suggested pulmonary cancer. Bone marrow metastases were also suspected. Based on the examination results, the final diagnosis was acute paraneoplastic axonal Guillain-Barre-like syndrome. The patient died 3 weeks after hospitalization. At autopsy, bronchopneumonia and a right hydrothorax were confirmed. Several 4 to 5-mm-sized round peripherally located white nodules were identified in the left lung, without any central tumor mass. Under microscope, a coin-shaped peripheral/subpleural small cell carcinoma was diagnosed, with generalized bone metastases. A huge thrombus in the abdominal aorta and acute pancreatitis was also seen at autopsy. This case highlights the difficulty of diagnosis of lung carcinomas and the necessity of a complex differential diagnosis of severe progressive ascending neuropathies. This is the 6th reported case of small cell lung cancer-associated acute Guillain-Barre-like syndrome and the first report about an association with a coin-like peripheral pattern. PMID:26039124

  15. The promise of lung master protocol for squamous cell carcinoma: one trial to rule them all, one trial to find them…?

    PubMed Central

    Russell, Prudence Anne

    2015-01-01

    The recently initiated lung master protocol (Lung-MAP) trial provides hope that the successes of targeted molecular therapy in lung adenocarcinoma can be extended to squamous cell carcinoma (SCC). It also is a template for rapid translation of clinical research through regulatory approval to clinical practice. This is vital in cancers with multiple possible oncogenic genomic aberrations, for which clinical trials would be too costly and impractical to conduct for individual targets making up less than 10% of cases. PMID:26488015

  16. Mitochondria in Lewis lung carcinoma cells under the effect of magnetosensitive nanocomplex and radiofrequency hyperthermia.

    PubMed

    Orel, V E; Grabovoy, A N; Romanov, A V; Kharkevich, N A; Schepotin, I B

    2013-08-01

    Electron microscopic study of Lewis lung carcinoma cell mitochondria after intravenous injection of a magnetosensitive nanocomplex based on ferric oxide (Fe3O4) nanoparticles and doxorubicin followed by radiofrequency hyperthermia showed that a common increase of the electron density of the cytoplasm was paralleled by mitochondrial edema in comparison with organelles of animals receiving doxorubicin alone. These changes were accompanied by virtually total lysis of the cristae and sharp clarification of mitochondrial matrix, which was seen from appreciable increase in mitochondria image brightness. Morphometric analysis showed lesser perimeter, area, and mean radius of the tumor cell mitochondria in animals receiving the injection of magnetosensitive nanocomplex and exposed to radiofrequency hyperthermia in comparison with those injected with doxorubicin alone. Histograms of distribution of the perimeter, area, and mean radius of the mitochondria after combined exposure to the nanocomplex and hyperthermia showed bimodal asymmetrical distribution. Injection of the magnetosensitive nanocomplex followed by radiosensitive hyperthermia led to more significant impairment of the tumor cell mitochondrial ultrastructure than doxorubicin alone. PMID:24143374

  17. Clinical trials with cyclophosphamide and misonidazole combination for maintaining treatment after radiation therapy of lung carcinoma

    SciTech Connect

    Busutti, L.; Breccia, A.; Stagni, G.; Gattavecchia

    1984-09-01

    Fifteen patients with inoperable non oat cell lung carcinoma, who had already been treated with telecobalt therapy in the mediastinum-hilar region, were treated with continuing therapy with misonidazole (MISO) and cyclophosphamide (Cy). MISO was administered in single doses of 1000 mg/m/sup 2/ and 500 mg/m/sup 2/, orally. Cy was administered in single doses of 500 mg/m/sup 2/ and 250 mg/m/sup 2/, i.v. This treatment was given every 4 weeks. All patients (15/15) suffered from hyporexia, nausea and vomiting within 48 hours from administration; furthermore, 2 patients had hemoragic cystitis, 2 had peripheral neurotoxicity, 3 had fever, and 2 had serious nervous depression. Leukopenia occurred in all patients immediately after drug administration, although it was not present in any patient by the time of the next administration. This clinical trial was concluded in December 1981. The follow-up at 18 months shows 7/15 cases of relapse. Eight of 15 patients are alive with progression of disease from 8 to 18 months.

  18. Molecular targeted therapy to improve radiotherapeutic outcomes for non-small cell lung carcinoma

    PubMed Central

    Bhardwaj, Bhaskar; Bhardwaj, Himanshu; Balusu, Sree; Shwaiki, Ali

    2016-01-01

    Effective treatments for non-small cell lung carcinoma (NSCLC) remain elusive. The use of concurrent chemotherapy with radiotherapy (RT) has improved outcomes, but a significant proportion of NSCLC patients are too frail to be able to tolerate an intense course of concurrent chemoradiotherapy. The development of targeted therapies ignited new hope in enhancing radiotherapeutic outcomes. The use of targeted therapies against the epidermal growth factor receptor (EGFR) has offered slight but significant benefits in concurrent use with RT for certain patients in certain situations. However, despite theoretical promise, the use of anti-angiogenics, such as bevacizumab and endostatin, has not proven clinically safe or useful in combination with RT. However, many new targeted agents against new targets are being experimented for combined use with RT. It is hoped that these agents may provide a significant breakthrough in the radiotherapeutic management of NSCLC. The current review provides a brief discussion about the targets, the targeted therapies, the rationale for the use of targeted therapies in combination with RT, and a brief review of the existing data on the subject. PMID:26904572

  19. Clinical potential of necitumumab in non-small cell lung carcinoma

    PubMed Central

    Genova, Carlo; Hirsch, Fred R

    2016-01-01

    Despite significant progress, new therapeutic approaches for advanced non-small cell lung cancer (NSCLC) are highly needed, particularly for the treatment of patients with squamous cell carcinoma. The epidermal growth factor receptor (EGFR) is often overexpressed in NSCLC and represents a relevant target for specific treatments. Although EGFR mutations are more frequent in non-squamous histology, the receptor itself is more often overexpressed in squamous NSCLC. Necitumumab is a human monoclonal antibody that is able to inhibit the EGFR pathway and cause antibody-dependent cell cytotoxicity. This drug has been studied in combination with first-line chemotherapy for advanced NSCLC in two Phase III trials, and a significant survival benefit was reported in squamous NSCLC (SQUIRE trial); by contrast, necitumumab did not prove itself beneficial in non-squamous histotype (INSPIRE trial). On the basis of the SQUIRE results, necitumumab was approved in combination with cisplatin and gemcitabine as a first-line treatment for advanced squamous NSCLC, both in the US and Europe, where its availability is limited to patients with EGFR-expressing tumors. The aim of this review is to describe the tolerability and the efficacy of necitumumab by searching the available published data and define its potential role in the current landscape of NSCLC treatment. PMID:27621656

  20. Deterministic and Stochastic Study for a Microscopic Angiogenesis Model: Applications to the Lewis Lung Carcinoma

    PubMed Central

    Bodnar, Marek; Piotrowska, Monika J.

    2016-01-01

    Angiogenesis modelling is an important tool to understand the underlying mechanisms yielding tumour growth. Nevertheless, there is usually a gap between models and experimental data. We propose a model based on the intrinsic microscopic reactions defining the angiogenesis process to link experimental data with previous macroscopic models. The microscopic characterisation can describe the macroscopic behaviour of the tumour, which stability analysis reveals a set of predicted tumour states involving different morphologies. Additionally, the microscopic description also gives a framework to study the intrinsic stochasticity of the reactive system through the resulting Langevin equation. To follow the goal of the paper, we use available experimental information on the Lewis lung carcinoma to infer meaningful parameters for the model that are able to describe the different stages of the tumour growth. Finally we explore the predictive capabilities of the fitted model by showing that fluctuations are determinant for the survival of the tumour during the first week and that available treatments can give raise to new stable tumour dormant states with a reduced vascular network. PMID:27182891

  1. Acute secondary effects in the esophagus in patients undergoing radiotherapy for carcinoma of the lung

    SciTech Connect

    Mascarenhas, F.; Silvestre, M.E.; Sa da Costa, M.; Grima, N.; Campos, C.; Chaves, P.

    1989-02-01

    The incidence and nature of acute secondary irradiation esophagitis was studied in a series of 38 patients undergoing 60Co teletherapy for carcinoma of the lung. Thirty-four patients were male and four female, with ages ranging from 38 to 78 years. The mediastinum being irradiated in the process, all the patients underwent endoscopy for signs of esophagitis and/or gastritis after a dose of 30-40 Gy was delivered to the esophagus. Eighteen patients complained of dysphagia, but only in 12 of them did endoscopy show esophagitis. Of the remaining patients without complaints five had endoscopic signs of esophagitis. Gastritis was found in 18 cases and confirmed histologically in 14. In 17 cases, esophagitis and/or gastritis were confirmed histologically. It is believed that there is a fairly close correlation among clinical, endoscopic, and histological findings to support the claim that esophagitis in these patients is radiation induced. However, the cause of gastritis is not well understood. Data in the literature suggest that nonsteroid anti-inflammatory agents can act as prophylactic means of preventing radiation esophagitis.

  2. Anti-metastatic effects of antrodan, the Antrodia cinnamomea mycelia glycoprotein, in lung carcinoma cells.

    PubMed

    Fa, Kuan-Ning; Yang, Chih-Min; Chen, Pei-Chun; Lee, Yin-Ying; Chyau, Charng-Cherng; Hu, Miao-Lin

    2015-03-01

    This study investigated the anti-metastatic effects of antrodan, the glycoprotein from Antrodia cinnamomea (AC) mycelia, through direct actions and indirect immunomodulatory effects in Lewis lung carcinoma (LLC). Antrodan was isolated from AC mycelia by alkali extraction, acid precipitation, and purification using sepharose CL-6B column chromatography. In the direct anti-metastatic action, antrodan (30-70 μg/mL) was found to significantly inhibit invasion and migration of LLC cells, and these effects involved up-regulation of tissue inhibitor of matrix metalloproteinase (TIMP)-1, TIMP-2, and nm23-H1 protein expression leading to decreased activities and protein expression of MMP-2 and MMP-9. For testing the indirect immunomodulatory effect, antrodan was incubated for 3d with mononuclear cells (MNCs) isolated from human peripheral blood to obtain the condition medium (CM). Antrodan significantly increased interleukin (IL)-12 and IL-1β levels, but decreased TNF-α, IL-6 and IL-8 levels in the MMC-CM, which also significantly inhibited invasion, migration, and the activities and protein expression of MMP-2 and MMP-9, but significantly increased protein expression of TIMP-1, TIMP-2, and nm23-H1 in LLC cells. The indirect immunomodulatory effect of antrodan was stronger than the direct anti-metastatic effect at the same concentrations (50 and 60 μg/mL). Overall, the results suggest the anti-metastatic potential of antrodan in LLC cells. PMID:25583024

  3. VP16-213 in combined modality treatment of small cell carcinoma of the lung.

    PubMed

    Newman, S B; Bitran, J D; Golomb, H M; Hoffman, P C; DeMeester, T R; Raghavan, V

    1982-04-01

    Thirty-four previously untreated patients with histologically proven small cell carcinoma of the lung were treated with a combined modality therapy program that incorporated VP16-213, an epipodophyllotoxin derivative, into the chemotherapy regimen. Initial therapy for two cycles was with V-CAM, VP16-213, cyclophosphamide, doxorubicin and methotrexate. Following two cycles of V-CAM each patient received radiation therapy consisting of 4000 rads to the primary site, both hila and the mediastinum, as well as 2000 rads as prophylaxis to the whole brain. After a one-week rest period the patients received monthly cycles of V-CAM until death. Of 10 patients with stage IIIM0 disease, 7 had a complete response (CR), 1 a partial response (PR) and 2 had progressive disease. The median survival was still not reached by approximately 18 months. Of 24 patients with supraclavicular and/or metastatic disease there were only 5 patients with a CR, 11 with a PR and 8 with progressive disease. Their median survival was approximately 9 months. The 70% overall response rate and 9.3-month median survival of the entire group are essentially the same results as those in previously reported studies. There appears to be no additional benefit when VP16-213 is incorporated into our combined modality program. PMID:6288390

  4. Cancer Signature Investigation: ERBB2 (HER2)-Activating Mutation and Amplification-Positive Breast Carcinoma Mimicking Lung Primary.

    PubMed

    Shih, Jennifer; Bashir, Babar; Gustafson, Karen S; Andrake, Mark; Dunbrack, Roland L; Goldstein, Lori J; Boumber, Yanis

    2015-08-01

    Next-generation sequencing of primary and metachronous metastatic cancer lesions may impact patient care. We present a case of relapsed metastatic breast cancer with a dominant pulmonary lesion originally identified as lung adenocarcinoma. A 72-year-old, never-smoker woman with a protracted cough was found to have a large lung mass and regional lymphadenopathy on a chest CT. Lung mass biopsy showed adenocarcinoma with focal TTF-1 (thyroid transcription factor 1) positivity, favoring a lung primary. In addition to stereotactic brain radiation for cerebral metastases, she was started on carboplatin/pemetrexed. As part of the workup, the tumor was analyzed by a 50-gene targeted mutation panel, which detected 3 somatic mutations: ERBB2 (HER2) D769H activating missense mutation, TP53 Y126 inactivating truncating mutation, and SMARCB1 R374Q missense mutation. Of note, the patient had a history of stage IIA triple-negative grade 3 invasive ductal carcinoma of the left breast 1.5 years ago and received neoadjuvant chemotherapy and adjuvant radiation, and underwent a lumpectomy. Further analysis of her primary breast tumor showed a mutational profile identical to that of the lung tumor. Fluorescence in situ hybridization revealed HER2 amplification in the lung tumor, with a HER2/CEP17 ratio of 3.9. The patient was diagnosed with recurrent HER2-positive metastatic breast carcinoma with a coexisting ERBB2 (HER2) activating mutation. Chemotherapy was adjusted to include dual HER2-targeted therapy containing trastuzumab and pertuzumab, resulting in an ongoing partial response. This case demonstrates that a unique genetic mutational profile can clarify whether a tumor represents a metastatic lesion or new malignancy when conventional morphological and immunohistochemical methods are indeterminate, and can directly impact treatment decisions. PMID:26285240

  5. Feasibility and Clinical Value of CT-guided (125)I Brachytherapy for Bilateral Lung Recurrences from Colorectal Carcinoma.

    PubMed

    Wang, Guobao; Zhang, Fujun; Yang, Bin; Xue, Jingbing; Peng, Sheng; Zhong, Zhihui; Zhang, Tao; Lu, Mingjian; Gao, Fei

    2016-03-01

    Purpose To prospectively evaluate the feasibility and clinical value of computed tomography (CT)-guided iodine 125 ((125)I) brachytherapy to treat bilateral lung recurrences from colorectal carcinoma. Materials and Methods This study was approved by Sun Yat-sen University Cancer Center Institutional Review Board and all patients provided informed written consent. Seventy-two patients with bilateral lung recurrences from colorectal carcinoma were enrolled and randomly divided into two groups. Thirty-three were percutaneously treated with CT-guided (125)I brachytherapy (group A) and the other 39 were only given symptomatic and supportive treatments (group B). Follow-up contrast agent-enhanced CT scans were reviewed and efficacy of treatment was evaluated. (125)I brachytherapy was considered a success if it achieved the computerized treatment planning system criteria 1 month after procedure. Analyses included Kaplan-Meier, Mantel-Cox log-rank test, and Cox proportional hazards regression. Results In group A, 37 (125)I brachytherapy procedures were performed in 33 patients with 126 lung metastatic lesions and the success rate was 87.9% (29 of 33 patients). The local control rate of 3, 6, 12, 24, and 36 months was 75.8%, 51.5%, 33.3%, 24.2%, and 9.1%, respectively. A small amount of pulmonary hematoma occurred in five patients, and six patients presented with pneumothorax with pulmonary compression of 30%-40%. No massive bleeding or radiation pneumonitis occurred. The mean overall survival (OS) of group A was significantly longer than that of group B, and (125)I brachytherapy was an independent factor that affected the OS (group A, 18.8 months; group B, 8.6 months; hazard ratio, 0.391 [95% confidence interval: 0.196, 0.779]; P = .008). Conclusion CT-guided (125)I brachytherapy is feasible and safe for the treatment of bilateral lung recurrences from colorectal carcinoma. (©) RSNA, 2015. PMID:26406550

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

    PubMed

    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

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

    PubMed Central

    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

  8. Chemotherapy and Radiation Therapy With or Without Metformin Hydrochloride in Treating Patients With Stage III Non-small Cell Lung Cancer

    ClinicalTrials.gov

    2016-06-17

    Adenosquamous Lung Carcinoma; Bronchioloalveolar Carcinoma; Large Cell Lung Carcinoma; Lung Adenocarcinoma; Non-Small Cell Lung Carcinoma; Recurrent Non-Small Cell Lung Carcinoma; Squamous Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer

  9. Deguelin Induces the Apoptosis of Lung Squamous Cell Carcinoma Cells through Regulating the Expression of Galectin-1

    PubMed Central

    Yan, Bing; Zhao, Dejian; Yao, Yinan; Bao, Zhang; Lu, Guohua; Zhou, Jianying

    2016-01-01

    Lung cancer is the leading cause of cancer mortality around the world. Despite advances in the targeted therapy, patients with lung squamous cell carcinoma(SCC) still benefit few from it, and the search for potential effective therapies is imperative. Here, we demonstrated that deguelin induced significant apoptosis of lung SCC cells in vitro. Importantly, we found deguelin down-regulated the expression of galectin-1, which was involved in a wide range of tumorous physiologic process. Thus, we both over-expressed and down-regulated galectin-1 to perform its role in deguelin-induced apoptosis. We found that increased galectin-1 attenuated apoptosis of SCC cells exposed to deguelin, while galectin-1 knockdown sensitized lung cancer cells to deguelin treatment. Additionally, we observed that down-regulation of galectin-1 resulted in suppression of Ras/Raf/ERK pathway which was involved in deguelin-induced cell apoptosis. We also found that deguelin had a significant anti-tumor ability with decline of galectin-1 in vivo. In conclusion, these findings confirm that deguelin may act as a new chemo-preventive agent through inducing apoptosis of lung SCC cells in a galectin-1 dependent manner. PMID:27313498

  10. Genomic aberrations in squamous cell lung carcinoma related to lymph node or distant metastasis.

    PubMed

    Boelens, Mirjam C; Kok, Klaas; van der Vlies, Pieter; van der Vries, Gerben; Sietsma, Hannie; Timens, Wim; Postma, Dirkje S; Groen, Harry J M; van den Berg, Anke

    2009-12-01

    About 50% of patients presenting with resectable lung cancer develop distant metastases within 5 years. Genomic markers predicting metastatic behaviour of squamous cell lung carcinoma (SCC) are currently underexposed. We analyzed a cohort of patients with primary SCC using array-based comparative genomic hybridization (aCGH) to identify which genomic aberrations are related to metastatic behaviour. The cohort consisted of 34 patients with a follow-up of at least 5 years, 8 with metastases in regional lymph nodes only and 26 patients without any metastases at the time of surgery. Eleven of the latter 26 developed metastases in distant organs within 3 years after surgery. Copy number changes observed in at least 40% of all SCC included gains at chromosomal arms 3q, 5p, 8q, 19q, 20p, 22q and losses at 3p, 4p, 4q, 5q, 8p and 9p. High copy number amplifications were observed at 2p15-p16, 3q24-q29, 8p11-p12, 8q23-q24, and 12p12, containing candidate oncogenes such as BCL11A, REL, ECT2, PIK3CA, ADAM9, MYC and KRAS. Amplification of 2p15-p16 is a novel finding in SCC. Another novel finding is the homozygous deletion observed at 4q33-34.1 in 15% of the SCC cases. Gains at 7q36, 8p12, 10q22, 12p12, loss at 4p14 and the homozygous deletions at 4q occurred significantly more frequent in SCC from patients with lymph node metastases only. SCC from patients with distant metastases showed a significantly higher gain frequency at 8q22-q24 and loss at 8p23 and 13q21, and a significantly lower gain frequency at 2p12 and 2p16 and loss at 11q25 compared with SCC from patients without metastases. Of these, gains at 7q, 8p and 10q were restricted to SCC with lymph node metastasis and gain at 8q was restricted to patients with distant metastasis. Two genomic aberrations, i.e. loss of 4p and gain of 19q12 were observed more frequently in SCC with only lymph node metastases as compared to SCC with distant metastases. In conclusion, we identified genomic aberrations in primary SCC that were

  11. DETECTION OF HUMAN LUNG EPITHELIA CELL GROWTH FACTORS PRODUCED BY A LUNG CARCINOMA CELL LINE: USE IN CULTURE OF PRIMARY SOLID LUNG TUMORS

    EPA Science Inventory

    Serum-free medium conditioned for 72 h by a human undifferentiated adenocarcinoma of lung, Cal u 6, stimulated the colony formation of normal human bronchial epithelial cells, newly cultured cells from human solid lung tumors, and established human lung tumor cell lines, includin...

  12. Primary mixed squamous carcinoma and osteosarcoma (carcinosarcomas) of the lung have a CGH mapping similar to primitive squamous carcinomas and osteosarcomas.

    PubMed

    Pardo, Javier; Aisa, Gregorio; de Alava, Enrique; Sola, Jesús J; Panizo, Angel; Rodríguez-Spiteri, Natalia; García, Juan L; Torre, Wenceslao

    2008-09-01

    Carcinosarcomas are malignant tumors with a mixture of carcinomatous and differentiated sarcomatous elements. We investigate the morphology, immunohistochemistry, and comparative genomic hybridization analysis of 3 mixed squamous carcinoma and osteosarcoma of the lung. All patients were male and their ages were 72, 43, and 58 years. The sizes of the neoplasms were 7, 5, and 5 cm in maximum diameter, respectively. Two patients died of the disease 9 and 14 months after surgery; and one is alive 6 months later. By light microscopy, all cases had both squamous and osteosarcomatous structures. Immunohistochemistry was positive for AE3AE1, p63, 34 E12, CAM 5.2 (2/3 cases), CK-7 (2/3 cases), epithelial membrane antigen, E-cadherin, p53, and carcinogenic embryonic antigen in carcinomatous areas, and for vimentin and CD-68 in sarcomatous component. Areas of transition positive for both cytokeratins and vimentin were seen in all cases. A total of 55 copy number changes were detected with a median of 18 abnormalities per case: 48 gains, 6 losses, and 1 high-level amplification. Chromosome alterations in osteosarcomatous areas were similar to those found in lung metastatic osteosarcoma, comparable to those found in carcinomatous areas and to lung squamous carcinomas. Coincidences between carcinomatous areas and osteosarcomatous zones were found as gains in chromosomes 1q, 3q, 5p, 8q, and 12p. These findings provide arguments that favor a common origin for both types of cells, supported by the mixture of cells, the existence of undifferentiated cells positive to both cytokeratin and vimentin markers, and the CGH overlaps of chromosomal gains between carcinomatous and sarcomatous areas. PMID:18382357

  13. Combined high-grade neuroendocrine carcinoma of the lung: clinicopathological and immunohistochemical study of 34 surgically resected cases.

    PubMed

    Yamada, Kenji; Maeshima, Akiko Miyagi; Tsuta, Koji; Tsuda, Hitoshi

    2014-01-01

    To understand the pathogenesis of high-grade neuroendocrine carcinoma (HGNEC), we examined the histopathology and immunoreactivity against adenocarcinoma (AD), squamous cell carcinoma (SQ), and neuroendocrine markers in 34 cases with combined HGNEC. The 5 year overall survival rates of patients with combined small cell carcinoma (SCC) (n = 9) and combined large cell neuroendocrine carcinoma (LCNEC) (n = 25) were 33% and 75%, respectively (P = 0.011). Most of the patients were male (94%), smokers (94%), and had tumors located in the peripheral (94%) and upper lobe (65%) of the lung. Histopathologically, non-HGNEC components were predominantly ADs (65%) followed by SQs (26%). In combined HGNEC and AD, a lepidic AD component was found in 12 cases (48%). For the HGNEC components of combined HGNEC and AD, the incidence of positivity of thyroid transcription factor-1 (TTF-1) (8G7G3/1) and TTF1 (SPT24) were 64% and 91%, respectively. For HGNEC components of combined HGNEC and SQ, the incidence of positivity of 34βE12 and p63 were 22% and 11%, respectively. In conclusion, 48% of combined HGNEC and AD cases had a lepidic AD component, suggesting that HGNEC can develop in association with pre-existing AD. AD markers, but not SQ markers, were frequently retained through development of the HGNEC component. PMID:24471967

  14. 78 FR 53645 - Black Lung Benefits Act: Standards for Chest Radiographs

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-30

    ... of Workers' Compensation Programs 20 CFR Parts 718 and 725 RIN 1240-AA07 Black Lung Benefits Act: Standards for Chest Radiographs AGENCY: Office of Workers' Compensation Programs, Labor. ACTION: Direct final rule; withdrawal. SUMMARY: The Office of Workers' Compensation Programs (OWCP) published a...

  15. Lewis lung carcinoma regulation of mechanical stretch-induced protein synthesis in cultured myotubes.

    PubMed

    Gao, Song; Carson, James A

    2016-01-01

    Mechanical stretch can activate muscle and myotube protein synthesis through mammalian target of rapamycin complex 1 (mTORC1) signaling. While it has been established that tumor-derived cachectic factors can induce myotube wasting, the effect of this catabolic environment on myotube mechanical signaling has not been determined. We investigated whether media containing cachectic factors derived from Lewis lung carcinoma (LLC) can regulate the stretch induction of myotube protein synthesis. C2C12 myotubes preincubated in control or LLC-derived media were chronically stretched. Protein synthesis regulation by anabolic and catabolic signaling was then examined. In the control condition, stretch increased mTORC1 activity and protein synthesis. The LLC treatment decreased basal mTORC1 activity and protein synthesis and attenuated the stretch induction of protein synthesis. LLC media increased STAT3 and AMP-activated protein kinase phosphorylation in myotubes, independent of stretch. Both stretch and LLC independently increased ERK1/2, p38, and NF-κB phosphorylation. In LLC-treated myotubes, the inhibition of ERK1/2 and p38 rescued the stretch induction of protein synthesis. Interestingly, either leukemia inhibitory factor or glycoprotein 130 antibody administration caused further inhibition of mTORC1 signaling and protein synthesis in stretched myotubes. AMP-activated protein kinase inhibition increased basal mTORC1 signaling activity and protein synthesis in LLC-treated myotubes, but did not restore the stretch induction of protein synthesis. These results demonstrate that LLC-derived cachectic factors can dissociate stretch-induced signaling from protein synthesis through ERK1/2 and p38 signaling, and that glycoprotein 130 signaling is associated with the basal stretch response in myotubes. PMID:26491045

  16. The role of thoracic and cranial irradiation for small cell carcinoma of the lung

    SciTech Connect

    Cox, J.D.; Holoye, P.Y.; Byhardt, R.W.; Libnoch, J.A.; Komaki, R.; Hansen, R.M.; Kun, L.E.; Anderson, T.

    1982-02-01

    Since 1974, 120 previously untreated patients with small cell carcinoma of the lung seen in Therapeutic Radiology at The Medical College of Wisconsin have been entered into one of 4 successive studies. Study I used thoracic irradiation (TI) alone (4500-6000 rad in 3-6 weeks) with chemotherapy at progression. Study II randomized patients with limited disease to TI (3000 rad in 2 weeks) plus either cyclophosphamide, doxorubicin, vincristine (CAV) or total body irradiation (TBI); patients with extensive disease received TI + CAV. Study III employed prophylactic cranial irradiation (PCI) plus CAV and withheld TI unless there was incomplete response or recurrence. Of 93 evaluable patients from the first three studies, 55 had limited and 38 extensive disease. Study I (37 patients) showed a 62% complete response (CR) rate; 43% failed in the chest, 14% had brain metastases, and the median survival was only 22 weeks in spite of a preponderance of limited disease patients. Study II (27 patients) showed a CR of 59%; 30% had brain metastases and the median survival was 48 weeks. Study III patients (29) had a 69% rate; 72% failed in the chest, 4% with PCI developed brain metastases, and the median survival was 50 weeks. In March, 1979, Study IV was initiated; patients receive PCI (2500 rad in 2 weeks) plus high dose CAV, methotrexate and leucovorin. After 6 cycles, consolidation TI (3750 rad in 3 weeks) is given to patients with complete response. Preliminary results with 27 patients treated on this study show a 67% CR rate, a 41% chest failure rate (but onlyE 11% for the patients who received thoracic irradiation) and no intracranial failures, but a 13% extracranial CNS failure rate. PCI, TI and spinal irradiation may be necessary to maximize the probability of long term disease free survival.

  17. Induction of p53-independent growth inhibition in lung carcinoma cell A549 by gypenosides.

    PubMed

    Liu, Jung-Sen; Chiang, Tzu-Hsuan; Wang, Jinn-Shyan; Lin, Li-Ju; Chao, Wei-Chih; Inbaraj, Baskaran Stephen; Lu, Jyh-Feng; Chen, Bing-Huei

    2015-07-01

    The objectives of this study are to investigate antiproliferative effect and mechanisms of bioactive compounds from Gynostemma pentaphyllum (G. pentaphyllum) on lung carcinoma cell A549. Saponins, carotenoids and chlorophylls were extracted and fractionated by column chromatography, and were subjected to high-performance liquid chromatography-mass spectrometry analyses. The saponin fraction, which consisted mainly of gypenoside (Gyp) XXII and XXIII, rather than the carotenoid and chlorophyll ones, was effective in inhibiting A549 cell growth in a concentration- and a time-dependent manner as evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The estimated half maximal inhibitory concentration (IC50 ) of Gyp on A549 cells was 30.6 μg/ml. Gyp was further demonstrated to induce an apparent arrest of the A549 cell cycle at both the S phase and the G2/M phase, accompanied by a concentration- and a time-dependent increase in the proportions of both the early and late apoptotic cells. Furthermore, Gyp down-regulated cellular expression of cyclin A and B as well as BCL-2, while up-regulated the expression of BAX, DNA degradation factor 35 KD, poly [ADP-ribose] polymerase 1, p53, p21 and caspase-3. Nevertheless, both the treatment of a p53 inhibitor, pifithrin-α, and the small hairpin RNA-mediated p53 knockdown in the A549 cells did not alter the growth inhibition effect induced by Gyp. As a result, the cell cycle arrest and apoptosis of A549 cells induced by Gyp would most likely proceed through p53-independent pathway(s). PMID:25781909

  18. Induction of p53-independent growth inhibition in lung carcinoma cell A549 by gypenosides

    PubMed Central

    Liu, Jung-Sen; Chiang, Tzu-Hsuan; Wang, Jinn-Shyan; Lin, Li-Ju; Chao, Wei-Chih; Inbaraj, Baskaran Stephen; Lu, Jyh-Feng; Chen, Bing-Huei

    2015-01-01

    The objectives of this study are to investigate antiproliferative effect and mechanisms of bioactive compounds from Gynostemma pentaphyllum (G. pentaphyllum) on lung carcinoma cell A549. Saponins, carotenoids and chlorophylls were extracted and fractionated by column chromatography, and were subjected to high-performance liquid chromatography-mass spectrometry analyses. The saponin fraction, which consisted mainly of gypenoside (Gyp) XXII and XXIII, rather than the carotenoid and chlorophyll ones, was effective in inhibiting A549 cell growth in a concentration- and a time-dependent manner as evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The estimated half maximal inhibitory concentration (IC50) of Gyp on A549 cells was 30.6 μg/ml. Gyp was further demonstrated to induce an apparent arrest of the A549 cell cycle at both the S phase and the G2/M phase, accompanied by a concentration- and a time-dependent increase in the proportions of both the early and late apoptotic cells. Furthermore, Gyp down-regulated cellular expression of cyclin A and B as well as BCL-2, while up-regulated the expression of BAX, DNA degradation factor 35 KD, poly [ADP-ribose] polymerase 1, p53, p21 and caspase-3. Nevertheless, both the treatment of a p53 inhibitor, pifithrin-α, and the small hairpin RNA-mediated p53 knockdown in the A549 cells did not alter the growth inhibition effect induced by Gyp. As a result, the cell cycle arrest and apoptosis of A549 cells induced by Gyp would most likely proceed through p53-independent pathway(s). PMID:25781909

  19. An in vitro chemoresponse assay defines a subset of colorectal and lung carcinomas responsive to cetuximab.

    PubMed

    Rice, Shara D; Cassino, Theresa R; Sakhamuri, Lahari; Song, Nan; Williams, Karl E; Brower, Stacey L

    2011-01-15

    Cetuximab is a chimeric monoclonal antibody for the epidermal growth factor receptor (EGFR) that may provide benefit to select cancer patients; however, identification of the characteristics of those patients who may benefit from its use is not complete. The ChemoFx® drug response marker (DRM) is an in vitro assay that can provide drug response data on tumor specimens before any patient treatment is initiated. We determined the feasibility of using the ChemoFx DRM to test tumor samples for sensitivity to cetuximab. We exposed four non-small cell lung carcinoma (NSCLC) cell lines (H358, H520, HCC827, and H1666) to cetuximab and determined their sensitivity using the ChemoFx DRM and, in parallel, EGFR status using immunocytochemistry, Western blotting, and In-Cell Western (TM) analysis. We used the ChemoFx DRM to determine cetuximab sensitivity of primary NSCLC and colorectal tumor samples. The ChemoFx DRM distinguished between cetuximab-sensitive and -resistant cell lines. Cetuximab sensitivity was not dependent on EGFR mutational status; H358 cells were non-responsive to cetuximab yet contain wild-type EGFR, whereas H1666 cells were intermediately responsive to cetuximab and contain wild-type EGFR. HCC827 (EGFR-mutant) cells were intermediately responsive and, as expected, H520 cells (EGFR-null) were non-responsive to cetuximab. ChemoFx-determined cetuximab sensitivity of primary NSCLC and colorectal tumor samples was 9.0% and 7.5%, respectively. Use of the ChemoFx DRM is feasible for determining cetuximab sensitivity. The ChemoFx-determined cetuximab responses of primary NSCLC and colorectal tumor specimens were similar to published response rates of patients to treatment with cetuximab monotherapy. PMID:20980824

  20. Induction of highly immunogenic variants of Lewis lung carcinoma tumor by ultraviolet irradiation

    SciTech Connect

    Peppoloni, S.; Herberman, R.B.; Gorelik, E.

    1985-06-01

    This study was undertaken to determine whether in vitro treatment of Lewis lung carcinoma (3LL) cells with ultraviolet (UV) radiation could increase their immunogenicity. Tumor cells were irradiated with UV light from a germicidal lamp (254 nm; UV-C) at a dose of 720 J/sq m. After 2 weeks of culture, the surviving cell population was cloned by limiting dilution. Cell suspensions of each clone were injected intrafootpad in C57BL/6 mice at a dose of 2.5 X 10(5) cells per mouse. Eighty independent clones were tested. Fifty-one clones showed decreased tumorigenicity and failed to grow in 20 to 95% of immunocompetent mice, whereas they produced tumors in 100% of irradiated (550 R) and athymic nude mice. These clones were designated tum- (nontumorigenic) clones. In contrast, all 25 clones selected from the untreated parental 3LL induced progressively growing tumors in 100% of the mice. After two courses of UV treatment, the uncloned 3LL population was rejected in 45% of inoculated mice. Mice rejecting an inoculum of a tum- clone were completely resistant to subsequent challenge with higher doses of the same or unrelated tum- clones. This resistance was fully expressed even after irradiation of immune mice with 550 R. Mice immune to a tum- clone also were able to prevent the growth of various tum+ clones or untreated 3LL tumor cells. When tum- and tum+ clone cells were simultaneously inoculated intrafootpad in opposite legs, rejection of tum- clone resulted also in the prevention of the growth of tum+ clone. Spleen cells of immune mice caused rapid elimination of radiolabeled 3LL tumor cells from the place of their inoculation (intrafootpad) and prevented tumor growth.

  1. Buthionine sulfoximine inhibition of cystine uptake and glutathione biosynthesis in human lung carcinoma cells

    SciTech Connect

    Brodie, A.E.; Reed, D.J.

    1985-03-15

    Intracellular glutathione (GSH) content of human lung carcinoma cells, A549, in log phase was 25 +/- 5 nmol/10(6) cells, which is considerably higher than that reported in other tumor cells. After partial depletion of GSH with diethyl maleate (DEM), addition of cystine to the medium allowed full resynthesis of GSH in 4 hr, cysteine in the same time period led to less resynthesis, and methionine provided minimal resynthesis. Using cystine as the sole sulfur source and with buthionine sulfoximine (BSO, 5 mM) included in the medium after cells were depleted with DEM, inhibition of both cystine uptake and resynthesis of GSH occurred. BSO inhibited (/sup 35/S)cystine uptake (as early as 10 min) in a concentration-dependent process, ranging from a 28% decrease for 1 microM BSO to an 85% decrease for 100 microM BSO compared to the control cells after 240 min of incubation. In addition, GSH resynthesis from (/sup 35/S)cystine for 240 min was inhibited in a parallel dose-dependent manner, in that 1 microM BSO caused a 27% decrease and 100 microM BSO provided a 75% decrease from control values. BSO did not inhibit the uptake of (/sup 35/S)methionine, but inhibited the low amount of resynthesis of GSH when methionine was the sole sulfur source. BSO did not inhibit the uptake of arginine, phenylalanine, and leucine. DL-, L-, and methyl ester-BSO each inhibited (/sup 35/S)cystine uptake and incorporation into GSH to a similar extent. The half-life of GSH was 3.5 +/- 0.4 hr in A549 cells that were grown in complete medium with GSH synthesis occurring.

  2. Therapy of human non-small-cell lung carcinoma using antibody targeting of a modified superantigen.

    PubMed

    Forsberg, G; Ohlsson, L; Brodin, T; Björk, P; Lando, P A; Shaw, D; Stern, P L; Dohlsten, M

    2001-07-01

    Superantigens activate T-cells by linking the T-cell receptor to MHC class II on antigen-presenting cells, and novel reactivity can be introduced by fusing the superantigen to a targeting molecule. Thus, an antibody-targeted superantigen, which activates T cells to destroy tumour cells, might be used as cancer therapy. A suitable target is the 5T4 oncofetal antigen, which is expressed on many carcinomas. We constructed a fusion protein from a Fab of a monoclonal antibody recognizing the 5T4 antigen, and an engineered superantigen. The recombinant product 5T4FabV13-SEA(D227A)bound the 5T4 antigen expressed on the human non-small-cell lung cancer cell line Calu-1 with a Kd of 1.2 nM while the substitution of Asp227 to Ala in the superantigen moiety reduced binding activity to MHC class II. 5T4FabV13-SEA(D227A)tumour reactivity was demonstrated in 7/7 NSCLC samples by immunohistochemistry, while normal tissue reactivity was low to moderate. 5T4FabV13-SEA(D227A)induced significant T-cell-dependent in vitro killing of sensitive 5T4 bearing Calu-1 cells, with maximum lysis at 10(-10)M, while the capacity to lyse MHC class II expressing cells was approximately 1000 times less effective. Immunotherapy of 5T4FabV13-SEA(D227A)against human NSCLC was investigated in SCID mice reconstituted with human peripheral blood mononuclear cells. Mice carrying intreperitoneally growing Calu-1 cells showed significant reduction in tumour mass and number after intravenous therapy with 5T4FabV13-SEA(D227A). Thus, 5T4FabV13-SEA(D227A)has highly attractive properties for therapy of human NSCLC. PMID:11437414

  3. Inhibition of the growth of Lewis lung carcinoma by indomethacin in conventional, nude, and beige mice.

    PubMed

    Maca, R D

    1988-12-01

    The effects of a prostaglandin synthesis inhibitor, indomethacin (Indo), on the growth of Lewis lung carcinoma (LLC) growing as primary subcutaneous tumors in either conventional C57BL/6 mice, T cell deficient nude mice, or natural killer (NK) cell deficient beige mice were studied. In conventional mice, Indo, when continuously administered in the drinking water, consistently and significantly inhibited, in a dose-related fashion, the growth of LLC implanted either subcutaneously in the footpad or in the inguinal region; however, the degree of inhibition of footpad tumor appeared to be greater than that of inguinal tumor. Maximum inhibition was found when Indo was initiated before detectable or measurable tumor developed. If Indo treatment was initiated after tumor growth was evident, then Indo was found to be less effective, although significant inhibition was still observed. Indo also effectively inhibited LLC growing either in the footpad or in the inguinal region of nude or beige mice. The degree of inhibition of both footpad and inguinal tumors in both these mice was comparable to that seen in conventional C57BL/6 mice, indicating that mature T cells, NK cells, or soluble products produced only by these cells are not involved in mediating or modulating the inhibitory effects of Indo on LLC growth. Although Indo treatment significantly inhibited LLC growth in vivo, continuous treatment of cultured LLC cells with Indo in vitro did not decrease the growth of cultured cells. These results indicate that the inhibitory effect of Indo in vivo is not the result of a direct inhibitory effect of Indo on these tumor cells. Lastly, this inhibitory effect of Indo in vivo could not be reversed or negated, not even in part, by the simultaneous, daily i.p. administration of 16,16-dimethyl-PGE2. This finding suggests that the inhibitory effect of Indo involves a mechanism other than the inhibition of prostaglandin E2 production. PMID:3216222

  4. Molecularly targeted therapies for advanced or metastatic non-small-cell lung carcinoma

    PubMed Central

    Bayraktar, Soley; Rocha-Lima, Caio M

    2013-01-01

    Non-small-cell lung cancer (NSCLC) remains the leading cause of cancer-related death in both men and women in the United States. Platinum-based doublet chemotherapy has been a standard for patients with advanced stage disease. Improvements in overall survival and quality of life have been modest. Improved knowledge of the aberrant molecular signaling pathways found in NSCLC has led to the development of biomarkers with associated targeted therapeutics, thus changing the treatment paradigm for many NSCLC patients. In this review, we present a summary of many of the currently investigated biologic targets in NSCLC, discuss their current clinical trial status, and also discuss the potential for development of other targeted agents. PMID:23696960

  5. Interim report on intrathoracic radiotherapy of human small-cell lung carcinoma in nude mice with Re-188-RC-160, a radiolabeled somatostatin analogue

    SciTech Connect

    Zamora, P.O. |; Bender, H.; Biersack, H.J.; Knapp, F.F. Jr.

    1995-07-01

    The purpose of this study was to evaluate the therapeutic efficacy of Re-188-RC-160 in experimental models of human small cell lung carcinomas which mimic the clinical presentation. In the experimental model, cells from the human small cell lung carcinoma cell line NCI-H69 cells were inoculated into the thoracic cavity of athymic mice and rats. Subsequently, the biodistribution of Re-188-RC-160 after injection into the pleural cavity, a radiolabeled somatostatin analogue, was monitored as was the effect on the subsequent growth of tumors. The results presented here, and which are a part of a larger series of studies, suggest that Re-188-RC-160 can be effectively used in this animal model to restrict the growth of small cell lung carcinoma in the thoracic cavity.

  6. Veliparib With or Without Radiation Therapy, Carboplatin, and Paclitaxel in Patients With Stage III Non-small Cell Lung Cancer That Cannot Be Removed by Surgery

    ClinicalTrials.gov

    2016-08-31

    Bronchioloalveolar Carcinoma; Large Cell Lung Carcinoma; Lung Adenocarcinoma; Lung Adenocarcinoma, Mixed Subtype; Squamous Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer

  7. Different effects of the polysaccharide levan on the oncogenicity of cells of two variants of Lewis lung carcinoma.

    PubMed Central

    Stark, Y.; Leibovici, J.

    1986-01-01

    A marked difference in sensitivity to the direct effect of the polysaccharide levan on tumour cells was observed between two variants of malignancy of Lewis lung carcinoma: cells of the more malignant variant (3LL-M) were much more sensitive to the drug than those of the less malignant tumour (3LL). A gradual decrease in tumorigenicity following preincubation with increasing levan concentrations was observed with both variants, but statistically significant inhibition was observed at lower levan concentrations with 3LL-M than with 3LL. PMID:3947532

  8. Mediastinal irradiation in a patient affected by lung carcinoma after heart transplantation: Helical tomotherapy versus three dimensional conformal radiotherapy

    PubMed Central

    Iorio, Vincenzo; Cammarota, Fabrizio; Toledo, Diego; Senese, Rossana; Francomacaro, Ferdinando; Muto, Matteo; Muto, Paolo

    2016-01-01

    Abstract Patients who have undergone solid organ transplants are known to have an increased risk of neoplasia compared with the general population. We report our experience using mediastinal irradiation with helical tomotherapy versus three‐dimensional conformal radiation therapy to treat a patient with lung carcinoma 15 years after heart transplantation. Our dosimetric evaluation showed no particular difference between the techniques, with the exception of some organs. Mediastinal irradiation after heart transplantation is feasible and should be considered after evaluation of the risk. Conformal radiotherapy or intensity‐modulated radiotherapy appears to be the appropriate treatment in heart‐transplanted oncologic patients. PMID:27148425

  9. Mediastinal irradiation in a patient affected by lung carcinoma after heart transplantation: Helical tomotherapy versus three dimensional conformal radiotherapy.

    PubMed

    Giugliano, Francesca M; Iorio, Vincenzo; Cammarota, Fabrizio; Toledo, Diego; Senese, Rossana; Francomacaro, Ferdinando; Muto, Matteo; Muto, Paolo

    2016-04-26

    Patients who have undergone solid organ transplants are known to have an increased risk of neoplasia compared with the general population. We report our experience using mediastinal irradiation with helical tomotherapy versus three-dimensional conformal radiation therapy to treat a patient with lung carcinoma 15 years after heart transplantation. Our dosimetric evaluation showed no particular difference between the techniques, with the exception of some organs. Mediastinal irradiation after heart transplantation is feasible and should be considered after evaluation of the risk. Conformal radiotherapy or intensity-modulated radiotherapy appears to be the appropriate treatment in heart-transplanted oncologic patients. PMID:27148425

  10. Atypical carcinoid and large cell neuroendocrine carcinoma of the lung: a proteomic dataset from formalin-fixed archival samples.

    PubMed

    Tanca, Alessandro; Addis, Maria Filippa; Pisanu, Salvatore; Abbondio, Marcello; Pagnozzi, Daniela; Eccher, Albino; Rindi, Guido; Cossu-Rocca, Paolo; Uzzau, Sergio; Fanciulli, Giuseppe

    2016-06-01

    Here we present a dataset generated using formalin-fixed paraffin-embedded archival samples from two rare lung neuroendocrine tumor subtypes (namely, two atypical carcinoids, ACs, and two large-cell neuroendocrine carcinomas, LCNECs). Samples were subjected to a shotgun proteomics pipeline, comprising full-length protein extraction, SDS removal through spin columns, in solution trypsin digestion, long gradient liquid chromatography peptide separation and LTQ-Orbitrap mass spectrometry analysis. A total of 1260 and 2436 proteins were identified in the AC and LCNEC samples, respectively, with FDR <1%. MS data are available in the PeptideAtlas repository at http://www.peptideatlas.org/PASS/PASS00375. PMID:27054153

  11. Atypical carcinoid and large cell neuroendocrine carcinoma of the lung: a proteomic dataset from formalin-fixed archival samples

    PubMed Central

    Tanca, Alessandro; Addis, Maria Filippa; Pisanu, Salvatore; Abbondio, Marcello; Pagnozzi, Daniela; Eccher, Albino; Rindi, Guido; Cossu-Rocca, Paolo; Uzzau, Sergio; Fanciulli, Giuseppe

    2016-01-01

    Here we present a dataset generated using formalin-fixed paraffin-embedded archival samples from two rare lung neuroendocrine tumor subtypes (namely, two atypical carcinoids, ACs, and two large-cell neuroendocrine carcinomas, LCNECs). Samples were subjected to a shotgun proteomics pipeline, comprising full-length protein extraction, SDS removal through spin columns, in solution trypsin digestion, long gradient liquid chromatography peptide separation and LTQ-Orbitrap mass spectrometry analysis. A total of 1260 and 2436 proteins were identified in the AC and LCNEC samples, respectively, with FDR <1%. MS data are available in the PeptideAtlas repository at http://www.peptideatlas.org/PASS/PASS00375. PMID:27054153

  12. Mapping Bronchial Carcinoma In Situ Lung Cancer Lesions By Combined Imaging Fluorescence Bronchoscopy And Ratioing Fluorometer Probe

    NASA Astrophysics Data System (ADS)

    Balchum, Oscar J.; Profio, A. Edward; Razum, Nickolas J.

    1988-06-01

    A two-component system of instrumentation and methods, IFB and RFP, when used in combination employing hematoporphyrin derivates, DHE, had highly satisfactory sensitivity (95%) and specificity (100%) for localizing carcinoma in situ lesions in the bronchi of individuals with early stage lung cancer, having a normal chest x-ray and detected by a positive sputum cytology test. The more detailed mapping of additional subjects may increase the specificity of RFP (Ratioing Fluorometer Probe) by itself to an adequate level. Digital computer subs traction of background antofluorescence may increase contrast to enhance the specificity of IFB (Imaging Fluorescence Bronchoscopy).

  13. Spontaneous Regression of Hepatocellular Carcinoma with Multiple Lung Metastases: A Case Report and Review of the Literature.

    PubMed

    Pectasides, Eirini; Miksad, Rebecca; Pyatibrat, Sergey; Srivastava, Amogh; Bullock, Andrea

    2016-09-01

    Spontaneous regression of hepatocellular carcinoma (HCC) is a rare event. Here we present a case of spontaneous regression of metastatic HCC. A 53-year-old man with hepatitis C and alcoholic cirrhosis was found to have a large liver mass consistent with HCC based on its radiographic features. Imaging also revealed left portal and hepatic vein thrombosis, as well as multiple lung nodules concerning for metastases. Approximately 2 months after the initial diagnosis, both the primary liver lesion and the lung metastases decreased in size and eventually resolved without any intervention. Thereafter, the left hepatic vein thrombus progressed into the inferior vena cava and the right atrium, and the patient died due to right heart failure. In this case report and literature review, we discuss the potential mechanisms for and review the literature on spontaneous regression of metastatic HCC. PMID:27038447

  14. Integrative Genomic Analyses Identify BRF2 as a Novel Lineage-Specific Oncogene in Lung Squamous Cell Carcinoma

    PubMed Central

    Lockwood, William W.; Chari, Raj; Coe, Bradley P.; Thu, Kelsie L.; Garnis, Cathie; Malloff, Chad A.; Campbell, Jennifer; Williams, Ariane C.; Hwang, Dorothy; Zhu, Chang-Qi; Buys, Timon P. H.; Yee, John; English, John C.; MacAulay, Calum; Tsao, Ming-Sound; Gazdar, Adi F.; Minna, John D.; Lam, Stephen; Lam, Wan L.

    2010-01-01

    Background Traditionally, non-small cell lung cancer is treated as a single disease entity in terms of systemic therapy. Emerging evidence suggests the major subtypes—adenocarcinoma (AC) and squamous cell carcinoma (SqCC)—respond differently to therapy. Identification of the molecular differences between these tumor types will have a significant impact in designing novel therapies that can improve the treatment outcome. Methods and Findings We used an integrative genomics approach, combing high-resolution comparative genomic hybridization and gene expression microarray profiles, to compare AC and SqCC tumors in order to uncover alterations at the DNA level, with corresponding gene transcription changes, which are selected for during development of lung cancer subtypes. Through the analysis of multiple independent cohorts of clinical tumor samples (>330), normal lung tissues and bronchial epithelial cells obtained by bronchial brushing in smokers without lung cancer, we identified the overexpression of BRF2, a gene on Chromosome 8p12, which is specific for development of SqCC of lung. Genetic activation of BRF2, which encodes a RNA polymerase III (Pol III) transcription initiation factor, was found to be associated with increased expression of small nuclear RNAs (snRNAs) that are involved in processes essential for cell growth, such as RNA splicing. Ectopic expression of BRF2 in human bronchial epithelial cells induced a transformed phenotype and demonstrates downstream oncogenic effects, whereas RNA interference (RNAi)-mediated knockdown suppressed growth and colony formation of SqCC cells overexpressing BRF2, but not AC cells. Frequent activation of BRF2 in >35% preinvasive bronchial carcinoma in situ, as well as in dysplastic lesions, provides evidence that BRF2 expression is an early event in cancer development of this cell lineage. Conclusions This is the first study, to our knowledge, to show that the focal amplification of a gene in Chromosome 8p12, plays

  15. Cure Rates in Small Cell and Non-Small Cell Carcinoma of the Lung Utilizing High-Dose Radiotherapy and Chemotherapy

    PubMed Central

    Akbiyik, Nejat; Alexander, Leslie L.

    1986-01-01

    From 1967 to 1977, 72 patients with small cell carcinoma of the lung were seen. Thirty-five of these patients had unilaterally localized lesions (limited disease) and were treated with cobalt 60 radiation therapy (6,000 rad in six weeks) followed by chemotherapy consisting of cyclophosphamide (Cytoxan), vincristine, methotrexate and lomustine (CCNU) (Group A). The remaining 37 patients with extensive disease were treated with similar chemotherapy alone, or in combination with local palliative radiotherapy to the symptomatic area (Group B). For Group A the five-year survival rate was 20 percent, while for both groups combined, it was only 5 percent. During this same period 560 patients with non-small cell carcinomas were treated. The five-year survival rate for those patients with operable, resectable lesions was 33 percent, while for those with unilateral, inoperable, unresectable lesions, it was 10 percent. Thus, it would appear that the results in limited small cell and non-small cell carcinomas of the lung utilizing high-dose radiotherapy followed by chemotherapy are comparable, and that limited small cell carcinoma of the lung patients with high-dose radiotherapy followed by chemotherapy can survive longer than those patients with stage III, non-small cell lung carcinoma. While the two- to five-year survival rates in small cell carcinoma demonstrate no appreciable differences, in non-small cell carcinomas there are significant two- to five-year survival differences. These improved results probably are due to the increased sensitivity of small cell carcinoma to high-dose local radiotherapy and to the chemotherapeutic vulnerability of circulating and microscopic metastatic cancer cells. PMID:3012100

  16. Synthetic Lethal Therapy for KRAS Mutant Non-small-cell Lung Carcinoma with Nanoparticle-mediated CDK4 siRNA Delivery

    PubMed Central

    Mao, Cheng-Qiong; Xiong, Meng-Hua; Liu, Yang; Shen, Song; Du, Xiao-Jiao; Yang, Xian-Zhu; Dou, Shuang; Zhang, Pei-Zhuo; Wang, Jun

    2014-01-01

    The KRAS mutation is present in ~20% of lung cancers and has not yet been effectively targeted for therapy. This mutation is associated with a poor prognosis in non-small-cell lung carcinomas (NSCLCs) and confers resistance to standard anticancer treatment drugs, including epidermal growth factor receptor tyrosine kinase inhibitors. In this study, we exploited a new therapeutic strategy based on the synthetic lethal interaction between cyclin-dependent kinase 4 (CDK4) downregulation and the KRAS mutation to deliver micellar nanoparticles (MNPs) containing small interfering RNA targeting CDK4 (MNPsiCDK4) for treatment in NSCLCs harboring the oncogenic KRAS mutation. Following MNPsiCDK4 administration, CDK4 expression was decreased, accompanied by inhibited cell proliferation, specifically in KRAS mutant NSCLCs. However, this intervention was harmless to normal KRAS wild-type cells, confirming the proposed mechanism of synthetic lethality. Moreover, systemic delivery of MNPsiCDK4 significantly inhibited tumor growth in an A549 NSCLC xenograft murine model, with depressed expression of CDK4 and mutational KRAS status, suggesting the therapeutic promise of MNPsiCDK4 delivery in KRAS mutant NSCLCs via a synthetic lethal interaction between KRAS and CDK4. PMID:24496383

  17. Meta-analysis of incidence of early lung toxicity in 3-dimensional conformal irradiation of breast carcinomas

    PubMed Central

    2013-01-01

    Background This meta-analysis aims to ascertain the significance of early lung toxicity with 3-Dimensional (3D) conformal irradiation for breast carcinomas and identify the sub-groups of patients with increased risk. Methods Electronic databases, reference sections of major oncological textbooks and identified studies were searched for synonyms of breast radiotherapy and radiation pneumonitis (RP). Major studies in thoracic irradiation were reviewed to identify factors frequently associated with RP. Meta-analysis for RP incidence estimation and odds ratio calculation were carried out. Results The overall incidence of Clinical and Radiological RP is 14% and 42% respectively. Ten studies were identified. Dose-volume Histogram (DVH) related dosimetric factors (Volume of lung receiving certain dose, Vdose and Mean lung Dose, MLD), supraclavicular fossa (SCF) irradiation and age are significantly associated with RP, but not sequential chemotherapy and concomitant use of Tamoxifen. A poorly powered study in IMN group contributed to the negative finding. Smoking has a trend towards protective effect against RP. Conclusion Use of other modalities may be considered when Ipsilateral lung V20Gy > 30% or MLD > 15 Gy. Extra caution is needed in SCF and IMN irradiation as they are likely to influence these dosimetric parameters. PMID:24229418

  18. ZFX knockdown inhibits growth and migration of non-small cell lung carcinoma cell line H1299.

    PubMed

    Li, Kui; Zhu, Zhi-Chuan; Liu, Yong-Jie; Liu, Ji-Wei; Wang, Hong-Tao; Xiong, Zhi-Qi; Shen, Xu; Hu, Ze-Lan; Zheng, Jing

    2013-01-01

    ZFX (zinc finger transcription factor, X chromosome-linked) contributes to the maintenance of different types of stem cells and the progression of various cancers. We have previously reported that ZFX knockdown inhibits proliferation of glioma in vitro and in vivo. Since overexpression of ZFX in lung cancer tissue correlates with lymph node metastasis, we hypothesized that ZFX may play a role in lung cancer. In this study, we identified ZFX as a promoter of lung cancer growth and migration in a NSCLC (non-small cell lung carcinoma) cell line H1299. ZFX knockdown caused proliferation inhibition determined by MTT assay and colony formation assay, G0/G1 arrest of cell cycle and slightly increased proportion of apoptotic cells assessed by flow cytometry assay, decreased population of migrating cells showed by wound-healing assay, increased cell senescence evidenced by senescence-associated β-galactosidase staining. ZFX knockdown also led to decreased proportion of tumor bearing mice and reduced mean tumor volume in a subcutaneous tumor model. In addition, western blot showed that ZFX knockdown down regulated a set of proteins involved in proliferation, survival and motility. Altogether, these results suggest that ZFX may be a potential therapeutic target for NSCLC. PMID:24228108

  19. [Relapse-Free Survival Following Multidisciplinary Therapy for Hepatocellular Carcinoma with Multiple Lung Metastases--A Case Report].

    PubMed

    Hasegawa, Hirofumi; Ueda, Shigeru; Nakanoko, Tomonori; Gion, Tomonobu; Kitamura, Masayuki; Tanaka, Fumihiro

    2015-11-01

    Chemotherapy is not effective for metastatic hepatocellular carcinoma(HCC); however, prolonged survival can be expected for patients with multiple metastases who are treated with surgical resection in addition to chemotherapy. We present a case of a 36-year-old woman with hepatitis B who developed HCC with multiple intrahepatic and lung metastases after undergoing resection of HCC in 2010 in Canada. The patient returned to Japan for additional treatment. She was treated with TACE therapy and systemic chemotherapy, but her lung metastases did not improve. The patient's PIVKA-Ⅱ levels remained moderately elevated after initiation of chemotherapy. Therefore, we performed surgical resection of the lung metastases in March 2014. Five months later, the patient received additional TACE therapy when an isolated metastasis was found in the residual liver. Since then, no recurrence of HCC has been found, and the patient's PIVKA-Ⅱ levels have remained in the normal range. This case demonstrates that surgical resection for multiple lung metastases is possible in select patients. PMID:26805204

  20. Synergistic effect of ERK inhibition on tetrandrine-induced apoptosis in A549 human lung carcinoma cells.

    PubMed

    Cho, Hyun Sun; Chang, Seung Hee; Chung, Youn Sun; Shin, Ji Young; Park, Sung Jin; Lee, Eun Sun; Hwang, Soon Kyung; Kwon, Jung Taek; Tehrani, Arash Minai; Woo, Minah; Noh, Mi Sook; Hanifah, Huda; Jin, Hua; Xu, Cheng Xiong; Cho, Myung Haing

    2009-03-01

    Tetrandrine (TET), a bis-benzylisoquinoline alkaloid from the root of Stephania tetrandra, is known to have anti-tumor activity in various malignant neoplasms. However, the precise mechanism by which TET inhibits tumor cell growth remains to be elucidated. The present studies were performed to characterize the potential effects of TET on phosphoinositide 3-kinase/Akt and extracellular signal-regulated kinase (ERK) pathways since these signaling pathways are known to be responsible for cell growth and survival. TET suppressed cell proliferation and induced apoptosis in A549 human lung carcinoma cells. TET treatment resulted in a down-regulation of Akt and ERK phosphorylation in both time-/concentration-dependent manners. The inhibition of ERK using PD98059 synergistically enhanced the TET-induced apoptosis of A549 cells whereas the inhibition of Akt using LY294002 had a less significant effect. Taken together, our results suggest that TET: i) selectively inhibits the proliferation of lung cancer cells by blocking Akt activation and ii) increases apoptosis by inhibiting ERK. The treatment of lung cancers with TET may enhance the efficacy of chemotherapy and radiotherapy and increase the apoptotic potential of lung cancer cells. PMID:19255520

  1. Regression of squamous cell carcinoma of the lung by Chinese herbal medicine: a case with an 8-year follow-up.

    PubMed

    Liang, H L M; Xue, C C L; Li, C G

    2004-03-01

    A 51-year-old woman diagnosed with squamous cell carcinoma (SCC) of the lung (T2N2M0) by cytological tests and a CT scan has survived for 8 years. During this period of time, she had been treated with Chinese herbal medicine alone for 4 years. The herbal prescription consisted of nine Chinese medicinal herbs. These herbs have been reported to possess anti-tumour and immune enhancing effects. Therefore, it is suggested that the herbal treatment for this patient might have contributed to the complete regression of her lung carcinoma. Further research on the actions of these herbs is warranted. PMID:15165095

  2. Endometrial thickness and risk of breast and endometrial carcinomas in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

    PubMed Central

    Felix, Ashley S.; Weissfeld, Joel L.; Pfeiffer, Ruth M.; Modugno, Francesmary; Black, Amanda; Hill, Lyndon M.; Martin, Jerry; Sit, Anita S.; Sherman, Mark E.; Brinton, Louise A.

    2013-01-01

    Postmenopausal women with higher circulating estrogen levels are at increased risk of developing breast and endometrial carcinomas. In the endometrium, excess estrogen relative to progesterone produces a net proliferative stimulus, which may result in endometrial thickening. Therefore, we tested the hypothesis that endometrial thickness is a biological marker of excess estrogen stimulation that is associated with risk of breast and endometrial carcinomas. Endometrial thickness was measured in 1,272 postmenopausal women, aged 55–74, who underwent transvaginal ultrasound (TVU) screening as part of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Serial endometrial thickness measurements were available for a subset of women at one (n=1,018), two (n=869) and three years (n=641) after baseline. We evaluated associations between endometrial thickness and breast (n=91) and endometrial (n=14) carcinoma by estimating relative risks (RRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression with age as the time metric. Models incorporating baseline endometrial thickness and as a time-varying covariate using all measurements were examined. Median follow-up among study participants was 12.5 years (range: 0.3–13.8 years). Compared to baseline endometrial thickness of 1.0 – 2.99 mm, women with baseline endometrial thickness greater than or equal to 5.0 mm had an increased risk of breast (RR: 2.00, 95% CI 1.15, 3.48) and endometrial (RR: 5.02, 95% CI 0.96, 26.36) carcinomas in models adjusted for menopausal hormone use and BMI. Our data suggest that increased endometrial thickness as assessed by TVU was associated with increased risk of breast and endometrial carcinomas. PMID:23907658

  3. How today's developments in the treatment of non-small cell lung cancer will change tomorrow's standards of care.

    PubMed

    Kris, Mark G

    2005-10-01

    Cisplatin (Platinol; Bristol-Myers Squibb, Princeton, NJ, http://www.bms.com) and carboplatin (Paraplatin; Bristol-Myers Squibb), together with newer chemotherapies, such as docetaxel (Taxotere; Aventis Pharmaceuticals Inc., Bridgewater, NJ, http://www.aventispharma-us.com), paclitaxel (Taxol; Bristol-Myers Squibb), vinorelbine (Navelbine; GlaxoSmith-Kline, Philadelphia, http://www.gsk.com), pemetrexed (Alimta; Eli Lilly and Company, Indianapolis, http://www.lilly.com), and gemcitabine (Gemzar; Eli Lilly and Company), have improved treatment outcomes in both advanced non-small cell lung cancer (NSCLC) and in the adjuvant/neoadjuvant setting. Newer systemic treatments for NSCLC, used in advanced stage IV management, are beginning to be studied in earlier stages of the disease, when treatment is better tolerated and potentially curative. Hopefully, newer agents with proven efficacies in advanced disease will enhance curability. Following the successful addition of bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA, http://www.gene.com) to carboplatin/paclitaxel in advanced disease, bevacizumab is now being incorporated into adjuvant and neoadjuvant trials. Trials in stage IB-IIIA patients will study neoadjuvant docetaxel/cisplatin/bevacizumab. The discovery that patients with exon 19 and 21 mutations in the epidermal growth factor receptor gene EGFR have around an 80% response rate to gefitinib (Iressa; AstraZeneca Pharmaceuticals, Wilmington, DE, http:// www.astrazeneca-us.com) and that this response confers survival benefit indicates its potential utility for mutation-positive patients with advanced- and earlier-stage disease. Clinical characteristics, such as never smoking status and adenocarcinoma, and especially bronchioloalveolar carcinoma histological features, can also identify individuals likely to respond to EGFR tyrosine kinase inhibitors. Studies of neoadjuvant erlotinib (Tarceva; OSI Pharmaceuticals, Inc., Melville, NY, http

  4. Increased expression of the Th17-IL-6R/pSTAT3/BATF/RorγT-axis in the tumoural region of adenocarcinoma as compared to squamous cell carcinoma of the lung.

    PubMed

    Balabko, Ljubov; Andreev, Katerina; Burmann, Nadine; Schubert, Melanie; Mathews, Martina; Trufa, Denis I; Reppert, Sarah; Rau, Tilmann; Schicht, Martin; Sirbu, Horia; Hartmann, Arndt; Finotto, Susetta

    2014-01-01

    Here we describe increased expression of IL6R in the tumoural region of lung tissue from patients affected by lung adenocarcinoma as compared to squamous cell lung carcinoma. Moreover, here we found increased IL6R in the tumour free part of the lung. By using a murine model of lung adenocarcinoma, we discovered that few lung tumour cells expressed IL-6R and CD4+CD25+Foxp-3+ T regulatory cells down-regulated IL-6R in the tumour bearing lungs. Downstream of IL-6R, the Th17 lineage-specification factors: Signal transducer and activator of transcription 3 (STAT3), Basic leucine zipper transcription factor, BATF and a protein encoded by the RORC in human (RAR-related orphan receptor C) (RORγT), were also found induced in the tumoural region of lung tissue from patients affected by lung adenocarcinoma as compared to those carrying squamous cell carcinoma. Moreover, pSTAT3 protein was found phosphorylated and auto-phosphorylated in the tumoural region of patients with adeno cell carcinoma of the lung as compared to the tumoural region of patients with squamous cell carcinoma of the lung. Intranasal application of anti-IL-6R antibodies in a murine model of lung adenocarcinoma, induced T regulatory cell markers such as Foxp3, Ctla4, Icos, Il10, Il21, Folr4 and Lag3 and inhibited Rorc in lung adenocarcinoma. PMID:25491772

  5. Advantages of Combined PET-CT in Mediastinal Staging in Patients with Non-small Cell Lung Carcinoma

    PubMed Central

    Beslic, Nermina; Sadija, Amera; Milardovic, Renata; Ceric, Timur; Ceric, Sejla; Beganovic, Adnan; Kristic, Spomenka; Cavaljuga, Semra

    2016-01-01

    Introduction: Precise mediastinal lymph node staging in patients with non-small cell lung carcinoma (NSCLC) provides important prognostic information and it is obligatory in treatment strategy planning. 18Fluoro-deoxy-glucose (18F-FDG) positron emission tomography - computerized tomography (PET-CT) based on detection of metabolic activity showed superiority in preoperative staging of lung carcinoma. Materials and Methods: Total number of 26 patients diagnosed with NSCLC were included in this retrospective, cross-sectional study. Status of mediastinal lymph nodes was assessed in all patients comparing contrast enhanced CT and 18F-FDG PET-CT findings. Discussion: We found in our study that 50% of patients had different N stage on contrast enhanced CT comparing to 18F-FDG PET-CT findings. Among the total number of patients which had different nodal status on PET-CT comparing to CT alone, we found in our study that 54% of patients had change in further therapy protocol after PET-CT change of nodal stage. Conclusion: Combined PET-CT which offers advantages of both modalities is excellent method for nodal (N) staging, so it is recommended in initial staging in patients with NSCLC. PET-CT used preopratively for mediastinal nodal staging has significant impact on further therapy planning and also has an consequential impact on health system savings. PMID:27147799

  6. The Robustness of Pathway Analysis in Identifying Potential Drug Targets in Non-Small Cell Lung Carcinoma

    PubMed Central

    Dalby, Andrew; Bailey, Ian

    2014-01-01

    The identification of genes responsible for causing cancers from gene expression data has had varied success. Often the genes identified depend on the methods used for detecting expression patterns, or on the ways that the data had been normalized and filtered. The use of gene set enrichment analysis is one way to introduce biological information in order to improve the detection of differentially expressed genes and pathways. In this paper we show that the use of network models while still subject to the problems of normalization is a more robust method for detecting pathways that are differentially overrepresented in lung cancer data. Such differences may provide opportunities for novel therapeutics. In addition, we present evidence that non-small cell lung carcinoma is not a series of homogeneous diseases; rather that there is a heterogeny within the genotype which defies phenotype classification. This diversity helps to explain the lack of progress in developing therapies against non-small cell carcinoma and suggests that drug development may consider multiple pathways as treatment targets.

  7. Silibinin reverses drug resistance in human small-cell lung carcinoma cells

    PubMed Central

    Sadava, David; Kane, Susan E.

    2014-01-01

    Small-cell lung carcinoma (SCLC) has a dismal prognosis in part because of multidrug resistance (MDR). Silibinin is a flavonolignan extracted from milk thistle (Silybum marianum), extracts of which are used in traditional medicine. We tested the effects of silibinin on drug-sensitive (H69) and multi-drug resistant (VPA17) SCLC cells. VPA17 cells did not show resistance to silibinin (IC50 = 60µM for H69 and VPA17). Flow cytometry analysis after incubation in 30 µM silibinin showed no changes in cell cycle phases in VPA17 or H69 cells compared with untreated cells. Silibinin (30 µM) incubation was pro-apoptotic in VPA17 cells after >3 days, as measured by ELISA of BUdR labeled DNA fragments. Apoptosis was also indicated by an increase in caspase-3 specific activity and decrease in survivin in VPA17 MDR cells. VPA17 cells had increased Pgp -mediated efflux of calcein acetoxymethyl ester (calcein AM); however, this was inhibited in cells pre-incubated in silibinin for 5 days. Pre-incubation of VPA17 cells in 30 µM silibinin for 5 days also reversed resistance to etoposide (IC50 = 5.50 uM to 0.65 µM) and doxorubicin (IC50 = 0.620 µM to 0.035 µM). The possible synergistic relationship between silibinin and chemotherapy drugs was determined by exposure of VPA17 cells to 1:1 ratios of their respective IC50 values, with serial dilutions at 0.25–2.0 × IC50 and calculation of the combination index (CI). Silibinin and etoposide showed synergism (CI = 0.46 at ED50), as did silibinin and doxorubicin (CI = 0.24 at ED50). These data indicate that in SCLC, silibinin is pro-apoptotic, reverses MDR and acts synergistically with chemotherapy drugs. Silibinin, a non-toxic natural product may be useful in the treatment of drug-resistant SCLC. PMID:23879966

  8. Frequent loss of the expression of multiple subunits of the SWI/SNF complex in large cell carcinoma and pleomorphic carcinoma of the lung.

    PubMed

    Yoshimoto, Taichiro; Matsubara, Daisuke; Nakano, Tomoyuki; Tamura, Tomoko; Endo, Shunsuke; Sugiyama, Yukihiko; Niki, Toshiro

    2015-11-01

    The switch/sucrose non-fermenting (SWI/SNF) complex has recently emerged as a novel tumor suppressor in various human cancers. In the present study, we analyzed the expression of multiple SWI/SNF subunits in primary non-small cell lung cancer (NSCLC). A total of 133 NSCLC, consisting of 25 squamous cell carcinomas (SCC), 70 adenocarcinomas (AD), 16 large cell carcinomas (LC), and 22 pleomorphic carcinomas (PL), were immunohistochemically examined for the expression of BRG1, BRM, BAF47, ARID1A, and ARID1B. The frequency at which reductions in the expression of BRG1 were observed was significantly higher in the LC-PL group (13/38, 34.2%) than in the SCC-AD group (7/95, 7.4%). Similarly, the frequency at which reductions in the expression of BRM were observed was significantly higher in the LC-PL group (17/38, 44.7%) than in the SCC-AD group (14/95, 14.7%). The loss of the expression of ARID1A, ARID1B, and BAF47 was observed only in a fraction of NSCLC cases. Furthermore, the frequency at which the concurrent loss of multiple subunits of the SWI/SNF complex was observed was significantly higher in the LC-PL group (10/38, 26.3%) than in the SCC-AD group (8/95, 8.4%). Collectively, these results indicate that the loss of the SWI/SNF complex was related to dedifferentiation in NSCLC. PMID:26345631

  9. The omega-hydroxy palmitic acid induced apoptosis in human lung carcinoma cell lines H596 and A549.

    PubMed

    Abe, Akihisa; Yamane, Mototeru; Yamada, Hiroyuki; Sugawara, Isamu

    2002-02-01

    We have found that omega-hydroxy palmitic acid (16-hydroxy palmitic acid, omega-HPA) has both cell growth inhibiting and cell death inducing actions on human lung adenosquamous carcinoma cell line H596 and adenocarcinoma cell line A549. Further, these effects were dose- and time-dependent in both cell lines. However, in squamous carcinoma cell line H226, omega-HPA had no cytotoxic effect. On the other hand, in the human small cell lung carcinoma (SCLC) cell line H128, this compound showed weak cytotoxicity. The sensitivity toward omega-HPA was higher in H596 cells than in A549 cells. In both H596 and A549 cells, cell growth was inhibited to 24.4 and 9.4%, respectively, by treatment with 100 microM omega-HPA for 12 h. In the 24 h treatment cells, growth inhibition was increased to 100 and 38.1%, respectively. In cytotoxicity experiments, the number of dead cells increased with incubation times in the presence of omega-HPA: on three days incubation with 100 microM omega-HPA, viability was 0 and 13.5%, respectively, in H596 and A549 cells. Further, the fragmentation of DNA to oligonucleosomal-sized ladder fragments, which is an index of apoptosis, was observed in both cell lines on treatment with omega-HPA. Therefore, it is assumed that these cell deaths induced by omega-HPA, were apoptosis in these cell lines. Since the number of dead cells following treatment with omega-HPA decreased by treatment with omega-HPA in combination with Z-VAD-fmk, a caspase family inhibitor, it is thought that apoptotic cell death was related to caspase activity. PMID:12186781

  10. Analysis of the expression protein profiles of lung squamous carcinoma cell using shot-gun proteomics strategy.

    PubMed

    Nan, Yandong; Yang, Shuanying; Tian, Yingxuan; Zhang, Wei; Zhou, Bin; Bu, Lina; Huo, Shufen

    2009-01-01

    The aim of this study is to globally screen and identify the expression protein profiles of lung squamous carcinoma cell (SqCC) using shot-gun proteomics strategy and to further analyze function of individual proteins by bioinformatics, which may likely result in the identification of new biomarkers and provide helpful clues for pathogenesis, early diagnosis, and progression of lung SqCC. The specific tumor cells were isolated and collected from the tissues of six patients with lung SqCC by laser capture microdissection (LCM). Total proteins from the LCM cells were extracted, digested with trypsin. The sequence information of resulting peptides was acquired by high-performance liquid chromatography (HPLC) and tandem mass spectrometry (TMS). The global protein profiles of lung SqCC cell were identified with BioworksTM software in IPI human protein database. Cellular component, molecular function, and biological process of the all proteins were analyzed using gene ontology (GO). About 720,000 tumor cells were satisfactorily collected from tissues of six patients with lung SqCC by LCM and the homogeneities of cell population were estimated to be over 95% as determined by microscopic visualization. The high resolution profiles including HPLC, full mass spectrum, and tandem mass spectrum were successfully obtained. Database searching of the resulting bimolecular sequence information identified 1982 proteins in all samples. The bioinformatics of these proteins, including amino acids sequence, fraction of coverage, molecular weight, isoelectric point, etc., were analyzed in detail. Among them, the function of most proteins was recognized by using GO. Five candidate proteins, Prohibitin (PHB), Mitogen-activated protein kinase (MAPK), Heat shock protein27 (HSP27), Annexin A1(ANXA1), and High mobility group protein B1 (HMGB1), might play an important role in SqCC genesis, progression, recurrence, and metastasis according to relative literatures. We have successfully isolated

  11. Sorafenib and a novel immune therapy in lung metastasis from hepatocellular carcinoma following hepatectomy: A case report

    PubMed Central

    Yi, Yongxiang; Han, Jianbo; Fang, Yuan; Liu, Dongxiao; Wu, Zuoyou; Wang, Lili; Zhao, Liang; Wei, Qiang

    2016-01-01

    Sorafenib is the standard therapeutic strategy for recurrent hepatocellular carcinoma (HCC) following hepatectomy. However, only few patients truly benefit from this therapy. Thus, new strategies combined with sorafenib are urgently required. We herein present the case of a patient with hepatic and extrahepatic HCC recurrence following hepatectomy, who was treated by combined sorafenib, focused ultrasound knife and DRibbles-pulsed dendritic cell (DC) vaccine. Enzyme-Linked ImmunoSpot assay (ELISPOT) and intracellular staining (ICS) analysis were used to detect the secretion of interferon (IFN)-γ by T cells at different timepoints of the vaccine in order to evaluate the patient's specific T-cell response to SMMC-7721-derived DRibbles vaccine. The α-fetoprotein level decreased from 103,295 to 5 ng/ml and the patient displayed improved liver function, an Eastern Cooperative Oncology Group performance status score of 0, remission of liver metastases and disappearance of the lung metastases 8 months post-combination therapy. The computed tomography scan revealed the disappearance of liver metastases 2 years post-combination therapy. The ELISPOT data revealed a low antigen-specific T-cell response 4 weeks after the first vaccine cycle and the response decreased to nearly zero prior to the second cycle. However, high antigen-specific T-cell response was observed 2 weeks after the second vaccine cycle and did not decrease, even after 10 months, which was consistent with the result of the ICS analysis, which demonstrated that most of the secreted IFN-γ was produced by CD4+ T cells, whereas a low CD8+ T-cell response was observed (0.429 vs. 0.0665%, respectively). Our results demonstrated that antigen-specific T-cell response aimed to treat recurrent HCC may be induced through stimulation by the DC-DRibbles vaccine. The success of the treatment supports the combination of sorafenib, focused ultrasound knife and DC-DRibbles vaccine as a therapeutic strategy for patients

  12. Effects of sorafenib on lung metastasis in rats with hepatocellular carcinoma: the role of microRNAs.

    PubMed

    Shi, Yi; Huang, Aimin

    2015-11-01

    Many patients with advanced hepatocellular carcinoma (HCC) develop lung metastasis and available treatments are limited. The anticancer drug sorafenib has opened a window of hope for patients with advanced hepatocellular carcinoma. However, the effect of sorafenib is limited by drug resistance. MicroRNAs have been reported to play an important role in HCC, but the effect of sorafenib on microRNAs (miRNAs) and on lung metastasis is not clear. This report employed a high-throughput deep sequencing technique to detect the difference of miRNAs and immunohistochemical technique to detect the difference of protein in implanted primary tumors and in metastatic HCC tumors after treatment with sorafenib. Among the detected miRNAs, we identified rno-miR-122-3p and rmo-miR-122-5p that were downregulated and rno-miR-383-5p and rno-miR-34a-5p that were upregulated and one novel miRNAs is reported as downregulated here for the first time. Immunohistochemical analysis of known miRNAs identified CMYC protein expression as inhibited, MDM2 protein was expressed, and NM23 and GST protein were upregulated. A Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of novel miRNA found that the targeted genes were concentrated in pathways of metabolism, especially in cytochrome P450. These results indicate that these miRNAs are likely to be involved in the treatment response of lung metastases of HCC to sorafenib. They may be useful as biomarkers to predict the clinical treatment response of sorafenib. PMID:26026584

  13. Nitric oxide synthase, cyclooxygenase 2, and vascular endothelial growth factor in the angiogenesis of non-small cell lung carcinoma.

    PubMed

    Marrogi, A J; Travis, W D; Welsh, J A; Khan, M A; Rahim, H; Tazelaar, H; Pairolero, P; Trastek, V; Jett, J; Caporaso, N E; Liotta, L A; Harris, C C

    2000-12-01

    We have investigated the hypothesis that nitric oxide synthase (NOS2), cyclooxygenase-2 (COX2), and vascular endothelial growth factor (VEGF) protein levels individually demonstrate a direct correlation with microvessel density (MVD) and clinical outcome in human non-small cell lung cancer (NSCLC). Furthermore, we hypothesized that MVD may explain the propensity of certain histological lung cancer subtypes for early metastasis via a hematological route. Immunohistochemically, we studied the protein expression levels of NOS2, COX2, and VEGF and MVD by counting CD31-reactive blood vessels (BVs) in 106 surgically resected NSCLC specimens. NOS2, COX2, and VEGF immunoreactivity were observed in 48, 48, and 58%, respectively, of the study subjects, and their levels correlated with MVD at the tumor-stromal interphase (P < or = 0.001). More adenocarcindmas and large cell carcinomas displayed overexpression of NOS2 when compared with squamous cell carcinoma (SCC; r = 0.44; P < 0.001). NOS2 and COX2 levels were found to correlate positively with VEGF status (r = 0.44; P < 0.001, 0.01, and 0.03, respectively). These results attest to the significant interaction of these factors in the angiogenesis of NSCLC. Although neither angiogenic factors nor MVD correlated with patient survival, the latter correlated with tumor clinical stage in both squamous (SCC; 73 BVs/mm2) and non-SCC (78 BVs/mm2) tumors. These results indicate that angiogenesis is a complex process that involves multiple factors including NOS2, COX2, and VEGF. Furthermore, the role of angiogenesis in the biology of various histological lung cancer types may be different. The complexity of angiogenesis may explain the modest results observed in antiangiogenesis therapy that target a single protein. PMID:11156228

  14. Monitoring drug induced apoptosis and treatment sensitivity in non-small cell lung carcinoma using dielectrophoresis.

    PubMed

    Taruvai Kalyana Kumar, Rajeshwari; Liu, Shanshan; Minna, John D; Prasad, Shalini

    2016-09-01

    Non-invasive real time methods for characterizing biomolecular events that contribute towards apoptotic kinetics would be of significant importance in the field of cancer biology. Effective drug-induced apoptosis is an important factor for establishing the relationship between cancer genetics and treatment sensitivity. The objective of this study was to develop a non-invasive technique to characterize cancer cells that are undergoing drug-induced apoptosis. We used dielectrophoresis to determine apoptotic cells as early as 2h post drug treatment as compared to 24h with standard flow cytometry method using non-small cell lung cancer (NSCLC) adenocarcinoma cell line (HCC1833) as a study model. Our studies have shown significant differences in apoptotic cells by chromatin condensation, formation of apoptotic bodies and exposure of phosphatidylserine (PS) on the extracellular surface when the cells where treated with a potent Bcl-2 family inhibitor drug (ABT-263). Time lapse dielectrophoretic studies were performed over 24h period after exposure to ABT-263 at clinically relevant concentrations. The dielectrophoretic studies were compared to Annexin-V FITC flow assay for the detection of PS in mid-stage apoptosis using flow cytometry. As a result of physical and biochemical changes, inherent dielectric properties of cells undergoing varying stages of apoptosis showed amplified changes in their cytoplasmic and membrane capacitance. In addition, zeta potential of these fixed isolated cells was measured to obtain direct correlation to biomolecular events. PMID:27262539

  15. Results of resection in non-oat cell carcinoma of the lung with mediastinal lymph node metastases.

    PubMed Central

    Martini, N; Flehinger, B J; Zaman, M B; Beattie, E J

    1983-01-01

    From 1974 to 1981, 1598 patients with non-oat cell carcinoma of the lung were seen and treated. All were staged according to the AJC staging system. Of these, 706 patients had evidence of mediastinal lymph node metastases (N2). There were 151 patients (21%) who had complete, potentially curative resection of their primary tumor and all accessible mediastinal lymph nodes. The histologic type of tumor was adenocarcinoma in 94 patients, epidermoid carcinoma in 46 patients, and large-cell carcinoma in 11 patients. The extent of pulmonary resection consisted of a lobectomy in 119 patients, pneumonectomy in 26 patients, and wedge resection or segmentectomy in six patients. Almost all patients also received radiation therapy to the mediastinum. Clinical staging of the primary tumor and the mediastinum was based on the radiographic presentation of the chest and on bronchoscopy. Before treatment, 104 of 151 patients (69%) were believed to have had stage I (90 patients) or II (14 patients) disease, and 47 patients had stage III disease, of whom only 33 had evidence of mediastinal lymph node involvement. Excluding deaths from unrelated causes, the overall survival rate was 74% at 1 year, 43% at 3 years and 29% at 5 years. Survival in patients with clinical stage I or II disease treated by resection was favorable despite the presence of N2 nodes (50% at 3 years). Survival in obvious clinical N2 disease was poor (8% at 3 years). There was no difference in survival between patients with adenocarcinoma and those with epidermoid carcinoma. However, survival was poorer in patients with N2 nodes in the inferior mediastinum compared to those without lymph node involvement at that level. PMID:6615059

  16. Effects of Lewis lung carcinoma on trabecular microstructural changes in wild-type and plasminogen activator inhibitor-1 deficient mice fed a high-fat diet

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bone is a major target organ of metastasis. The present study investigated the effects of Lewis lung carcinoma (LLC) on trabecular microstructural changes, using tomographic analysis, in distal femur and lumbar 4 vertebra from LLC-bearing wild-type and plasminogen activator inhibitor-1 (PAI-1) defi...

  17. Hypokalaemia as the only clinical symptom of ACTH ectopic secretion in a case of small cell carcinoma of the lung with very rapid evolution.

    PubMed

    Pentimone, F; Donadio, C; Camici, M; Cini, G

    1980-01-01

    A patient with heavy hypokalaemia is described: hypokalaemia and its effects were the unique clinical manifestations of small cell carcinoma of the lung, associated with ACTH ectopic secretion. The rapid unfavourable evolution denotes the explosive behaviour of the syndrome. PMID:7394347

  18. Restricted feeding of a high-fat diet reduces spontaneous metastases of Lewis lung carcinoma in C57BL/6 mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Obesity is a risk factor for cancer. We previously reported that consumption of a high-fat diet enhances metastasis in mice (Yan, Clin Exp Metastasis 2010). The present study investigated the effects of restricted feeding of a high-fat diet on spontaneous metastasis of Lewis lung carcinoma (LLC) i...

  19. One year survival rate in patients with carcinoma of the lung treated with split course irradiation: correlation with serum value of carcinoembryonic antigen. [Linear accelerator

    SciTech Connect

    Bolla, M.; Vrousos, C.; Agnus-Delord, C.; Kolodie, H.; Paramelle, B.

    1980-08-01

    Carcinoembryonic antigen (CEA) radio immune assay was performed in 51 patients with lung carcinoma before and at various times after loco-regional radiotherapy. Increase of CEA level correlated with metastasis or progression of the disease; decrease in CEA levels reflected significant regression or stabilization of the disease.

  20. Consumption of a high-fat diet abrogates inhibitory effects of methylseleninic acid on spontaneous metastasis of Lewis lung carcinoma in mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We investigated the effect of dietary supplementation with selenium (Se) on spontaneous metastasis of Lewis lung carcinoma (LLC) in male C57BL/6 mice fed a high-fat diet. Mice were fed the AIN93G diet or that diet modified with 45% calories from fat supplemented with or without 2.5 mg Se/4029 kCal ...

  1. Effects of a high-fat diet on spontaneous metastasis of Lewis lung carcinoma in plasminogen activator inhibitor-1 deficient and wild-type mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We investigated the effects of plasminogen activator inhibitor-1 (PAI-1) deficiency on spontaneous metastasis of Lewis lung carcinoma (LLC) in PAI-1 deficient (PAI-1-/-) and wildtype mice (C57BL/6J background) fed the AIN93G diet or that diet modified with 45% calories from fat. The high-fat diet i...

  2. Urachal Carcinoma with Choroidal, Lung, Lymph Node, Adrenal, Mammary, and Bone Metastases and Peritoneal Carcinomatosis Showing Partial Response after Chemotherapy Treatment with a Modified Docetaxel, Cisplatin and 5-Fluorouracil Regimen

    PubMed Central

    Dekeister, Kathleen; Viguier, Jean Louis; Martin, Xavier; Nguyen, Anh Minh; Boyle, Helen; Flechon, Aude

    2016-01-01

    Urachal carcinoma (UC) is a rare tumor mainly affecting middle-aged males. Metastases occur most frequently in lymph nodes and the lungs. There are no standard adjuvant and metastatic treatments. We report the case of a 36-year-old female with UC treated with partial cystectomy who relapsed 3 years after surgery with left choroidal, lung, mediastinal lymph node, right adrenal, mammary, and bone metastases as well as peritoneal carcinomatosis. She obtained a partial response after 10 cycles of chemotherapy with a modified docetaxel, cisplatin and 5-fluorouracil (mTPF) regimen. This is the first report on the use of the mTPF regimen in UC and on the existence of choroidal, adrenal, and mammary metastases. PMID:27194981

  3. Extensive disease small cell carcinoma of the lung; trial of non-cross resistant chemotherapy and consolidation radiotherapy. [X ray

    SciTech Connect

    Dillman, R.O., Taelle, R., Segren, S.; Royston, I.; Koziol, J.; Mendelsohn, J.

    1982-05-15

    Twenty-nine patients with extensive disease, small-cell carcinoma of the lung, were treated with two cycles of intensive combination chemotherapy: HexaVAC (hexamethylmelamine, vincristine, Adriamycin, cyclophosphamide). Responders received prophylactic cranial radiation (2000 rad/10 fractions) and non cross resistant chemotherapy via a schedule of alternating cycles of CMV (cyclophosphamide, methotrexate, VP-16-213) and AMV (Adriamycin, methotrexate, VP-16-213). Whenever a complete response was achieved, consolidation radiotherapy was given to the lung primary (4000 rad/20 fractions, split dose) and abdominal metastases (2000 rad/10 fractions) synchronous with CMV therapy. The complete response rate was 14% with HexaVAC, but increased to 38% during CMV/AMV. Total response rate (complete and partial) was 59% and median survival was 42 weeks. Prophylactic brain radiation prevented clinical relapse in the brain in all 14 patients who received it. However, consolidation radiotherapy failed to prevent clinical relapse in the lung and/or liver, and therapeutic brain radiation (3000 rad) failed to prevent relapse in that site. The simultaneous administration of radiotherapy and chemotherapy was well-tolerated although two patients with poor performance status died of infectious complications while leukopenic. In spite of the high response rate, durable remissions with prolonged disease free survival were rare. Further evaluation of induction, consolidation, and maintenance modes of therapy are indicated.

  4. Adoptive immunotherapy using T lymphocytes redirected to glypican-3 for the treatment of lung squamous cell carcinoma

    PubMed Central

    Li, Kesang; Pan, Xiaorong; Bi, Yanyu; Xu, Wen; Chen, Cheng; Gao, Huiping; Shi, Bizhi; Jiang, Hua; Yang, Shengli; Jiang, Liyan; Li, Zonghai

    2016-01-01

    There are unmet medical needs for patients with lung squamous cell carcinoma (LSCC). Therefore, in this study, we explored the antitumor potential of third-generation glypican 3 (GPC3)-redirected chimeric antigen receptor (CAR)-engineered T lymphocytes (CARgpc3 T cells) in tumor models of LSCC. First, we demonstrated by immunohistochemistry (IHC) that GPC3 was expressed in 66.3% of LSCC samples and in 3.3% of lung adenocarcinoma (LAD) samples but not in normal lung tissues. In the presence of GPC3-positive LSCC cells, CARgpc3 T cells were highly activated and increased in number. CARgpc3 T cells could specifically lyse GPC3-positive LSCC cells in vitro. In two established LSCC xenograft models, CARgpc3 T cells could almost completely eliminate the growth of GPC3-positive cells. Additionally, the CARgpc3 T cells were able to persist in vivo and efficiently infiltrate the cancerous tissues. Taken together, these findings indicate that CARgpc3 T cells might be a novel potential therapeutic agent for the treatment of patients with LSCC. PMID:26684028

  5. Reactivation of MASPIN in non-small cell lung carcinoma (NSCLC) cells by artificial transcription factors (ATFs)

    PubMed Central

    Beltran, Adriana S

    2011-01-01

    Tumor suppressor genes have antiproliferative and antimetastatic functions and thus, they negatively affect tumor progression. Reactivating specific tumor suppressor genes would offer an important therapeutic strategy to block tumor progression. Mammary serine protease inhibitor (MASPIN) is a tumor suppressor gene that is not mutated or rearranged in tumor cells, but is silenced during metastatic progression by transcriptional and epigenetic mechanisms. In this work, we have investigated the ability of artificial transcription factors (ATFs) to reactivate MASPIN expression and to reduce tumor growth and metastatic dissemination in non-small cell lung carcinoma (NSCLC) cell lines carrying a hypermethylated MASPIN promoter. We found that the ATFs linked to transactivator domains were able to demethylate the MASPIN promoter. Consistently, we observed that co-treatment of ATF-transduced cells with methyltransferase inhibitors enhanced MASPIN expression as well as induction of tumor cell apoptosis. In addition to tumor suppressive functions, restoration of endogenous MASPIN expression was accompanied by inhibition of metastatic dissemination in nude mice. ATF-mediated reactivation of MASPIN lead to changes in cell motility and to induction of E-CADHERIN. These data suggest that ATFs are able to reprogram aggressive lung tumor cells towards a more epithelial, differentiated phenotype and represent novel therapeutic agents for metastatic lung cancers. PMID:20948306

  6. Expression of a disintegrin and metalloprotease (ADAM and ADAMTS) enzymes in human non-small-cell lung carcinomas (NSCLC)

    PubMed Central

    Rocks, N; Paulissen, G; Quesada Calvo, F; Polette, M; Gueders, M; Munaut, C; Foidart, J-M; Noel, A; Birembaut, P; Cataldo, D

    2006-01-01

    A Disintegrin and Metalloprotease (ADAM) are transmembrane proteases displaying multiple functions. ADAM with ThromboSpondin-like motifs (ADAMTS) are secreted proteases characterised by thrombospondin (TS) motifs in their C-terminal domain. The aim of this work was to evaluate the expression pattern of ADAMs and ADAMTS in non small cell lung carcinomas (NSCLC) and to investigate the possible correlation between their expression and cancer progression. Reverse transcriptase–polymerase chain reaction (RT–PCR), Western blot and immunohistochemical analyses were performed on NSCLC samples and corresponding nondiseased tissue fragments. Among the ADAMs evaluated (ADAM-8, -9, -10, -12, -15, -17, ADAMTS-1, TS-2 and TS-12), a modulation of ADAM-12 and ADAMTS-1 mRNA expression was observed. Amounts of ADAM-12 mRNA transcripts were increased in tumour tissues as compared to the corresponding controls. In sharp contrast, ADAMTS-1 mRNA levels were significantly lower in tumour tissues when compared to corresponding nondiseased lung. These results were corroborated at the protein level by Western blot and immunohistochemistry. A positive correlation was observed between the mRNA levels of ADAM-12 and those of two vascular endothelial growth factor (VEGF)-A isoforms (VEGF-A165 and VEGF-A121). Taken together, these results providing evidence for an overexpression of ADAM-12 and a lower expression of ADAMTS-1 in non-small-cell lung cancer suggest that these proteases play different functions in cancer progression. PMID:16495931

  7. LOSS OF P130 ACCELERATES TUMOR DEVELOPMENT IN A MOUSE MODEL FOR HUMAN SMALL CELL LUNG CARCINOMA

    PubMed Central

    Schaffer, Bethany E.; Park, Kwon-Sik; Yiu, Gloria; Conklin, Jamie F.; Lin, Chenwei; Burkhart, Deborah L.; Karnezis, Anthony N.; Sweet-Cordero, Alejandro; Sage, Julien

    2010-01-01

    Small cell lung carcinoma (SCLC) is a neuroendocrine subtype of lung cancer. While SCLC patients often initially respond to therapy, tumors nearly always recur, resulting in a 5-year survival rate of less than 10%. A mouse model has been developed based on the fact that the RB and p53 tumor suppressor genes are mutated in more than 90% of human SCLCs. Emerging evidence in patients and mouse models suggests that p130, a gene related to RB, may act as a tumor suppressor in SCLC cells. To test this idea, we used conditional mutant mice to delete p130 in combination with Rb and p53 in adult lung epithelial cells. We found that loss of p130 resulted in increased proliferation and significant acceleration of SCLC development in this triple knockout mouse model. The histopathological features of the triple mutant mouse tumors closely resembled that of human SCLC. Genome-wide expression profiling experiments further showed that Rb/p53/p130 mutant mouse tumors were similar to human SCLC. These findings indicate that p130 plays a key tumor suppressor role in SCLC. Rb/p53/p130 mutant mice provide a novel pre-clinical mouse model to identify novel therapeutic targets against SCLC. PMID:20406986

  8. EBUS-guided mediastinal lung cancer staging: monitoring of quality standards improves performance.

    PubMed

    Evison, Matthew; Crosbie, Philip; Martin, Julie; Shah, Rajesh; Doran, Helen; Borrill, Zoe; Hoyle, Jennifer; Rana, Durgesh; Bailey, Simon; Booton, Richard

    2016-08-01

    This audit examined key performance indices related to endobronchial ultrasound (EBUS)-guided mediastinal lung cancer staging before and after the introduction of defined quality standards, at four independent EBUS centres in one cancer network. Data from 642 procedures were prospectively collected and analysed. The introduction of standards was associated with a significant increase (p<0.001) in sampling of key mediastinal lymph node stations (4R, 4L and 7) and a reduction in the variability of staging sensitivity between centres. These data reinforce the requirement for an appropriate regulatory framework for EBUS-transbronchial needle aspiration provision that includes quality assurance and performance monitoring. PMID:27146201

  9. Antitumor and antiproliferative effects of an aqueous extract from the marine diatom Haslea ostrearia (Simonsen) against solid tumors: lung carcinoma (NSCLC-N6), kidney carcinoma (E39) and melanoma (M96) cell lines.

    PubMed

    Carbonnelle, D; Pondaven, P; Morancais, M; Masse, G; Bosch, S; Jacquot, C; Briand, G; Robert, J; Roussakis, C

    1999-01-01

    An aqueous extract of the marine diatom Haslea ostrearia (Simonsen) was studied for its antiproliferative properties against human solid tumors: lung carcinoma (NSCLC-N6), kidney carcinoma (E39) and melanoma (M96). These types of carcinoma are particularly chemoresistant. The extract has a potent cytostatic effect in vitro on the three cell lines and blocks the NSCLC-N6 line in the G1/S phase of the cell cycle. Moreover, the extract strongly inhibits tumor growth of NSCLC-N6 bearing nude mice. These preliminary results indicate that the aqueous extract of Haslea ostrearia exhibits inhibitory effects both in vitro and in vivo against solid carcinoma lines, suggesting the presence of a new potent antitumor agent in the aqueous algal homogenate. PMID:10226609

  10. Differential transcription of the human spermidine/spermine N1-acetyltransferase (SSAT) gene in human lung carcinoma cells.

    PubMed Central

    Xiao, L; Casero, R A

    1996-01-01

    The expression of spermidine/spermine N1-acetyltransferase (SSAT), the rate-limiting enzyme in the catabolism of polyamines, is highly regulated by a number of factors including the natural polyamines and their analogues. The phenotype-specific cytotoxicity that occurs in response to a class of polyamine analogues, the diethylpolyamines, is associated with a phenotype-specific superinduction of SSAT in human non-small-cell lung carcinomas, whereas in non-responding cell types, including the small-cell lung carcinomas, the superinduction of SSAT does not occur. In this study, we have investigated the molecular basis of this phenotype-specific SSAT induction in human lung carcinoma cells in response to N1,N12-diethylspermine (BESpm). To facilitate the study of transcriptional regulation, we have cloned and characterized 11 kb of the human SSAT locus, including 3500 bp of the 5' promoter region. Nuclear run-on transcription studies suggest that the initial induction of SSAT results from an increase in the rate of gene transcription. Results from Northern blot analysis and ribonuclease protection assays indicate a differential expression of SSAT mRNA between the analogue-responsive H157 and non-responsive H82 cells. There is no detectable SSAT mRNA in H82 cells, even after a 24-h analogue treatment, whereas SSAT mRNA in H157 cells was detectable by Northern blot analysis and increased more than 100-fold following drug exposure. Furthermore, nuclear run-on transcription assays do not detect any active transcription of SSAT gene in either treated or untreated H82 cells. These results indicate that at least one component of the phenotype-specific induction of SSAT appears to be due to differences in transcriptional regulation of the gene. In addition, mapping of DNase I-hypersensitive sites of the SSAT gene suggest that the cell type-specific promoter/enhancer utilization may control the expression of the SSAT gene in differentially sensitive cell types in vivo. PMID

  11. Lung squamous cell carcinoma mRNA expression subtypes are reproducible, clinically important and correspond to different normal cell types

    PubMed Central

    Wilkerson, Matthew D.; Yin, Xiaoying; Hoadley, Katherine A.; Liu, Yufeng; Hayward, Michele C.; Cabanski, Christopher R.; Muldrew, Kenneth; Miller, C. Ryan; Randell, Scott H.; Socinski, Mark A.; Parsons, Alden M.; Funkhouser, William K.; Lee, Carrie B.; Roberts, Patrick J.; Thorne, Leigh; Bernard, Philip S.; Perou, Charles M.; Hayes, D. Neil

    2010-01-01

    Purpose Lung squamous cell carcinoma (SCC) is clinically and genetically heterogeneous and current diagnostic practices do not adequately substratify this heterogeneity. A robust, biologically-based SCC subclassification may describe this variability and lead to more precise patient prognosis and management. We sought to determine if SCC mRNA expression subtypes exist, are reproducible across multiple patient cohorts, and are clinically relevant. Experimental Design Subtypes were detected by unsupervised consensus clustering in five published discovery cohorts of mRNA microarrays, totaling 382 SCC patients. An independent validation cohort of 56 SCC patients was collected and assayed by microarrays. A nearest-centroid subtype predictor was built using discovery cohorts. Validation cohort subtypes were predicted and evaluated for confirmation. Subtype survival outcome, clinical covariates, and biological processes were compared by statistical and bioinformatic methods. Results Four lung SCC mRNA expression subtypes, named primitive, classical, secretory, and basal, were detected and independently validated (P < 0.001). The primitive subtype had the worst survival outcome (P < 0.05) and is an independent predictor of survival (P < 0.05). Tumor differentiation and patient sex were associated with subtype. The subtypes’ expression profiles contained distinct biological processes (primitive – proliferation, classical – xeniobiotics metabolism, secretory – immune response, basal – cell adhesion) and suggested distinct pharmacologic interventions. Comparison to lung model systems revealed distinct subtype to cell type correspondence. Conclusions Lung SCC consists of four mRNA expression subtypes that have different survival outcomes, patient populations, and biological processes. The subtypes stratify patients for more precise prognosis and targeted research. PMID:20643781

  12. Berberine suppresses Id-1 expression and inhibits the growth and development of lung metastases in hepatocellular carcinoma.

    PubMed

    Tsang, Chi Man; Cheung, Kenneth Chat Pan; Cheung, Yuk Chun; Man, Kwan; Lui, Vivian Wai-Yan; Tsao, Sai Wah; Feng, Yibin

    2015-03-01

    Hepatocellular carcinoma (HCC) is an invasive cancer with a high rate of recurrence and metastasis. Agents with anti-proliferative as well as anti-metastatic activity will be ideal for effective treatment. Here, we demonstrated that berberine, an isoquinoline alkaloid, harbored potent anti-metastatic and anti-proliferative activities in vivo. Using an orthotopic model of HCC (MHCC-97L), which spontaneously develops lung metastases (one of the most common sites of HCC metastasis), we found that berberine treatment (10mg/kg/2days) significantly reduced lung metastasis from the liver tumors by ~85% (quantitated by bioluminescence emitted from lung metastases). Histological examination also confirmed the reduced incidence and number of lung metastases in berberine-treated mice. Furthermore, berberine effectively suppressed extra-tumor invasion of the primary HCC implant into the surrounding normal liver tissue, illustrating its potent anti-metastatic action in vivo. Consistent with previous reports in other cancer, berberine's anti-tumor activity was accompanied by suppression of cellular proliferation, invasiveness and HIF-1α/VEGF signaling. Strikingly, further mechanistic investigation revealed that berberine exerted profound inhibitory effect on the expression of Id-1, which is a key regulator for HCC development and metastasis. Berberine could suppress the transcription level of Id-1 through inhibiting its promotor activity. Specific downregulation of Id-1 by knocking down its RNA transcripts in HCC cells inhibited cellular growth, invasion and VEGF secretion, demonstrating the functional relevance of Id-1 downregulation induced by berberine. Lastly, berberine's anti-proliferative and anti-invasive activities could be partially rescued by Id-1 overexpression in HCC models, revealing a novel anti-cancer/anti-invasive mechanism of berberine via Id-1 suppression. PMID:25496992

  13. Is VATS lobectomy standard of care for operable non-small cell lung cancer?

    PubMed

    Vannucci, Fernando; Gonzalez-Rivas, Diego

    2016-10-01

    Video-Assisted Thoracic Surgery (VATS) for treatment of lung cancer is being increasingly applied worldwide in the last few years. Since its introduction, many publications have been providing strong evidences that this minimally invasive approach is feasible, safe and oncologically efficient; offering to patients several advantages over traditional open thoracotomy, particularly for early-stage disease (I and II). The application of VATS for locally advanced disease treatment has also been largely described, but probably requires a further level of experience, which is more likely to be found in reference centers, with skilled experts. Although a large multi-institutional prospective randomized-controlled trial is the best way to confirm the superiority of one technique over another, such study comparing VATS versus open lobectomy for lung cancer is unlikely to ever come out. And in this scenario, retrospective data remains as the most reliable source of scientific information. Based on a literature review, the main objective of this article is to discuss to what extent VATS lobectomy can be considered the gold standard in the surgical treatment of lung cancer, taking into account the most important comparison aspects between the minimally invasive approach and open thoracotomy technique. This review addresses questions regarding lymph node dissection, oncologic efficacy, extended resections beyond standard lobectomy, post-operative complications/pain/quality of life, survival rates and the present limits of indication (and contraindication) for VATS, in order to define the real role of this technique on the surgical treatment of lung cancer in a minimally invasive, but safe and effective manner. PMID:27597290

  14. Lung cancer - non-small cell

    MedlinePlus

    Cancer - lung - non-small cell; Non-small cell lung cancer; NSCLC; Adenocarcinoma - lung; Squamous cell carcinoma - lung ... Smoking causes most cases (around 90%) of lung cancer. The risk depends on the number of cigarettes ...

  15. Comparison of survival in patients with non-oat cell carcinoma of lung using various types of treatment modalities

    SciTech Connect

    Akbiyik, N.; Garvey, J.; Kalra, J.; Alexander, L.

    1982-09-01

    From 1967-1977, 560 patients with carcinoma of the lung were seen. Of these, 73 patients underwent lobectomy/pneumonectomy with/without postoperative radiation; 27 are alive today (Group A). Two hundred and seventy patients had distant metastasis when first seen, or it developed during treatment and so they were excluded from the study (Group B). One hundred ninety-seven patients were inoperable or unresectable intrathoraic unilateral (Group C) and treated with one of the following regimens: (1) High dose split course radiotherapy (RT) 3000 rad in 2 weeks followed by 2 weeks rest, then 3000 rad in 2 weeks (2150 ret). (2) Radiotherapy as in regimen1 followed by combination chemotherapy. (3) Continuous RT 6000 rad in 6 weeks. (4) Radiotherapy as in regimen3 followed by combination chemotherapy. (5) Combination chemotherapy alone. RT was administered by /sup 60/Cobalt unit. The survival percentages are discussed later. Chemotherapeutic agents consisted of 2 different drug regimens: vincristine + cyclophosphamide + adriamycin or cyclophosphamide + methotrexate + vincristine CCNU. The 5 month to 5 year survivals in Group C patients treated with two forms of RT techniques were comparable with RT + chemotherapy. Patients receiving chemotherapy alone had a shorter survival rate than those treated with RT alone. In July 1976 a new protocol was started for Stage II squamous cell carcinoma of the lung in which 22 patients received 5000 rad in 5 weeks and were randomized for immunotherapy to receive (a) Methanol Extract Residue (MER) every 4 weeks. (b) VAC (Vincristine) 1.4mg/m/sup 2/IV + adriamycin 50 mg/m/sup 2/IV + cyclophosphamide 500 mg/m/sup 2/IV every 4 weeks or (c) MER + VAC every 4 months. Median survivals for the different regimens were not statistically significant.

  16. MT103 inhibits tumor growth with minimal toxicity in murine model of lung carcinoma via induction of apoptosis.

    PubMed

    Jasinski, Piotr; Zwolak, Pawel; Isaksson Vogel, Rachel; Bodempudi, Vidya; Terai, Kaoru; Galvez, Jorge; Land, David; Dudek, Arkadiusz Z

    2011-10-01

    Molecular topology (MT) was used to develop quantitative structure-activity relationship (QSAR) models to screen databases for new anticancer compounds. One of the selected compounds was MT103, an isoborneol derivative, with a promising profile predicted to slow tumor growth through pro-apoptotic signaling and protein kinase C inhibition. We found that MT103 inhibited the growth of a wide variety of cancer cell types as verified by the NCI-60 cancer cell line panel. MTT cell viability assay showed that MT103 inhibited 50% of the growth of HOP-92, ACHN, NCI-H226, MCF-7, and A549 cancer cell lines at much lower concentrations than that required for HUVECs and human fibroblasts. MT103 stimulated apoptosis in NCI-H226 lung carcinoma cells as measured by oligonucleosomal DNA fragmentation. However, protein kinase C was not targeted by MT103, as predicted by in silico modeling. MT103 slowed in vivo tumor growth and metastatic spread of NCI-H226 cells injected subcutaneously into NOD/SCID mice, without eliciting any severe adverse events as monitored by animal survival, blood serum analysis, and histological analysis of organs. Oral administration of MT103 nanoparticles (200 nm in diameter), which were generated with ElectroNanospray™ technology, inhibited in vivo growth of HOP-92 lung carcinoma cells almost as effectively as intraperitoneal injections of cisplatin. Taken together, our study of a novel anti-cancer drug identified using a molecular topology-based approach to drug discovery demonstrates that MT103 has anti-tumor activity in vitro and in vivo, although additional studies are needed to elucidate its mechanism of action. PMID:20396929

  17. Isolating and Testing Circulating Tumor DNA and Soluble Immune Markers During the Course of Treatment for Lung Cancer

    ClinicalTrials.gov

    2016-07-11

    Lung Cancer; Lung Neoplasms; Cancer of Lung; Cancer of the Lung; Neoplasms, Lung; Neoplasms, Pulmonary; Pulmonary Cancer; Pulmonary Neoplasms; Carcinoma, Non-small-cell Lung; Adenocarcinoma; Squamous Cell Carcinoma

  18. Effects of the Demethylating Agent, 5-Azacytidine, on Expression of the Kallikrein-Kinin Genes in Carcinoma Cells of the Lung and Pleura

    PubMed Central

    Wong, Joshua; Sia, Yee Yen; Misso, Neil L.; Aggarwal, Shashi; Ng, Angeline; Bhoola, Kanti D.

    2011-01-01

    Tissue kallikrein (KLK1) and plasma kallikrein (KLKB1) may regulate the growth and proliferation of tumours of the lung and pleura, through the generation of kinin peptides that signal through the kinin B1 (BDKRB1) and B2 (BDKRB2) receptors. The development and progression of cancer results from genetic mutations, as well as epigenetic changes that include methylation of DNA at CpG islands. The aim of this study was to assess whether expression of the kallikrein-kinin genes in lung cancer and mesothelioma cells is regulated by DNA methylation. Quantitative reverse transcriptase-PCR and immunocytochemistry showed differences in the basal expression of the kallikrein-kinin genes and proteins in lung carcinoma and mesothelioma cells, compared with non-malignant lung epithelial and mesothelial cells, respectively. Following treatment with the demethylating agent, 5-azacytidine (5-AZA), KLKB1 mRNA expression was consistently increased in both lung carcinoma and mesothelioma cells, whereas KLK1, BDKRB1 and BDKRB2 mRNA expression was decreased or unchanged. Increased expression of KLKB1 after 5-AZA treatment suggests it may function as a tumour suppressor gene in cancers of the lung and pleura. Studies on DNA methylation of the kallikrein-kinin genes will enhance understanding of their role in carcinogenesis and provide insights into the importance of kallikreins as tumour biomarkers. PMID:21904690

  19. [Polychemotherapy of large cell carcinoma of the lung: a case of complete remission].

    PubMed

    Spaghi, A; Costa, D; Gangarossa, I; Castoldi, O; Pasotti, D; Albergati, M G; Nastasi, G

    1989-01-01

    A case of a patient with large cell pulmonary carcinoma is presented. Being inoperable, the patient was treated at first with multiple drug chemotherapy and the result was the disappearance of the pulmonary lesions. The unusual favourable therapeutic response and the protocols of polychemotherapy used are discussed. PMID:2544780

  20. A propensity score matching analysis of survival following segmentectomy or wedge resection in early-stage lung invasive adenocarcinoma or squamous cell carcinoma

    PubMed Central

    Zhang, Yang; Sun, Yihua; Chen, Haiquan

    2016-01-01

    Purpose: To compare the survival outcomes following segmentectomy or wedge resection in early-stage lung cancer. Methods: A total of 5880 patients with invasive lung adenocarcinoma or squamous cell carcinoma from the Surveillance, Epidemiology, and End Results (SEER) database were included in this study, of which 1156 received segmentectomy. Baseline characteristics were balanced using propensity score methods. Cox regression analysis was used to compare overall survival (OS) and lung cancer-specific survival (LCSS) following segmentectomy or wedge resection after matching patients based on propensity scores. Results: Overall, patients undergoing segmentectomy and wedge resection had no significant different OS and LCSS both in the invasive adenocarcinoma group and the squamous cell carcinoma group. Segmentectomy was associated with improved OS (hazard ratio = 0.626, 95% confidence interval: 0.457-0.858, P = 0.004) and LCSS (hazard ratio = 0.643, 95% CI: 0.440-0.939, P = 0.022) in invasive adenocarcinoma patients ≤ 65 years old. In patients with ≤ 2 cm invasive adenocarcinoma, segmentectomy was associated with significantly better OS (hazard ratio = 0.811, 95% confidence interval: 0.666-0.988, P = 0.038). Conclusion: Survival following segmentectomy or wedge resection was generally equivalent in lung invasive adenocarcinoma and squamous cell carcinoma. However, invasive adenocarcinoma patients who were ≤ 65 years or had tumors ≤ 2 cm in size may have improved survival outcomes after segmentectomy. PMID:26871600

  1. FRAGMATIC: A randomised phase III clinical trial investigating the effect of fragmin® added to standard therapy in patients with lung cancer

    PubMed Central

    2009-01-01

    Background Venous thromboembolism (VTE) occurs when blood clots in the leg, pelvic or other deep vein (deep vein thrombosis) with or without transport of the thrombus into the pulmonary arterial circulation (pulmonary embolus). VTE is common in patients with cancer and is increased by surgery, chemotherapy, radiotherapy and disease progression. Low molecular weight heparin (LMWH) is routinely used to treat VTE and some evidence suggests that LMWH may also have an anticancer effect, by reduction in the incidence of metastases. The FRAGMATIC trial will assess the effect of adding dalteparin (FRAGMIN), a type of LMWH, to standard treatment for patients with lung cancer. Methods/Design The study design is a randomised multicentre phase III trial comparing standard treatment and standard treatment plus daily LMWH for 24 weeks in patients with lung cancer. Patients eligible for this study must have histopathological or cytological diagnosis of primary bronchial carcinoma (small cell or non-small cell) within 6 weeks of randomisation, be 18 or older, and must be willing and able to self-administer 5000 IU dalteparin by daily subcutaneous injection or have it administered to themselves or by a carer for 24 weeks. A total of 2200 patients will be recruited from all over the UK over a 3 year period and followed up for a minimum of 1 year after randomisation. Patients will be randomised to one of the two treatment groups in a 1:1 ratio, standard treatment or standard treatment plus dalteparin. The primary outcome measure of the trial is overall survival. The secondary outcome measures include venous thrombotic event (VTE) free survival, serious adverse events (SAEs), metastasis-free survival, toxicity, quality of life (QoL), levels of breathlessness, anxiety and depression, cost effectiveness and cost utility. Trial registration Current Controlled Trials ISRCTN80812769 PMID:19807917

  2. Small cell mesothelioma: A rare entity and diagnostic pitfall mimicking small cell lung carcinoma on fine-needle aspiration.

    PubMed

    Zhang, Yanhong; Afify, Alaa; Gandour-Edwards, Regina F; Bishop, John W; Huang, Eric C

    2016-06-01

    Small cell mesothelioma (SCM) is an extremely rare variant of epithelioid mesothelioma that can be mistaken for other forms of small round blue cell tumors, particularly small cell lung carcinoma (SCLC). Here, we describe a fine-needle aspiration (FNA) from a pleural lesion in a 75-year-old man with a history of known asbestos exposure. The FNA revealed cohesive clusters of uniform small round blue cells with high nuclear-to-cytoplasmic ratio, finely powdery chromatin, small inconspicuous nucleoli, and scant amount of cytoplasm. Mitoses were infrequent and nuclear molding was absent. Immunochemical profile supported a mesothelial origin, which was later confirmed by pleurectomy with a diagnosis of SCM. This report demonstrates the difficulties in cytologic evaluation of lung FNAs in differentiating SCM from SCLC or other small round blue cell tumors. As therapy differs for SCM, early recognition of the cytologic features is essential in making the correct diagnosis needed for appropriate clinical management. Diagn. Cytopathol. 2016;44:526-529. © 2016 Wiley Periodicals, Inc. PMID:26952387

  3. Metastatic hepatocellular carcinoma of the maxillary sinus: a rare autopsy case without lung metastasis and a review.

    PubMed

    Okada, H; Kamino, Y; Shimo, M; Kitamura, E; Katoh, T; Nishimura, H; Akimoto, Y; Kaneda, T; Hinata, M; Yamamoto, H

    2003-02-01

    A rare case of metastatic hepatocellular carcinoma (HCC) of the maxillary sinus in a 67-year-old man is reported along with the findings at autopsy. A fine needle aspiration biopsy specimen revealed a characteristic tumour structure resembling primary HCC. At autopsy, metastatic lesions were recognized in the bilateral adrenals, spleen, sternum, vertebrae and lymph node at the lesser curvature of the stomach, but not in the lung, suggesting that the HCC had metastasized to the maxillary sinus via the plexus venous vertebralis and/or the azygos vein, or lymph duct. In our reviewed 29 cases of metastatic HCC in the oro-maxillofacial region, most patients were men in the 50- to 70-year age range. At least 11 cases did not have lung metastasis, and in 18, metastasis to the oro-maxillofacial region was the first sign of HCC. One should be aware of the possibility to encounter the oral lesion as first sign of metastatic HCC. PMID:12653243

  4. Apoptotic properties of polysaccharide isolated from fruiting bodies of medicinal mushroom Fomes fomentarius in human lung carcinoma cell line

    PubMed Central

    Kim, Sang Ho; Jakhar, Rekha; Kang, Sun Chul

    2014-01-01

    Mushrooms are known to complement chemotherapy and radiation therapy by countering the side effects of cancer. Recently, there has been great interest in isolation of novel bioactive compounds from mushrooms due to their numerous health beneficial effects. Chemically water-extractable polysaccharide (MFKF-AP1β), with a molecular weight of 12 kDa, was isolated from fruiting bodies of mushroom Fomes fomentarius. In this research, we investigated the anti-tumor effects of MFKF-AP1β on human lung carcinoma A549 cells. Results showed that MFKF-AP1β markedly inhibited A549 cell growth in a dose-dependent manner based on the amount of lactate dehydrogenase (LDH) released and morphological alterations. In addition, MFKF-AP1β induced cellular apoptosis by causing single-stranded DNA breakage, as evidenced by apoptosis assay. Furthermore, MFKF-AP1β (25–100 μg/ml) significantly induced single-stranded DNA breakage in A549 cells, as shown by comet assay. Taken together, our results demonstrate that MFKF-AP1β has strong anti-tumor effects mediated through induction of apoptosis. Therefore, MFKF-AP1β could be useful in lung chemotherapy. PMID:26150756

  5. miR-204 suppresses non-small-cell lung carcinoma (NSCLC) invasion and migration by targeting JAK2.

    PubMed

    Wang, P; Lv, H Y; Zhou, D M; Zhang, E N

    2016-01-01

    Aberrant expression of microRNA is associated with the development and progression of cancers. MicroRNA-204 (miR-204) down-regulation has been previously demonstrated in non-small-cell lung carcinoma (NSCLC); however, the underlying mechanism by which miR-204 suppresses tumorigenesis in NSCLC remains elusive. In this study, miR-204 expression was found to be down-regulated, and that of Janus kinase 2 (JAK2) was found to be up-regulated in four NSCLC cell lines (A549, H1299, H1650, and H358) compared to the normal lung cell line. The overexpression of miR-204 suppressed the invasive and migratory capacities of H1299 cells. A luciferase assay confirmed that the binding of miR-124 to the -untranslated region of JAK2 inhibited the expression of JAK2 proteins in H1299 cells. JAK-2 overexpression effectively reversed miR-204-repressed NSCLC metastasis. Taken together, our findings revealed that miR-204 functions as a tumor suppressor in NSCLC by targeting JAK2, and that miR-204 may therefore serve as a biomarker for the diagnosis and treatment of NSCLC. PMID:27323056

  6. Pharmacokinetics of the far red absorbing octa-alpha-butyloxy-zinc phthalocyanine in Lewis lung carcinoma bearing mice

    NASA Astrophysics Data System (ADS)

    Dressler, Cathrin; Ismail, M. Samy; Nowak, Christian; Herter, Ralf; Senz, Rainier G.; Hagemann, Roland; Roeder, Beate; Berlien, Hans-Peter

    1995-01-01

    The newly synthesized potential photosensitizer octa-(alpha) -butyloxy-zinc phthalocyanine (8-(alpha) -bo-ZnPc) is characterized by a high absorption coefficient at the far red wavelength 735 nm and a good singlet oxygen quantum yield. The pharmacokinetics of 8- (alpha) -bo-ZnPc were studied on the Lewis lung carcinoma in mice after i.v. administration of 7.8 micrometers ole/kg body weight solubilized in PBS with 1% Tween 80 at 2, 6, 12, 24, 48 and 168 hour incubation intervals. The accumulated dye contents were chemically extracted from selected tissues and the concentrations were measured by absorption spectroscopy. The parenchymatous organs, liver and spleen, showed maximum 8-(alpha) -bo-ZnPc concentrations after 6 h incubation (33 nmole/g liver and 5 nmole/g spleen, respectively). An extensive uptake was detected in the lung where concentrations higher than 90 nmole/g tissue were measured in the 6, 12, 24, and 48 hour extracts. The malignant tissue did not accumulate higher 8-(alpha) -bo-ZnPc concentrations than 0.4 nmole/g tumor during the entire investigation period. The dye contents extracted from muscle, representing normal tumor surrounding tissue, and skin were even lower and never exceeded 0.11 nmole/g muscle (6 h) and 0.21 nmole/g skin (2 h), respectively.

  7. Novel Candidate Key Drivers in the Integrative Network of Genes, MicroRNAs, Methylations, and Copy Number Variations in Squamous Cell Lung Carcinoma

    PubMed Central

    Cai, Yu-dong

    2015-01-01

    The mechanisms of lung cancer are highly complex. Not only mRNA gene expression but also microRNAs, DNA methylation, and copy number variation (CNV) play roles in tumorigenesis. It is difficult to incorporate so much information into a single model that can comprehensively reflect all these lung cancer mechanisms. In this study, we analyzed the 129 TCGA (The Cancer Genome Atlas) squamous cell lung carcinoma samples with gene expression, microRNA expression, DNA methylation, and CNV data. First, we used variance inflation factor (VIF) regression to build the whole genome integrative network. Then, we isolated the lung cancer subnetwork by identifying the known lung cancer genes and their direct regulators. This subnetwork was refined by the Bayesian method, and the directed regulations among mRNA genes, microRNAs, methylations, and CNVs were obtained. The novel candidate key drivers in this refined subnetwork, such as the methylation of ARHGDIB and HOXD3, microRNA let-7a and miR-31, and the CNV of AGAP2, were identified and analyzed. On three large public available lung cancer datasets, the key drivers ARHGDIB and HOXD3 demonstrated significant associations with the overall survival of lung cancer patients. Our results provide new insights into lung cancer mechanisms. PMID:25802847

  8. Multidimensional effects of biologically synthesized silver nanoparticles in Helicobacter pylori, Helicobacter felis, and human lung (L132) and lung carcinoma A549 cells

    NASA Astrophysics Data System (ADS)

    Gurunathan, Sangiliyandi; Jeong, Jae-Kyo; Han, Jae Woong; Zhang, Xi-Feng; Park, Jung Hyun; Kim, Jin-Hoi

    2015-02-01

    Silver nanoparticles (AgNPs) are prominent group of nanomaterials and are recognized for their diverse applications in various health sectors. This study aimed to synthesize the AgNPs using the leaf extract of Artemisia princeps as a bio-reductant. Furthermore, we evaluated the multidimensional effect of the biologically synthesized AgNPs in Helicobacter pylori, Helicobacter felis, and human lung (L132) and lung carcinoma (A549) cells. UV-visible (UV-vis) spectroscopy confirmed the synthesis of AgNPs. X-ray diffraction (XRD) indicated that the AgNPs are specifically indexed to a crystal structure. The results from Fourier transform infrared spectroscopy (FTIR) indicate that biomolecules are involved in the synthesis and stabilization of AgNPs. Dynamic light scattering (DLS) studies showed the average size distribution of the particle between 10 and 40 nm, and transmission electron microscopy (TEM) confirmed that the AgNPs were significantly well separated and spherical with an average size of 20 nm. AgNPs caused dose-dependent decrease in cell viability and biofilm formation and increase in reactive oxygen species (ROS) generation and DNA fragmentation in H. pylori and H. felis. Furthermore, AgNPs induced mitochondrial-mediated apoptosis in A549 cells; conversely, AgNPs had no significant effects on L132 cells. The results from this study suggest that AgNPs could cause cell-specific apoptosis in mammalian cells. Our findings demonstrate that this environmentally friendly method for the synthesis of AgNPs and that the prepared AgNPs have multidimensional effects such as anti-bacterial and anti-biofilm activity against H. pylori and H. felis and also cytotoxic effects against human cancer cells. This report describes comprehensively the effects of AgNPs on bacteria and mammalian cells. We believe that biologically synthesized AgNPs will open a new avenue towards various biotechnological and biomedical applications in the near future.

  9. Enediyne lidamycin enhances the effect of epidermal growth factor receptor tyrosine kinase inhibitor, gefitinib, in epidermoid carcinoma A431 cells and lung carcinoma H460 cells.

    PubMed

    Liu, Hong; Li, Liang; Li, Xing-Qi; Liu, Xiu-Jun; Zhen, Yong-Su

    2009-01-01

    Gefitinib, a low-molecular-weight epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, is effective in a wide variety of tumor types. Preclinical studies have shown potentiated antitumor efficacies of this agent in combination with chemotherapy or radiotherapy. The antitumor antibiotic lidamycin (LDM) showed extremely potent cytotoxicity in vitro and marked therapeutic effect in vivo. In this report, the cytotoxic and biochemical activity of LDM and gefitinib on human epidermoid carcinoma A431 cells and human large cell lung cancer H460 cells as a single agent or in combination has been evaluated. In the MTT assay, LDM showed much more potent cytotoxicity than gefitinib to both cell lines. A431 cells with a highly EGFR-expressing level were more sensitive to gefitinib than H460 cells, which expressed EGFR at an intermediate level. LDM plus gefitinib showed potentiation of antiproliferative activity and apoptosis induction, which were associated with downregulation of EGFR signaling pathway and nuclear factor-kappa B expression, and the increase of cleaved poly (adenosine diphosphate-ribose) polymerase in the two cell lines, although to a lesser degree in H460 cells. Combined treatment induced G1 phase arrest similar to that of gefitinib alone in A431 cells and intensified G2/M phase accumulation in H460 cells. The above results indicate that LDM potentiates the effects of gefitinib in both gefitinib sensitive and less sensitive cells in association with enhanced inhibition of EGFR-dependent signaling. PMID:19342999

  10. The EGFR mutation status affects the relative biological effectiveness of carbon-ion beams in non-small cell lung carcinoma cells

    PubMed Central

    Amornwichet, Napapat; Oike, Takahiro; Shibata, Atsushi; Nirodi, Chaitanya S.; Ogiwara, Hideaki; Makino, Haruhiko; Kimura, Yuka; Hirota, Yuka; Isono, Mayu; Yoshida, Yukari; Ohno, Tatsuya; Kohno, Takashi; Nakano, Takashi

    2015-01-01

    Carbon-ion radiotherapy (CIRT) holds promise to treat inoperable locally-advanced non-small cell lung carcinoma (NSCLC), a disease poorly controlled by standard chemoradiotherapy using X-rays. Since CIRT is an extremely limited medical resource, selection of NSCLC patients likely to benefit from it is important; however, biological predictors of response to CIRT are ill-defined. The present study investigated the association between the mutational status of EGFR and KRAS, driver genes frequently mutated in NSCLC, and the relative biological effectiveness (RBE) of carbon-ion beams over X-rays. The assessment of 15 NSCLC lines of different EGFR/KRAS mutational status and that of isogenic NSCLC lines expressing wild-type or mutant EGFR revealed that EGFR-mutant NSCLC cells, but not KRAS-mutant cells, show low RBE. This was attributable to (i) the high X-ray sensitivity of EGFR-mutant cells, since EGFR mutation is associated with a defect in non-homologous end joining, a major pathway for DNA double-strand break (DSB) repair, and (ii) the strong cell-killing effect of carbon-ion beams due to poor repair of carbon-ion beam-induced DSBs regardless of EGFR mutation status. These data highlight the potential of EGFR mutation status as a predictor of response to CIRT, i.e., CIRT may show a high therapeutic index in EGFR mutation-negative NSCLC. PMID:26065573

  11. The EGFR mutation status affects the relative biological effectiveness of carbon-ion beams in non-small cell lung carcinoma cells.

    PubMed

    Amornwichet, Napapat; Oike, Takahiro; Shibata, Atsushi; Nirodi, Chaitanya S; Ogiwara, Hideaki; Makino, Haruhiko; Kimura, Yuka; Hirota, Yuka; Isono, Mayu; Yoshida, Yukari; Ohno, Tatsuya; Kohno, Takashi; Nakano, Takashi

    2015-01-01

    Carbon-ion radiotherapy (CIRT) holds promise to treat inoperable locally-advanced non-small cell lung carcinoma (NSCLC), a disease poorly controlled by standard chemoradiotherapy using X-rays. Since CIRT is an extremely limited medical resource, selection of NSCLC patients likely to benefit from it is important; however, biological predictors of response to CIRT are ill-defined. The present study investigated the association between the mutational status of EGFR and KRAS, driver genes frequently mutated in NSCLC, and the relative biological effectiveness (RBE) of carbon-ion beams over X-rays. The assessment of 15 NSCLC lines of different EGFR/KRAS mutational status and that of isogenic NSCLC lines expressing wild-type or mutant EGFR revealed that EGFR-mutant NSCLC cells, but not KRAS-mutant cells, show low RBE. This was attributable to (i) the high X-ray sensitivity of EGFR-mutant cells, since EGFR mutation is associated with a defect in non-homologous end joining, a major pathway for DNA double-strand break (DSB) repair, and (ii) the strong cell-killing effect of carbon-ion beams due to poor repair of carbon-ion beam-induced DSBs regardless of EGFR mutation status. These data highlight the potential of EGFR mutation status as a predictor of response to CIRT, i.e., CIRT may show a high therapeutic index in EGFR mutation-negative NSCLC. PMID:26065573

  12. [Single-dose palliative radiotherapy in inoperable non-small-cell lung carcinoma].

    PubMed

    Scolaro, T; Bacigalupo, A; Giudici, S; Guenzi, M; Vitale, V

    1995-12-01

    The treatment of choice for advanced inoperable non-small cell lung cancer (NSCLC) is radiation therapy. Palliative radiotherapy schedules vary considerably in different centers, but a 30-Gy dose given in ten fractions over two weeks is a typical standard schedule. Our study was aimed at investigating whether a shorter course of only one 10-Gy fraction allows good palliation in the treatment of inoperable NSCLC patients whose main symptoms are related to an intrathoracic lesion. Patients of both sexes and any age, untreated with radiotherapy, with inoperable and histologically or cytologically proved NSCLC were examined. Seventeen patients, too advanced for radical "curative" radiotherapy and whose main symptoms were related to primary intrathoracic lesions, entered the study even though they had metastases. On admission, 76% (13/17) of patients had cough 76% (13/17) dyspnea, 70.7% (12/17) chest pain and 23.6% (4/17) hemoptysis. They received a single dose of 10 Gy, delivered with an 18-Mv linear accelerator via anteroposteriorly opposing portals without spinal cord shielding. Treatment volume usually included the macroscopically detected lesion identified with a CT simulator. Palliation of symptoms was achieved in high rates of patients: 46% for cough, 69% for dyspnea, 83% for pain and 75% for hemoptysis. These results were obtained within one month of treatment. Unfortunately, palliation of symptoms did not last long, decreasing to 42% within two months of the end of treatment and to 32% at three months. Four patients were retreated, one patient three months and three patients two months after the end of radiotherapy. Ten Gy to the target volume were administered as retreatment with spinal cord shielding. Side-effects were mild: nausea in 3 patients (17%), vomiting in one patient (5%) and grade-II dysphagia in two patients were observed and classified according to WHO criteria. Pain increased 24 hours after radiotherapy in five patients. We can conclude that

  13. Rule discovery and distance separation to detect reliable miRNA biomarkers for the diagnosis of lung squamous cell carcinoma

    PubMed Central

    2014-01-01

    Background Altered expression profiles of microRNAs (miRNAs) are linked to many diseases including lung cancer. miRNA expression profiling is reproducible and miRNAs are very stable. These characteristics of miRNAs make them ideal biomarker candidates. Method This work is aimed to detect 2-and 3-miRNA groups, together with specific expression ranges of these miRNAs, to form simple linear discriminant rules for biomarker identification and biological interpretation. Our method is based on a novel committee of decision trees to derive 2-and 3-miRNA 100%-frequency rules. This method is applied to a data set of lung miRNA expression profiles of 61 squamous cell carcinoma (SCC) samples and 10 normal tissue samples. A distance separation technique is used to select the most reliable rules which are then evaluated on a large independent data set. Results We obtained four 2-miRNA and three 3-miRNA top-ranked rules. One important rule is that: If the expression level of miR-98 is above 7.356 and the expression level of miR-205 is below 9.601 (log2 quantile normalized MirVan miRNA Bioarray signals), then the sample is normal rather than cancerous with specificity and sensitivity both 100%. The classification performance of our best miRNA rules remarkably outperformed that by randomly selected miRNA rules. Our data analysis also showed that miR-98 and miR-205 have two common predicted target genes FZD3 and RPS6KA3, which are actually genes associated with carcinoma according to the Online Mendelian Inheritance in Man (OMIM) database. We also found that most of the chromosomal loci of these miRNAs have a high frequency of genomic alteration in lung cancer. On the independent data set (with balanced controls), the three miRNAs miR-126, miR-205 and miR-182 from our best rule can separate the two classes of samples at the accuracy of 84.49%, sensitivity of 91.40% and specificity of 77.14%. Conclusion Our results indicate that rule discovery followed by distance separation is a

  14. Survival prognostic factors for patients with synchronous brain oligometastatic non-small-cell lung carcinoma receiving local therapy

    PubMed Central

    Bai, Hao; Xu, Jianlin; Yang, Haitang; Jin, Bo; Lou, Yuqing; Wu, Dan; Han, Baohui

    2016-01-01

    Introduction Clinical evidence for patients with synchronous brain oligometastatic non-small-cell lung carcinoma is limited. We aimed to summarize the clinical data of these patients to explore the survival prognostic factors for this population. Methods From September 1995 to July 2011, patients with 1–3 synchronous brain oligometastases, who were treated with stereotactic radiosurgery (SRS) or surgical resection as the primary treatment, were identified at Shanghai Chest Hospital. Results A total of 76 patients (22 patients underwent brain surgery as primary treatment and 54 patients received SRS) were available for survival analysis. The overall survival (OS) for patients treated with SRS and brain surgery as the primary treatment were 12.6 months (95% confidence interval [CI] 10.3–14.9) and 16.4 months (95% CI 8.8–24.1), respectively (adjusted hazard ratio =0.59, 95% CI 0.33–1.07, P=0.08). Among 76 patients treated with SRS or brain surgery, 21 patients who underwent primary tumor resection did not experience a significantly improved OS (16.4 months, 95% CI 9.6–23.2), compared with those who did not undergo resection (11.9 months, 95% CI 9.7–14.0; adjusted hazard ratio =0.81, 95% CI 0.46–1.44, P=0.46). Factors associated with survival benefits included stage I–II of primary lung tumor and solitary brain metastasis. Conclusion There was no significant difference in OS for patients with synchronous brain oligometastasis receiving SRS or surgical resection. Among this population, the number of brain metastases and stage of primary lung disease were the factors associated with a survival benefit. PMID:27471395

  15. Vitamin D Repletion Reduces the Progression of Premalignant Squamous Lesions in the NTCU Lung Squamous Cell Carcinoma Mouse Model.

    PubMed

    Mazzilli, Sarah A; Hershberger, Pamela A; Reid, Mary E; Bogner, Paul N; Atwood, Kristopher; Trump, Donald L; Johnson, Candace S

    2015-10-01

    The chemopreventive actions of vitamin D were examined in the N-nitroso-tris-chloroethylurea (NTCU) mouse model, a progressive model of lung squamous cell carcinoma (SCC). SWR/J mice were fed a deficient diet (D) containing no vitamin D3, a sufficient diet (S) containing 2,000 IU/kg vitamin D3, or the same diets in combination with the active metabolite of vitamin D, calcitriol (C; 80 μg/kg, weekly). The percentage (%) of the mucosal surface of large airways occupied by dysplastic lesions was determined in mice after treatment with a total dose of 15 or 25 μmol NTCU (N). After treatment with 15 μmol NTCU, the percentages of the surface of large airways containing high-grade dysplastic (HGD) lesions were vitamin D-deficient + NTCU (DN), 22.7% [P < 0.05 compared with vitamin D-sufficient +NTCU (SN)]; DN + C, 12.3%; SN, 8.7%; and SN + C, 6.6%. The extent of HGD increased with NTCU dose in the DN group. Proliferation, assessed by Ki-67 labeling, increased upon NTCU treatment. The highest Ki-67 labeling index was seen in the DN group. As compared with SN mice, DN mice exhibited a three-fold increase (P < 0.005) in circulating white blood cells (WBC), a 20% (P < 0.05) increase in IL6 levels, and a four-fold (P < 0.005) increase in WBC in bronchial lavages. Thus, vitamin D repletion reduces the progression of premalignant lesions, proliferation, and inflammation, and may thereby suppress development of lung SCC. Further investigations of the chemopreventive effects of vitamin D in lung SCC are warranted. PMID:26276745

  16. Water-soluble extract of Saxifraga stolonifera has anti-tumor effects on Lewis lung carcinoma-bearing mice.

    PubMed

    Liu, Dong; Yang, Ping; Zhang, Yu-Qing

    2016-10-01

    Saxifraga stolonifera is an evergreen and herbaceous plant well known in Korea, Japan and western China, which has great potential applications in gardening and pharmacology. The aim of this study is to evaluate the anti-tumor effects of S. stolonifera extraction on lung tumors of Lewis mice. By the measurement of MS/MS, we found that there were four main bioactive components in methanol extract of S. stolonifera, including gallic acid, norbergenin, protocatechuic acid and bergenin, and the results of quantitative analysis showed that the contents of gallic acid, protocatechuic acid and bergenin in methanol extract of S. stolonifera were 5.150, 1.492, 24.559mg/g, respectively. Animal experiment showed that the mean tumor weight of Lewis lung carcinoma-bearing mice treated with water-soluble extract of S. stolonifera was obviously smaller than model group (cis-DDP), and its inhibition rate was 49.2%. In addition, histopathological evaluation and immunohistochemical assay confirmed the anti-tumor effects of S. stolonifera. Investigation of four haematological parameters revealed that the Lewis mice fed with S. stolonifera showed good resilience in the level of leukocyte, haemoglobin, blood platelets and red blood cell compared with the model group. In addition, RT-PCR suggested that the relative expression of pro-apoptosis gene p53, Sox and Bax was enhanced, while the relative expression of anti-apoptosis gene Bcl2 was diminished in comparison with model group. These results suggested that water-soluble extract of S. stolonifera has anti-tumor effects on Lewis lung tumors. PMID:27575479

  17. Identification and validation of S100A7 associated with lung squamous cell carcinoma metastasis to brain.

    PubMed

    Zhang, Hao; Wang, Yinping; Chen, Yue; Sun, Suozhu; Li, Na; Lv, Dongxia; Liu, Chuanjun; Huang, Lingyun; He, Dacheng; Xiao, Xueyuan

    2007-07-01

    To identify potential markers associated with non-small cell lung cancer (NSCLC) metastasis to brain, comparative proteome analysis on two lung squamous cell carcinoma (SCC) cell lines, NCI-H226 and H226Br (the brain metastatic cell line of NCI-H226), was performed using two-dimensional electrophoresis (2-DE) followed by a tandem mass spectrometer with a matrix-assisted laser desorption/ionization (MALDI) source. Twenty differential proteins were identified, of which 6 proteins were up-regulated in H226Br cell compared with NCI-H226 cells, whereas 14 proteins were down-regulated. S100A7 and 14-3-3sigma, two of candidate proteins significantly upregulated and downregulated in H226Br cell, were selected to verify the liability of the differential proteins by Western blot. The results were in accordance with 2-D data. To determine whether S100A7 overexpression is actually associated with SCC metastasis to brain, S100A7 protein was testified in 10 brain metastasis tissues from NSCLC, 38 primary NSCLC tissues including half matched local positive lymph nodes, 5 primary brain tumors and 2 non-cancer brain tissues by immunohistochemistry. Of particular interest to us was that the positive staining of S100A7 could be found in 3/5 (60%) brain metastases tissue from SCC and 8/21 (38%) the primary lung SCC tissues, while no positive staining was observed in the brain metastases tissue from Ad (n=5), the primary adenocarcinoma (Ad) tissues (n=17), the primary brain tumors (n=5), all local positive lymph nodes from the primary NSCLC (n=19) and non-cancer brain tissues (n=2). These findings suggest that S100A7 expression is closely associated with SCC metastasis to brain and may be a potential biomarker for monitoring the development of SCC. PMID:17418446

  18. Monocyte chemotactic protein-1 deficiency reduces spontaneous metastasis of Lewis lung carcinoma in mice fed a high-fat diet.

    PubMed

    Yan, Lin; Sundaram, Sneha

    2016-04-26

    Adipose-produced pro-inflammatory cytokines contribute to obesity and cancer. This 2x2 experiment was designed to investigate effects of monocyte chemotactic protein-1 (MCP-1) deficiency on pulmonary metastasis of Lewis lung carcinoma (LLC) in MCP-1 deficient and wild-type mice fed a modified AIN93G diet containing 16% and 45% of energy from corn oil, respectively. The high-fat diet significantly increased the number and size (cross-sectional area and volume) of lung metastases compared to the AIN93G control diet. Deficiency in MCP-1 reduced lung metastases by 37% in high-fat diet-fed mice; it reduced metastatic cross-sectional area by 46% and volume by 69% compared to wild-type mice. Adipose and plasma concentrations of MCP-1 were significantly higher in high-fat diet-fed wild-type mice than in their AIN93G-fed counterparts; they were not detectable in MCP-1 deficient mice regardless of diet. Plasma concentrations of plasminogen activator inhibitor-1, tumor necrosis factor-α, vascular endothelial growth factor and tissue inhibitor of metalloproteinase-1 were significantly higher in MCP-1 deficient mice compared to wild-type mice. We conclude that adipose-produced MCP-1 contributes to high-fat diet-enhanced metastasis. While MCP-1 deficiency reduces metastasis, the elevation of pro-inflammatory cytokines and angiogenic factors in the absence of MCP-1 may support the metastatic development and growth of LLC in MCP-1 deficient mice. PMID:27028862

  19. Stereotactic body radiation therapy of early-stage non-small-cell lung carcinoma: Phase I study

    SciTech Connect

    McGarry, Ronald C. . E-mail: rmcgarry@iupui.edu; Papiez, Lech; Williams, Mark; Whitford, Tia; Timmerman, Robert D.

    2005-11-15

    Purpose: A Phase I dose escalation study of stereotactic body radiation therapy to assess toxicity and local control rates for patients with medically inoperable Stage I lung cancer. Methods and Materials: All patients had non-small-cell lung carcinoma, Stage T1a or T1b N0, M0. Patients were immobilized in a stereotactic body frame and treated in escalating doses of radiotherapy beginning at 24 Gy total (3 x 8 Gy fractions) using 7-10 beams. Cohorts were dose escalated by 6.0 Gy total with appropriate observation periods. Results: The maximum tolerated dose was not achieved in the T1 stratum (maximum dose = 60 Gy), but within the T2 stratum, the maximum tolerated dose was realized at 72 Gy for tumors larger than 5 cm. Dose-limiting toxicity included predominantly bronchitis, pericardial effusion, hypoxia, and pneumonitis. Local failure occurred in 4/19 T1 and 6/28 T2 patients. Nine local failures occurred at doses {<=}16 Gy and only 1 at higher doses. Local failures occurred between 3 and 31 months from treatment. Within the T1 group, 5 patients had distant or regional recurrence as an isolated event, whereas 3 patients had both distant and regional recurrence. Within the T2 group, 2 patients had solitary regional recurrences, and the 4 patients who failed distantly also failed regionally. Conclusions: Stereotactic body radiation therapy seems to be a safe, effective means of treating early-stage lung cancer in medically inoperable patients. Excellent local control was achieved at higher dose cohorts with apparent dose-limiting toxicities in patients with larger tumors.

  20. Isolated Calcaneal Metastasis: An Unusual Presentation of Lung Carcinoma as Heel Pain.

    PubMed

    Singh, Charanjeet; Gupta, Mamta; Singh, Jagadeesh; Ali, Amjad

    2016-03-01

    A 63-year-old woman initially presented with progressive left foot pain for 3 months, not responding to conservative management. MRI of the left foot showed a suspicious lesion in calcaneus. An open biopsy was consistent with metastatic lung adenocarcinoma. Tc-MDP total-body bone scintigraphy was ordered for possible other bony lesions, and only left calcaneus lesion was identified on bone scan. CT scan of the chest revealed a soft tissue mass in the superior aspect of the right lower lobe. Staging FDG PET/CT showed hypermetabolic right lung mass and left calcaneus lesion. She received chemotherapy and local radiation to the left calcaneus metastatic lesion. PMID:26562577

  1. Lung carcinoma presenting with pathologic femur fracture and false-positive pregnancy test result.

    PubMed

    Maughan, Brandon C; Kamat, Achyut

    2012-09-01

    β-Human chorionic gonadotropin (βhCG) assays are routinely used to test for pregnancy. However, βhCG may be elevated in conditions other than pregnancy. We describe a case of metastatic lung adenocarcinoma presenting with a pathologic femur fracture and a false-positive urine pregnancy test. Lung cancer is the most common nongestational malignancy that produces βhCG among reproductive-age women. Emergency physicians should consider this rare cause of a positive pregnancy test result in women who deny recent sexual intercourse, especially if the patient is older than 40 years, has a history of tobacco use, or presents with respiratory complaints. PMID:22424649

  2. MicroRNA-126 inhibits invasion in non-small cell lung carcinoma cell lines

    SciTech Connect

    Crawford, M.; Brawner, E.; Batte, K.; Yu, L.; Hunter, M.G.; Otterson, G.A.; Nuovo, G.; Marsh, C.B.; Nana-Sinkam, S.P.

    2008-09-05

    Crk is a member of a family of adaptor proteins that are involved in intracellular signal pathways altering cell adhesion, proliferation, and migration. Increased expression of Crk has been described in lung cancer and associated with increased tumor invasiveness. MicroRNAs (miRNAs) are a family of small non-coding RNAs (approximately 21-25 nt long) that are capable of targeting genes for either degradation of mRNA or inhibition of translation. Crk is a predicted putative target gene for miR-126. Over-expression of miR126 in a lung cancer cell line resulted in a decrease in Crk protein without any alteration in the associated mRNA. These lung cancer cells exhibit a decrease in adhesion, migration, and invasion. Decreased cancer cell invasion was also evident following targeted knockdown of Crk. MiR-126 alters lung cancer cell phenotype by inhibiting adhesion, migration, and invasion and the effects on invasion may be partially mediated through Crk regulation.

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

    PubMed Central

    Zheng, Xiujuan; Hai, Wangxi; Chen, Kewei; Huang, Qiu; Xu, Yuhong; Peng, Jinliang

    2015-01-01

    Background [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. Methods 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. Results Values of SUVmax showed significant difference in subcutaneous tumor and inflammation (p<0.01), and in inflammations from different locations (p<0.005). However, SUVmax showed no statistical difference between in situ tumor and inflammation (p = 1.0) and among tumors from different locations (subcutaneous and in situ, p = 0.91). Values of Ki calculated from compartmental modeling showed significant difference between tumor and inflammation both subcutaneously (p<0.005) and orthotopically (p<0.01). Ki showed also location specific values for inflammations (subcutaneous, in situ and spontaneous, p<0.015). However, Ki of tumors from different locations (subcutaneous and in situ) showed no significant difference (p = 0.46). Conclusion In contrast to static PET based SUVmax, both subcutaneous and in situ inflammations and malignancies can be differentiated via dynamic FDG

  4. SU-F-BRD-10: Lung IMRT Planning Using Standardized Beam Bouquet Templates

    SciTech Connect

    Yuan, L; Wu, Q J.; Yin, F; Ge, Y

    2014-06-15

    Purpose: We investigate the feasibility of choosing from a small set of standardized templates of beam bouquets (i.e., entire beam configuration settings) for lung IMRT planning to improve planning efficiency and quality consistency, and also to facilitate automated planning. Methods: A set of beam bouquet templates is determined by learning from the beam angle settings in 60 clinical lung IMRT plans. A k-medoids cluster analysis method is used to classify the beam angle configuration into clusters. The value of the average silhouette width is used to determine the ideal number of clusters. The beam arrangements in each medoid of the resulting clusters are taken as the standardized beam bouquet for the cluster, with the corresponding case taken as the reference case. The resulting set of beam bouquet templates was used to re-plan 20 cases randomly selected from the database and the dosimetric quality of the plans was evaluated against the corresponding clinical plans by a paired t-test. The template for each test case was manually selected by a planner based on the match between the test and reference cases. Results: The dosimetric parameters (mean±S.D. in percentage of prescription dose) of the plans using 6 beam bouquet templates and those of the clinical plans, respectively, and the p-values (in parenthesis) are: lung Dmean: 18.8±7.0, 19.2±7.0 (0.28), esophagus Dmean: 32.0±16.3, 34.4±17.9 (0.01), heart Dmean: 19.2±16.5, 19.4±16.6 (0.74), spinal cord D2%: 47.7±18.8, 52.0±20.3 (0.01), PTV dose homogeneity (D2%-D99%): 17.1±15.4, 20.7±12.2 (0.03).The esophagus Dmean, cord D02 and PTV dose homogeneity are statistically better in the plans using the standardized templates, but the improvements (<5%) may not be clinically significant. The other dosimetric parameters are not statistically different. Conclusion: It's feasible to use a small number of standardized beam bouquet templates (e.g. 6) to generate plans with quality comparable to that of clinical

  5. Incomplete radiofrequency ablation accelerates proliferation and angiogenesis of residual lung carcinomas via HSP70/HIF-1α

    PubMed Central

    Wan, Jun; Wu, Wei; Huang, Yunlong; Ge, Wei; Liu, Shandong

    2016-01-01

    Radiofrequency ablation (RFA) therapy has been proved effective and feasible for lung cancer. However, the molecular mechanisms of local lung cancer recurrence following RFA are poorly understood. The present study aimed to evaluate the ability of HSP70/HIF-1α to affect the proliferation and angiogenesis of non-small cell lung cancers (NSCLCs) following insufficient RFA to uncover the molecular mechanisms of local recurrence. In vitro heat treatment was used to establish sublines of NCI-H1650 cells. The NCI-H1650 subline that was established by heat treatment at 54°C had a relatively higher viability and significantly elevated heat tolerance (compared to the parental strain). After treatment with the HSP70 inhibitor VER-155008, the HIF-1α inhibitor YC-1 and PI3K/Akt inhibitor wortmannin, the viability and proliferation rate of the cells was measured. At the same time, HSP70, HIF-1α and Akt were detected by real-time PCR and western blotting. In vivo xenograft tumors were created by subcutaneously inoculating nude mice with NCI-H1650 cells. HSP70, HIF-1α and Akt were detected by western blotting, and CD34 expression was detected by immunohistochemistry before and after RFA or treatment with the VER-155008, YC-1 or wortmannin inhibitors. The heat-adapted NCI-H1650 subline established in vitro had a higher viability and proliferative activity compared to parental cells. Inhibiting HSP70/HIF-1α abolished this difference. Blocking the PI3K/Akt signaling pathway decreased HSP70/HIF-1α expression levels. In vivo, we found that incomplete RFA treatment promoted HSP70/HIF-1α and CD34 expression. Additionally, the combination of RFA and treatment targeting HSP70/HIF-1α resulted in a synergistic reduction in tumor growth compared to incomplete RFA alone. The PI3K/Akt signaling pathway is also involved in regulating HSP70/HIF-1α expression during this process. We conclude that the accelerated proliferation and angiogenesis potential of residual lung carcinomas

  6. Incomplete radiofrequency ablation accelerates proliferation and angiogenesis of residual lung carcinomas via HSP70/HIF-1α.

    PubMed

    Wan, Jun; Wu, Wei; Huang, Yunlong; Ge, Wei; Liu, Shandong

    2016-08-01

    Radiofrequency ablation (RFA) therapy has been proved effective and feasible for lung cancer. However, the molecular mechanisms of local lung cancer recurrence following RFA are poorly understood. The present study aimed to evaluate the ability of HSP70/HIF-1α to affect the proliferation and angiogenesis of non-small cell lung cancers (NSCLCs) following insufficient RFA to uncover the molecular mechanisms of local recurrence. In vitro heat treatment was used to establish sublines of NCI-H1650 cells. The NCI-H1650 subline that was established by heat treatment at 54˚C had a relatively higher viability and significantly elevated heat tolerance (compared to the parental strain). After treatment with the HSP70 inhibitor VER-155008, the HIF-1α inhibitor YC-1 and PI3K/Akt inhibitor wortmannin, the viability and proliferation rate of the cells was measured. At the same time, HSP70, HIF-1α and Akt were detected by real-time PCR and western blotting. In vivo xenograft tumors were created by subcutaneously inoculating nude mice with NCI-H1650 cells. HSP70, HIF-1α and Akt were detected by western blotting, and CD34 expression was detected by immunohistochemistry before and after RFA or treatment with the VER-155008, YC-1 or wortmannin inhibitors. The heat-adapted NCI-H1650 subline established in vitro had a higher viability and proliferative activity compared to parental cells. Inhibiting HSP70/HIF-1α abolished this difference. Blocking the PI3K/Akt signaling pathway decreased HSP70/HIF-1α expression levels. In vivo, we found that incomplete RFA treatment promoted HSP70/HIF-1α and CD34 expression. Additionally, the combination of RFA and treatment targeting HSP70/HIF-1α resulted in a synergistic reduction in tumor growth compared to incomplete RFA alone. The PI3K/Akt signaling pathway is also involved in regulating HSP70/HIF-1α expression during this process. We conclude that the accelerated proliferation and angiogenesis potential of residual lung carcinomas

  7. Correlation of immunohistochemical staining p63 and TTF-1 with EGFR and K-ras mutational spectrum and diagnostic reproducibility in non small cell lung carcinoma.

    PubMed

    Thunnissen, Erik; Boers, Evan; Heideman, Daniëlle A M; Grünberg, Katrien; Kuik, Dirk J; Noorduin, Arnold; van Oosterhout, Matthijs; Pronk, Divera; Seldenrijk, Cees; Sietsma, Hannie; Smit, Egbert F; van Suylen, Robertjan; von der Thusen, Jan; Vrugt, Bart; Wiersma, Anne; Witte, Birgit I; den Bakker, Michael

    2012-12-01

    For treatment purposes, distinction between squamous cell carcinoma and adenocarcinoma is important. The aim of this study is to examine the diagnostic accuracy on lung cancer small biopsies for the distinction between adenocarcinoma and squamous cell carcinoma and relate these to immunohistochemical and KRAS and EGFR mutation analysis. An interobserver study was performed on 110 prospectively collected biopsies obtained by bronchoscopy or transthoracic needle biopsy of patients with non-small cell lung cancer. The diagnosis was correlated with immunohistochemical (IHC) analysis for markers of adeno- (TTF1 and/or mucin positivity) and squamous cell differentiation (P63 and CK5/6) as well as KRAS and EGFR mutation analysis. Eleven observers independently read H&E-stained slides of 110 cases, resulting in a kappa value of 0.55 ± 0.10. The diagnosis non-small cell lung cancer not otherwise specified was given on average on 29.5 % of the biopsies. A high concordance was observed between hematoxylin-eosin-based consensus diagnosis (≥8/11 readings concordant) and IHC markers. In all cases with EGFR (n = 1) and KRAS (n = 20) mutations, adenodifferentiation as determined by IHC was present and p63 staining was absent. In 2 of 25 cases with a consensus diagnosis of squamous cell carcinoma, additional stainings favored adenodifferentation, and a KRAS mutation was present. P63 is most useful for distinction between EGFR/KRAS mutation positive and negative patients. In the diagnostic work-up of non-small cell lung carcinoma the limited reproducibility on small biopsies is optimized with immunohistochemical analysis, resulting in reliable delineation for predictive analysis. PMID:23064619

  8. Assessment of DNA damage of Lewis lung carcinoma cells irradiated by carbon ions and X-rays using alkaline comet assay

    NASA Astrophysics Data System (ADS)

    Li, Ping; Zhou, Li-Bin; Jin, Xiao-Dong; He, Jing; Dai, Zhong-Ying; Zhou, Guang-Ming; Gao, Qing-Xiang; Li, Sha; Li, Qiang

    2008-01-01

    DNA damage and cell reproductive death determined by alkaline comet and clonogenic survival assays were examined in Lewis lung carcinoma cells after exposure to 89.63 MeV/u carbon ion and 6 MV X-ray irradiations, respectively. Based on the survival data, Lewis lung carcinoma cells were verified to be more radiosensitive to the carbon ion beam than to the X-ray irradiation. The relative biological effectiveness (RBE) value, which was up to 1.77 at 10% survival level, showed that the DNA damage induced by the high-LET carbon ion beam was more remarkable than that induced by the low-LET X-ray irradiation. The dose response curves of “Tail DNA (%)” (TD) and “Olive tail moment” (OTM) for the carbon ion irradiation showed saturation beyond about 8 Gy. This behavior was not found in the X-ray curves. Additionally, the carbon ion beam produced a lower survival fraction at 2 Gy (SF2) value and a higher initial Olive tail moment 2 Gy (OTM2) than those for the X-ray irradiation. These results suggest that carbon ion beams having high-LET values produced more severe cell reproductive death and DNA damage in Lewis lung carcinoma cells in comparison with X-rays and comet assay might be an effective predictive test even combining with clonogenic assay to assess cellular radiosensitivity.

  9. A Case of Lung Squamous Cell Carcinoma With Duodenal Metastasis on FDG PET/CT.

    PubMed

    Cheng, Gang

    2016-08-01

    Non-small cell lung cancer (NSCLC) tends to have distant metastasis. However, metastasis from NSCLC to the small bowel is uncommon, and duodenal metastasis from NSCLC is extremely rare. FDG PET/CT findings of duodenal metastasis from NSCLC have not been reported in the literature. In this case, we report FDG PET/CT findings in a 61-year-old NSCLC patient with biopsy-proven metastasis in the transverse duodenum. PMID:27055139

  10. Trace element profiles in murine Lewis lung carcinoma by radioisotope-induced X-ray fluorescence.

    PubMed Central

    Frank, A. S.; Schauble, M. K.; Preiss, I. L.

    1986-01-01

    Trace element profiles of various body tissues and tumor were established during growth of the Lewis lung tumor (LLT) with the use of radioisotope-induced X-ray fluorescence (RIXRF) analysis. The LLT, a highly malignant experimental murine tumor, resembles its human counterpart, has a well-defined life cycle, and kills its host in 30 days. When compared with normal controls, Zn, Br, and Rb levels in lung, liver, and skeletal muscle and Zn and Sr levels in bone from tumor-bearing mice exhibited large fluctuations at critical points in the tumor life cycle. In addition, the 24-day primary tumor trace element profile resembled that of its tissue of origin, normal lung, and was quite different from other normal tissues studied. These findings indicate that trace element profiles may help in the diagnosis, staging, and monitoring of disease. RIXRF is an excellent technique for this purpose because it is sensitive and relatively nondestructive of samples and has multielement capabilities. Images Figure 1 p423-a PMID:3953767

  11. Functional expression of choline transporter-like protein 1 (CTL1) in small cell lung carcinoma cells: a target molecule for lung cancer therapy.

    PubMed

    Inazu, Masato; Yamada, Tomoko; Kubota, Nobuo; Yamanaka, Tsuyoshi

    2013-10-01

    Choline is essential for the synthesis of the major membrane phospholipid phosphatidylcholine and the neurotransmitter acetylcholine (ACh). Elevated levels of choline and up-regulated choline kinase activity have been detected in cancer cells. Thus, the intracellular accumulation of choline through choline transporters is the rate-limiting step in phospholipid metabolism and a prerequisite for cancer cell proliferation. However, the uptake system for choline and the functional expression of choline transporters in lung cancer cells are poorly understood. We examined the molecular and functional characterization of choline uptake in the small cell lung carcinoma cell line NCI-H69. Choline uptake was saturable and mediated by a single transport system. Interestingly, removal of Na(+) from the uptake buffer strongly enhanced choline uptake. This increase in choline uptake under the Na(+)-free conditions was inhibited by dimethylamiloride (DMA), a Na(+)/H(+) exchanger (NHE) inhibitor. Various organic cations and the choline analog hemicholinium-3 (HC-3) inhibited the choline uptake and cell viability. A correlation analysis of the potencies of organic cations for the inhibition of choline uptake and cell viability showed a strong correlation (R=0.8077). RT-PCR revealed that choline transporter-like protein 1 (CTL1) mRNA and NHE1 are mainly expressed. HC-3 and CTL1 siRNA inhibited choline uptake and cell viability, and increased caspase-3/7 activity. The conversion of choline to ACh was confirmed, and this conversion was enhanced under Na(+)-free conditions, which in turn was sensitive to HC-3. These results indicate that choline uptake through CTL1 is used for ACh synthesis. Both an acetylcholinesterase inhibitor (eserine) and a butyrylcholinesterase inhibitor (ethopropazine) increased cell proliferation, and these effects were inhibited by 4-DAMP, a mAChR3 antagonist. We conclude that NCI-H69 cells express the choline transporter CTL1 which uses a directed H

  12. Long-term survival of a patient with small cell carcinoma of the stomach with metachronous lung metastases treated by multimodal therapy: a case report.

    PubMed

    Aoyagi, Keishiro; Kizaki, Junya; Isobe, Taro; Akagi, Yoshito

    2015-12-01

    A 69-year-old man was referred to our institution for treatment of gastric cancer. Type 2 gastric cancer was found on the anterior wall of the lower body of the stomach.The patient underwent distal gastrectomy, D2 lymph node dissection, and Roux-en-Y reconstruction with curative resection. The tumor was diagnosed as a small cell carcinoma of the stomach. Recurrence occurred in the lung after surgery. The patient underwent several chemoradiation therapy regimens, including cisplatin + irinotecan + radiation, S-1 + paclitaxel, amrubicin, carboplatin + etoposide, nogitecan, and docetaxel for lung metastases and radiation for brain and bone metastases for 43 months. He finally died of brain metastases 74 months after surgery (47 months after recognition of the lung metastases). Long continuous multimodal treatment including surgery, regimens for small cell lung cancer, S-1, taxanes, and radiation was thought to prolong the survival of this man with small cell carcinoma of the stomach. PMID:26943449

  13. Down-Regulation of Canonical and Up-Regulation of Non-Canonical Wnt Signalling in the Carcinogenic Process of Squamous Cell Lung Carcinoma

    PubMed Central

    Weich, Alexander; Kiss, Edit; Barko, Szilvia; Kovacs, Tamas; Avdicevic, Monika; D’Souza, Vijay K.; Rapp, Judit; Kvell, Krisztian; Jakab, Laszlo; Nyitrai, Miklos; Molnar, Tamas F.; Thickett, David R.; Laszlo, Terezia; Pongracz, Judit E.

    2013-01-01

    The majority of lung cancers (LC) belong to the non-small cell lung carcinoma (NSCLC) type. The two main NSCLC sub-types, namely adenocarcinoma (AC) and squamous cell carcinoma (SCC), respond differently to therapy. Whereas the link between cigarette smoke and lung cancer risk is well established, the relevance of non-canonical Wnt pathway up-regulation detected in SCC remains poorly understood. The present study was undertaken to investigate further the molecular events in canonical and non-canonical Wnt signalling during SCC development. A total of 20 SCC and AC samples with matched non-cancerous controls were obtained after surgery. TaqMan array analysis confirmed up-regulation of non-canonical Wnt5a and Wnt11 and identified down-regulation of canonical Wnt signalling in SCC samples. The molecular changes were tested in primary small airway epithelial cells (SAEC) and various lung cancer cell lines (e.g. A549, H157, etc). Our studies identified Wnt11 and Wnt5a as regulators of cadherin expression and potentiated relocation of β-catenin to the nucleus as an important step in decreased cellular adhesion. The presented data identifies additional details in the regulation of SCC that can aid identification of therapeutic drug targets in the future. PMID:23505429

  14. Nrf2-heme oxygenase-1 axis in mucoepidermoid carcinoma of the lung: Antitumoral effects associated with down-regulation of matrix metalloproteinases.

    PubMed

    Tertil, Magdalena; Golda, Slawomir; Skrzypek, Klaudia; Florczyk, Urszula; Weglarczyk, Kazimierz; Kotlinowski, Jerzy; Maleszewska, Monika; Czauderna, Szymon; Pichon, Chantal; Kieda, Claudine; Jozkowicz, Alicja; Dulak, Jozef

    2015-12-01

    Lung mucoepidermoid carcinoma (MEC) is a very poorly characterized rare subtype of non-small-cell lung cancer (NSCLC) associated with more favorable prognoses than other forms of intrathoracic malignancies. We have previously identified that heme oxygenase-1 (HO-1, encoded by HMOX1) inhibits MEC tumor growth and modulates the transcriptome of microRNAs. Here we investigate the role of a major upstream regulator of HO-1 and a master regulator of cellular antioxidant responses, transcription factor Nrf2, in MEC biology. Nrf2 overexpression in the NCI-H292 MEC cell line mimicked the phenotype of HO-1 overexpressing cells, leading to inhibition of cell proliferation and migration and down-regulation of oncogenic miR-378. HMOX1 silencing identified HO-1 as a major mediator of Nrf2 action. Nrf2- and HO-1 overexpressing cells exhibited strongly diminished expression of multiple matrix metalloproteinases and inflammatory cytokine interleukin-1β, which was confirmed in an NCI-HO-1 xenograft model. Overexpression of HO-1 altered not only human MMP levels in tumor cells but also murine MMP levels within tumor microenvironment and metastatic niche. This could possibly contribute to decreased metastasis to the lungs and inhibitory effects of HO-1 on MEC tumor growth. Our profound transcriptome analysis and molecular characterization of the mucoepidermoid lung carcinoma helps to understand the specific clinical presentations of these tumors, emphasizing a unique antitumoral role of the Nrf2-HO-1 axis. PMID:26393425

  15. Whole Exome Sequencing Identifies Frequent Somatic Mutations in Cell-Cell Adhesion Genes in Chinese Patients with Lung Squamous Cell Carcinoma.

    PubMed

    Li, Chenguang; Gao, Zhibo; Li, Fei; Li, Xiangchun; Sun, Yihua; Wang, Mengyun; Li, Dan; Wang, Rui; Li, Fuming; Fang, Rong; Pan, Yunjian; Luo, Xiaoyang; He, Jing; Zheng, Liangtao; Xia, Jufeng; Qiu, Lixin; He, Jun; Ye, Ting; Zhang, Ruoxin; He, Minghui; Zhu, Meiling; Hu, Haichuan; Shi, Tingyan; Zhou, Xiaoyan; Sun, Menghong; Tian, Shilin; Zhou, Yong; Wang, Qiaoxiu; Chen, Longyun; Yin, Guangliang; Lu, Jingya; Wu, Renhua; Guo, Guangwu; Li, Yingrui; Hu, Xueda; Li, Lin; Asan; Wang, Qin; Yin, Ye; Feng, Qiang; Wang, Bin; Wang, Hang; Wang, Mingbang; Yang, Xiaonan; Zhang, Xiuqing; Yang, Huanming; Jin, Li; Wang, Cun-Yu; Ji, Hongbin; Chen, Haiquan; Wang, Jun; Wei, Qingyi

    2015-01-01

    Lung squamous cell carcinoma (SQCC) accounts for about 30% of all lung cancer cases. Understanding of mutational landscape for this subtype of lung cancer in Chinese patients is currently limited. We performed whole exome sequencing in samples from 100 patients with lung SQCCs to search for somatic mutations and the subsequent target capture sequencing in another 98 samples for validation. We identified 20 significantly mutated genes, including TP53, CDH10, NFE2L2 and PTEN. Pathways with frequently mutated genes included those of cell-cell adhesion/Wnt/Hippo in 76%, oxidative stress response in 21%, and phosphatidylinositol-3-OH kinase in 36% of the tested tumor samples. Mutations of Chromatin regulatory factor genes were identified at a lower frequency. In functional assays, we observed that knockdown of CDH10 promoted cell proliferation, soft-agar colony formation, cell migration and cell invasion, and overexpression of CDH10 inhibited cell proliferation. This mutational landscape of lung SQCC in Chinese patients improves our current understanding of lung carcinogenesis, early diagnosis and personalized therapy. PMID:26503331

  16. Diffuse cystic lung disease due to pulmonary metastasis of colorectal carcinoma

    PubMed Central

    Fielli, Mariano; Avila, Fabio; Saino, Agustina; Seimah, Deborah; Fernández Casares, Marcelo

    2016-01-01

    The diffuse cystic lung diseases (DCLDs) are a pathophysiologically heterogeneous processes characterized by the presence of multiple thin-walled, air-filled spaces within the pulmonary parenchyma. The most common causes of DCLD are lymphangioleiomyomatosis (LAM) and pulmonary Langerhans cell histiocytosis (PLCH). DCLD develops rarely as a result of malignancy, typically secondary to metastases from peripheral sarcomas and mesenchymal tumors. DCLD have also been reported in a variety of other metastatic disease such as adenocarcinoma. Our case describes a patient with DCLD as a result of metastatic colorectal adenocarcinoma. PMID:27222791

  17. Diffuse cystic lung disease due to pulmonary metastasis of colorectal carcinoma.

    PubMed

    Fielli, Mariano; Avila, Fabio; Saino, Agustina; Seimah, Deborah; Fernández Casares, Marcelo

    2016-01-01

    The diffuse cystic lung diseases (DCLDs) are a pathophysiologically heterogeneous processes characterized by the presence of multiple thin-walled, air-filled spaces within the pulmonary parenchyma. The most common causes of DCLD are lymphangioleiomyomatosis (LAM) and pulmonary Langerhans cell histiocytosis (PLCH). DCLD develops rarely as a result of malignancy, typically secondary to metastases from peripheral sarcomas and mesenchymal tumors. DCLD have also been reported in a variety of other metastatic disease such as adenocarcinoma. Our case describes a patient with DCLD as a result of metastatic colorectal adenocarcinoma. PMID:27222791

  18. Chromogenic in situ hybridization to detect EGFR gene copy number in cell blocks from fine-needle aspirates of non small cell lung carcinomas and lung metastases from colo-rectal cancer

    PubMed Central

    2010-01-01

    Background Several studies demonstrated that epidermal growth factor receptor (EGFR) gene copy number (GCN) correlates to the response to tyrosine kinase inhibitors in non small cell lung cancer (NSCLC) and to anti-EGFR monoclonal antibodies (MoAbs) in metastatic colorectal cancer (CRC). In the presence of lung nodules, cytology is often the only possible diagnostic approach. Chromogenic in situ hybridization (CISH) is an alternative technique to fluorescence in situ hybridization (FISH), but its feasibility in detecting EGFR GCN in cell blocks from fine-needle aspiration cytology (FNAC) of lung nodules has not yet been established. Methods We evaluated the feasibility of CISH on 33 FNAC from 20 primary NSCLC (5 squamous carcinomas, 8 large cell carcinomas and 7 adenocarcinomas) and 13 lung metastases from CRC. Results Of the 33 FNAC analyzed by CISH, 27 (82%) presented a balanced increase in EGFR gene and chromosome 7 number: 10 cases (30%) showed a low polysomy, 15 (45%) a high polysomy and 2 (6%) NSCLC were amplified. No significant differences between NSCLC and CRC lung metastases were found in relation to disomic or polysomic status. In addition, no correlation between EGFR GCN and EGFR immunohistochemical overexpression was found. Furthermore, we compared CISH results with those obtained by FISH on the same samples and we found 97% overall agreement between the two assays (k = 0.78, p < 0.0001). Two cases were amplified with both assays, whereas 1 case of NSCLC was amplified by FISH only. CISH sensitivity was 67%, the specificity and positive predictive value (PPV) was 100%, and the negative predictive value (NPV) was 97%. Conclusions Our study shows that CISH is a valid method to detect EGFR GCN in cell blocks from FNAC of primary NSCLC or metastatic CRC to the lung. PMID:20843314

  19. Mesenchymal Stem Cells Shed Amphiregulin at the Surface of Lung Carcinoma Cells in a Juxtacrine Manner12

    PubMed Central

    Carnet, Oriane; Lecomte, Julie; Masset, Anne; Primac, Irina; Durré, Tania; Maertens, Ludovic; Detry, Benoit; Blacher, Silvia; Gilles, Christine; Péqueux, Christel; Paupert, Jenny; Foidart, Jean-Michel; Jerusalem, Guy; Cataldo, Didier; Noel, Agnès

    2015-01-01

    Solid tumors comprise cancer cells and different supportive stromal cells, including mesenchymal stem cells (MSCs), which have recently been shown to enhance tumor growth and metastasis. We provide new mechanistic insights into how bone marrow (BM)–derived MSCs co-injected with Lewis lung carcinoma cells promote tumor growth and metastasis in mice. The proinvasive effect of BM-MSCs exerted on tumor cells relies on an unprecedented juxtacrine action of BM-MSC, leading to the trans-shedding of amphiregulin (AREG) from the tumor cell membrane by tumor necrosis factor-α–converting enzyme carried by the BM-MSC plasma membrane. The released soluble AREG activates cancer cells and promotes their invasiveness. This novel concept is supported by the exploitation of different 2D and 3D culture systems and by pharmacological approaches using a tumor necrosis factor-α–converting enzyme inhibitor and AREG-blocking antibodies. Altogether, we here assign a new function to BM-MSC in tumor progression and establish an uncovered link between AREG and BM-MSC. PMID:26297433

  20. Efficacy of treatment of colon, lung and breast human carcinoma xenografts with: doxorubicin, cisplatin, irinotecan or topotecan.

    PubMed

    Hardman, W E; Moyer, M P; Cameron, I L

    1999-01-01

    Given that human cancer xenografts tend to retain chemosensitivities similar to the cancerous tissue of origin, human carcinoma xenografts grown in nude mice were tested for sensitivity to four drug protocols: doxorubicin at 5 mg/kg, i.v., q5d; irinotecan at 60 mg/kg, i.v., q4d; cisplatin 5 mg/kg, i.p., q7d; and topotecan 1.5 mg/kg, p.o., qd (5 of 7 days). Irinotecan and doxorubicin protocols either halted or caused significant regression of the breast cancer cell lines (MCF7, MDA-MB 231 and T47D). None of the protocols tested resulted in significant regression in the lung cancer xenografts (H460, A549 and H226) although both irinotecan and doxorubicin did halt growth of the H226 xenograft. The ability of the irinotecan treatment to cause regression of xenograft size in all three colon cancer cell lines (SW620, COLO205 and HT29) justifies further clinical trials of irinotecan as an especially promising drug for the treatment of colon cancer. PMID:10472342

  1. Identification and Characterization of Epstein-Barr Virus Genomes in Lung Carcinoma Biopsy Samples by Next-Generation Sequencing Technology

    PubMed Central

    Wang, Shanshan; Xiong, Hongchao; Yan, Shi; Wu, Nan; Lu, Zheming

    2016-01-01

    Epstein-Barr virus (EBV) has been detected in the tumor cells of several cancers, including some cases of lung carcinoma (LC). However, the genomic characteristics and diversity of EBV strains associated with LC are poorly understood. In this study, we sequenced the EBV genomes isolated from four primary LC tumor biopsy samples, designated LC1 to LC4. Comparative analysis demonstrated that LC strains were more closely related to GD1 strain. Compared to GD1 reference genome, a total of 520 variations in all, including 498 substitutions, 12 insertions, and 10 deletions were found. Latent genes were found to harbor the most numbers of nonsynonymous mutations. Phylogenetic analysis showed that all LC strains were closely related to Asian EBV strains, whereas different from African/American strains. LC2 genome was distinct from the other three LC genomes, suggesting at least two parental lineages of EBV among the LC genomes may exist. All LC strains could be classified as China 1 and V-val subtype according to the amino acid sequence of LMP1 and EBNA1, respectively. In conclusion, our results showed the genomic diversity among EBV genomes isolated from LC, which might facilitate to uncover the previously unknown variations of pathogenic significance. PMID:27189712

  2. Paraneoplastic Choreoathetosis in a Patient with Small Cell Lung Carcinoma and Anti-CRMP5/CV2: A Case Report

    PubMed Central

    Aydin, Dogu; Somnier, Finn; Lassen, Lisbeth H.

    2016-01-01

    Introduction The occurrence of more or less monosymptomatic paraneoplastic choreoathetosis associated with anti-CRMP5/CV2 antibodies is rare. Typically, such autoantibodies are associated with a more classical syndrome – paraneoplastic encephalomyelitis. Frequently, small cell lung carcinoma (SCLC) is the related neoplastic finding. Case Report We present a 71-year-old woman who developed visual symptoms with papilledema and chorea. Anti-CRMP5/CV2 antibodies were a feature of both the serum and cerebrospinal fluid. Although SCLC was suspected already at the time of the initial examinations, no signs of primary or metastatic tumors were revealed on chest X-ray, MRI or whole-body PET scan. EEG and bronchoscopy were also unremarkable. However, 6 months after the onset, a repeated PET scan and subsequent bronchoscopic biopsy revealed SCLC. In spite of chemotherapy, the SCLC progressed, and the patient died 14 months after the onset of the symptoms. Conclusion We report paraneoplastic choreoathetosis associated with anti-CRMP5/CV2 antibodies. Such published case histories are rare. Although expected, we did not find any reduced signal intensity at the basal ganglia on the T1-weighted or increased intensity on the T2-weighted MRI scans. PMID:26889151

  3. Differential permeability and quantitative MR imaging of a human lung carcinoma brain xenograft in the nude rat.

    PubMed Central

    Barnett, P. A.; Roman-Goldstein, S.; Ramsey, F.; McCormick, C. I.; Sexton, G.; Szumowski, J.; Neuwelt, E. A.

    1995-01-01

    This study characterized agent differential permeability, three-dimensional tumor volume, and survival in an LX-1 human small cell lung carcinoma intracerebral xenograft model in the nude rat. The percent accessible tissue space (distribution volume) and the permeability x capillary surface product for aminoisobutyric acid (M(r) 103), methotrexate (M(r) 454), dextran 10 (M(r) 10,000), and dextran 70 (M(r) 70,000) were measured between 8 and 16 days after inoculation of tumor. Magnetic resonance imaging and histology were used to quantitate intracerebral tumor volume (mm3). Accessible tissue space (ml/g) and permeability x capillary surface product in intracranial tumor, surrounding brain, and subcutaneous tumor decreased with increasing molecular weight of the agent, regardless of the number of days after inoculation. Accessible tissue space in intracranial tumor increased between 8 and 16 days for all agents except dextran 70. There was little change in the subcutaneous tumor or other tissues with time. Tumor volume calculations from imaging studies correlated with volumetric measurements from histological sections (r2 = 98.5%) and illustrated natural tumor progression (9 to 225 mm3). These results provide a basis for therapeutic design based on differential permeability of specific agents and the ability to quantitatively measure brain tumor volume for accessing tumor response. Images Figure 4 PMID:7856753

  4. Role of chest irradiation in limited small cell carcinoma of the lung treated with combination chemotherapy

    SciTech Connect

    Looper, J.D.; Hornback, N.B.

    1984-10-01

    Between October 1974 and December 1980, 123 patients with limited small cell carcinoma were treated in the Indiana University Medical Center Department of Radiation Oncology. Of these, 115 were treated with preplanned combined modality therapy using irradiation and polychemotherapy (Adriamycin, Cytoxan and Oncovin). All patients received whole brain prophylactic irradiation and were followed a minimum of 2 years. Sixty-six patients were given chest irradiation with all but two receiving 3500-4000 rad while 49 did not receive this treatment. Sixty-five percent of those patients receiving chest irradiation had a complete response to therapy, as opposed to 33% who did not. This study demonstrates an increase response rate, median survival, and overall survival in patients receiving chest irradiation. The high rate of relapse in the chest suggests the need for more effective control of the primary. This may be accomplished by increasing the dose of chest irradiation or surgical removal when feasible.

  5. Proteomic analysis of colon and rectal carcinoma using standard and customized databases

    PubMed Central

    Slebos, Robbert J.C.; Wang, Xia; Wang, Xaojing; Zhang, Bing; Tabb, David L.; Liebler, Daniel C.

    2015-01-01

    Understanding proteomic differences underlying the different phenotypic classes of colon and rectal carcinoma is important and may eventually lead to a better assessment of clinical behavior of these cancers. We here present a comprehensive description of the proteomic data obtained from 90 colon and rectal carcinomas previously subjected to genomic analysis by The Cancer Genome Atlas (TCGA). Here, the primary instrument files and derived secondary data files are compiled and presented in forms that will allow further analyses of the biology of colon and rectal carcinoma. We also discuss new challenges in processing these large proteomic datasets for relevant proteins and protein variants. PMID:26110064

  6. Radiation Therapy and MK-3475 for Patients With Recurrent/Metastatic Head and Neck Cancer, Renal Cell Cancer, Melanoma, and Lung Cancer

    ClinicalTrials.gov

    2016-07-06

    Head and Neck Squamous Cell Carcinoma; Metastatic Renal Cell Cancer; Recurrent Head and Neck Carcinoma; Recurrent Lung Carcinoma; Recurrent Renal Cell Carcinoma; Recurrent Skin Carcinoma; Stage III Renal Cell Cancer; Stage IV Lung Cancer; Stage IV Skin Melanoma

  7. Squamous Cell Lung Carcinoma Presenting With Refractory Status Epilepticus: A Case Report of Paraneoplastic Limbic Encephalitis.

    PubMed

    Hurley, Killian; Herron, Malcolm; McDermott, Sean; Farrell, Terence; O'Riordan, Deirdre

    2015-08-01

    Lung cancer-associated paraneoplastic syndromes affecting the central nervous system present significant diagnostic and treatment challenges. In this case, the patient presented with personality change, cognitive impairment, complex partial seizures, ataxia, dyspraxia, and dysphasia. Shortly after admission, the patient suffered refractory generalized tonic-clonic seizures and a decreased level of consciousness and required intubation, ventilation, and admission to the ICU. He was subsequently diagnosed with paraneoplastic limbic encephalitis based on recognized criteria, including a compatible clinical picture, elevated protein content in his cerebrospinal fluid with negative cytology, a positive positron emission tomography-computed tomography scan showing a right upper lobe tumor, and the exclusion of other neuro-oncological complications. Histopathology confirmed the tissue diagnosis as squamous cell cancer. Initial immunotherapy with steroids and intravenous immunoglobulin and subsequent lobectomy and adjuvant chemotherapy were partially successful, leading to partial resolution of his cognitive impairment. This report highlights the diagnostic and therapeutic challenges of lung-related paraneoplastic syndromes. In addition, it illustrates the poor outcomes for patients and identifies squamous cell cancer as an extremely rare cause of paraneoplastic limbic encephalitis. PMID:25784771

  8. Radix Tetrastigma hemsleyani flavone inhibits proliferation, migration, and invasion of human lung carcinoma A549 cells

    PubMed Central

    Zhong, Liangrui; Zheng, Junxian; Sun, Qianqian; Wei, Kemin; Hu, Yijuan

    2016-01-01

    Radix Tetrastigma hemsleyani flavone (RTHF) is widely used as a traditional herb and has detoxification and anti-inflammatory effects. In this study, we investigated the potential effects of RTHF on the growth and metastasis of human lung adenocarcinoma A549 cells and evaluated its mechanisms. A549 cells were treated with RTHF at various concentrations for different periods. In vitro Cell Counting Kit-8 assay and colony formation methods showed that RTHF had dose- and time-dependent antiproliferation effects on A549 cells. A cell adhesion assay showed that RTHF decreased A549 cell adhesion in a dose-dependent manner. Cell invasion and migration were investigated using the Transwell assay and observed using an inverted microscope; the results showed that cell metastasis was significantly lower in the treatment group than that in the control group (P<0.01). Expression of metastasis-related matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) was detected by real-time polymerase chain reaction and Western blotting. The results showed that the expression of MMP-2, MMP-9, and TIMP-1 decreased, while that of TIMP-2 increased significantly in the RTHF group when compared with the results of the control group. These results show that RTHF exhibits antigrowth and antimetastasis activity in lung cancer A549 cells by decreasing the expression of MMP-2/-9 and TIMP-1 and increasing that of TIMP-2. PMID:26893573

  9. Pituitary metastasis of lung neuroendocrine carcinoma: case report and literature review.

    PubMed

    de Siqueira, Pedro Freire; Mathez, Andréia Latanza Gomes; Pedretti, Denize Borges; Abucham, Julio

    2015-12-01

    Metastasis to the pituitary gland is an unusual situation in clinical practice, but the frequency thereof is increasing due to the increased survival of cancer patients, and greater availability of imaging. In most cases, they are found between the sixth and seventh decades of life, as determined in image examination of patients with known malignant neoplasm, but, generally, asymptomatic with respect to pituitary involvement. The most common primary sites are breast in women and lung in men. We present the case of a 64-year-old patient with clinical visual changes, polyuria, polydipsia, and decreased level of consciousness whose tests showed pan-hypopituitarism, hypernatremia and low urine specific gravity, and extensive mass in sellar region. Diabetes insipidus was confirmed and treated, corticotrophic and thyroid deficits were corrected and then the patient underwent resection by transsphenoidal surgery. The histopathological and immunohistochemistry analysis revealed pituitary metastasis of lung neuroendocrine tumor. Subsequently, a chest CT scan showed pulmonary mass consistent with primary neoplasm. Despite the water and electrolyte correction and intravenous glucocorticoid replacement, the patient continued to show decreased level of consciousness due to compression of the brain stem by the pituitary mass, evolving to death. The purpose is to call attention to the differential diagnosis of invasive lesions of the sellar region, mainly in individuals over 50 years and/or when associated with diabetes insipidus, as it may be a case of metastasis, although there is no known primary neoplasm. PMID:26677090

  10. Lung cancer: Biology and treatment options.

    PubMed

    Lemjabbar-Alaoui, Hassan; Hassan, Omer Ui; Yang, Yi-Wei; Buchanan, Petra

    2015-12-01

    Lung cancer remains the leading cause of cancer mortality in men and women in the U.S. and worldwide. About 90% of lung cancer cases are caused by smoking and the use of tobacco products. However, other factors such as radon gas, asbestos, air pollution exposures, and chronic infections can contribute to lung carcinogenesis. In addition, multiple inherited and acquired mechanisms of susceptibility to lung cancer have been proposed. Lung cancer is divided into two broad histologic classes, which grow and spread differently: small-cell lung carcinomas (SCLCs) and non-small cell lung carcinomas (NSCLCs). Treatment options for lung cancer include surgery, radiation therapy, chemotherapy, and targeted therapy. Therapeutic-modalities recommendations depend on several factors, including the type and stage of cancer. Despite the improvements in diagnosis and therapy made during the past 25 years, the prognosis for patients with lung cancer is still unsatisfactory. The responses to current standard therapies are poor except for the most localized cancers. However, a better understanding of the biology pertinent to these challenging malignancies, might lead to the development of more efficacious and perhaps more specific drugs. The purpose of this review is to summarize the recent developments in lung cancer biology and its therapeutic strategies, and discuss the latest treatment advances including therapies currently under clinical investigation. PMID:26297204

  11. Methoxyamine, Pemetrexed Disodium, Cisplatin, and Radiation Therapy in Treating Patients With Stage IIIA-IV Non-small Cell Lung Cancer

    ClinicalTrials.gov

    2016-04-05

    Metastatic Malignant Neoplasm in the Brain; Stage IIIA Large Cell Lung Carcinoma; Stage IIIA Lung Adenocarcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Large Cell Lung Carcinoma; Stage IIIB Lung Adenocarcinoma; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Large Cell Lung Carcinoma; Stage IV Lung Adenocarcinoma; Stage IV Non-Small Cell Lung Cancer

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

    PubMed Central

    Qian, Jun; Zou, Yong; Wang, Jing; Zhang, Bing; Massion, Pierre P.

    2015-01-01

    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. PMID:26484266

  13. Tumor-suppressive microRNA-29 family inhibits cancer cell migration and invasion directly targeting LOXL2 in lung squamous cell carcinoma.

    PubMed

    Mizuno, Keiko; Seki, Naohiko; Mataki, Hiroko; Matsushita, Ryosuke; Kamikawaji, Kazuto; Kumamoto, Tomohiro; Takagi, Koichi; Goto, Yusuke; Nishikawa, Rika; Kato, Mayuko; Enokida, Hideki; Nakagawa, Masayuki; Inoue, Hiromasa

    2016-02-01

    Lung cancer remains the most frequent cause of cancer-related death in developed countries. A recent molecular-targeted strategy has contributed to improvement of the remarkable effect of adenocarcinoma of the lung. However, such treatment has not been developed for squamous cell carcinoma (SCC) of the disease. Our recent studies of microRNA (miRNA) expression signatures of human cancers showed that the microRNA-29 family (miR‑29a, miR‑29b and miR‑29c) significantly reduced cancer tissues compared to normal tissues. These findings suggest that miR‑29s act as tumor-suppressors by targeting several oncogenic genes. The aim of the study was to investigate the functional significance of miR‑29s in lung SCC and to identify miR‑29s modulating molecular targets in lung SCC cells. Restoration of all mature members of the miR‑29s inhibited cancer cell migration and invasion. Gene expression data combined in silico analysis and luciferase reporter assays demonstrated that the lysyl oxidase-like 2 (LOXL2) gene was a direct regulator of tumor‑suppressive miR‑29s. Moreover, overexpressed LOXL2 was confirmed in lung SCC clinical specimens, and silencing of LOXL2 inhibited cancer cell migration and invasion in lung SCC cell lines. Our present data suggested that loss of tumor-suppressive miR‑29s enhanced cancer cell invasion in lung SCC through direct regulation of oncogenic LOXL2. Elucidation of the novel lung SCC molecular pathways and targets regulated by tumor-suppressive miR‑29s will provide new insights into the potential mechanisms of oncogenesis and metastasis of the disease. PMID:26676674

  14. Tumor-suppressive microRNA-29 family inhibits cancer cell migration and invasion directly targeting LOXL2 in lung squamous cell carcinoma

    PubMed Central

    MIZUNO, KEIKO; SEKI, NAOHIKO; MATAKI, HIROKO; MATSUSHITA, RYOSUKE; KAMIKAWAJI, KAZUTO; KUMAMOTO, TOMOHIRO; TAKAGI, KOICHI; GOTO, YUSUKE; NISHIKAWA, RIKA; KATO, MAYUKO; ENOKIDA, HIDEKI; NAKAGAWA, MASAYUKI; INOUE, HIROMASA

    2016-01-01

    Lung cancer remains the most frequent cause of cancer-related death in developed countries. A recent molecular-targeted strategy has contributed to improvement of the remarkable effect of adenocarcinoma of the lung. However, such treatment has not been developed for squamous cell carcinoma (SCC) of the disease. Our recent studies of microRNA (miRNA) expression signatures of human cancers showed that the microRNA-29 family (miR-29a, miR-29b and miR-29c) significantly reduced cancer tissues compared to normal tissues. These findings suggest that miR-29s act as tumor-suppressors by targeting several oncogenic genes. The aim of the study was to investigate the functional significance of miR-29s in lung SCC and to identify miR-29s modulating molecular targets in lung SCC cells. Restoration of all mature members of the miR-29s inhibited cancer cell migration and invasion. Gene expression data combined in silico analysis and luciferase reporter assays demonstrated that the lysyl oxidase-like 2 (LOXL2) gene was a direct regulator of tumor-suppressive miR-29s. Moreover, overexpressed LOXL2 was confirmed in lung SCC clinical specimens, and silencing of LOXL2 inhibited cancer cell migration and invasion in lung SCC cell lines. Our present data suggested that loss of tumor-suppressive miR-29s enhanced cancer cell invasion in lung SCC through direct regulation of oncogenic LOXL2. Elucidation of the novel lung SCC molecular pathways and targets regulated by tumor-suppressive miR-29s will provide new insights into the potential mechanisms of oncogenesis and metastasis of the disease. PMID:26676674

  15. Intravenous injection of siRNA directed against hypoxia-inducible factors prolongs survival in a Lewis lung carcinoma cancer model.

    PubMed

    Kamlah, F; Eul, B G; Li, S; Lang, N; Marsh, L M; Seeger, W; Grimminger, F; Rose, F; Hänze, J

    2009-03-01

    Different routes for the in vivo administration of synthetic siRNA complexes targeting lung tumors were compared, and siRNA complexes were administered for the inhibition of hypoxia-inducible factor (HIF-1alpha and HIF-2alpha). Intravenous jugular vein injection of siRNA proved to be the most effective means of targeting lung tumor tissue in the Lewis lung carcinoma (LLC1) model. In comparison, intraperitoneal injection of siRNA was not suitable for targeting of lung tumor and intratracheal administration of siRNA exclusively targeted macrophages. Inhibition of HIF-1alpha and HIF-2alpha by siRNA injected intravenously was validated by immunohistofluorescent analysis for glucose-transporter-1 (GLUT-1), a well-established HIF target protein. The GLUT-1 signal was strongly attenuated in the lung tumors of mice treated with siRNA-targeting HIF-1alpha and HIF-2alpha, compared with mice treated with control siRNA. Interestingly, injection of siRNA directed against HIF-1alpha and HIF-2alpha into LLC1 lung tumor-bearing mice resulted in prolonged survival. Immunohistological analysis of the lung tumors from mice treated with siRNA directed against HIF-1alpha and HIF-2alpha displayed reduced proliferation, angiogenesis and apoptosis, cellular responses, which are known to be affected by HIF. In conclusion, intravenous jugular vein injection of siRNA strongly targets the lung tumor and is effective in gene inhibition as demonstrated for HIF-1alpha and HIF-2alpha. PMID:18818708

  16. Mushroom β-Glucan May Immunomodulate the Tumor-Associated Macrophages in the Lewis Lung Carcinoma

    PubMed Central

    Wang, Wan-Jhen; Wu, Yu-Sheng; Chen, Sherwin; Liu, Chi-Feng; Chen, Shiu-Nan

    2015-01-01

    The present study showed that oral mushroom beta-glucan treatment significantly increased IFN-γ mRNA expression but significantly reduced COX-2 mRNA expression within the lung. For LLC tumor model, oral Ganoderma lucidum or Antrodia camphorata polysaccharides treatments significantly reduced TGF-β production in serum. In addition, IL-12 and IFN-γ mRNA expression were significantly increased, but IL-6, IL-10, COX-2, and TGF-β mRNA expression were substantially following oral mushroom polysaccharides treatments. The study highlights the efficacious effect of mushroom polysaccharides for ameliorating the immune suppression in the tumor microenvironment. Increased M1 phenotype of tumor-associated macrophages and attenuated M2 phenotype of tumor-associated macrophages could be achieved by ingesting mushroom polysaccharides. PMID:26167490

  17. The association between Lambert–Eaton myasthenic syndrome and small cell lung carcinoma

    PubMed Central

    Briggs, Sarah EW; Gozzard, Paul; Talbot, Denis C

    2013-01-01

    Lambert–Eaton myasthenic syndrome (LEMS) is an autoimmune disorder mediated by autoantibodies to voltage-gated calcium channels. The disorder is diagnosed clinically on the basis of a triad of symptoms (proximal muscle weakness, hyporeflexia, and autonomic disturbance), supported by electrophysiological findings and the presence of autoantibodies. Between 40% and 62% of patients diagnosed with LEMS are found to have small-cell lung cancer (SCLC), almost all of whom develop neurological symptoms before their cancer is diagnosed. Prompt identification of LEMS and appropriate screening for SCLC is key to improving the outcome of both conditions. Here we review the pathophysiology and clinical management of LEMS, focusing particularly on the relationship with SCLC.

  18. Differential Matrix Metalloproteinase Levels in Adenocarcinoma and Squamous Cell Carcinoma of the Lung

    PubMed Central

    Shah, Sonam A; Spinale, Francis G; Ikonomidis, John S; Stroud, Robert E; Chang, Eileen I; Reed, Carolyn E

    2010-01-01

    Objective The matrix metalloproteinases (MMPs) have been implicated in the aggressive course of non-small cell lung cancer (NSCLC). However, there are a large number of MMP subtypes with diverse proteolytic substrates and different induction pathways. This study tested the hypothesis that a differential MMP profile would exist between NSCLC and normal lung and that MMP patterns would differ between NSCLC histologic type. Methods NSCLC samples and remote normal samples were obtained from patients with stage I or II NSCLC with either squamous cell (n=22) or adenocarcinoma (n=19) histology. Absolute concentrations for each of the MMP subclasses; collagenases (MMP-1, 8, -13), gelatinases (MMP-2,-9), lysins (MMP-2, -7) and elastase (MMP-12) were determined by a calibrated and validated multiplex suspension array. Results Overall, MMP levels were significantly increased in NSCLC compared to normal. For example, MMP-1 and MMP-7 increased by approximately 10 fold in NSCLC (p<0.05). Moreover, a different MMP portfolio was observed between NSCLC histologic types. For example MMP-1,-8,-9 and -12 increased by over 4-fold in squamous cell versus adenocarcinoma (p<0.05). In those patients who recurred within 3 years of resection, 3-fold higher levels of MMP-8 and -9 were observed (p<0.05). Conclusion Increased levels of a number of MMP types occur with NSCLC, but the MMP profile was distinctly different between histologic types and in those patients with recurrence. These different MMP profiles may be important in the mechanistic basis for the natural history of different NSCLC types, as well as identifying potential prognostic and therapeutic targets. PMID:20304142

  19. Recommendations for reducing the effect of grain dust on the lungs. Canadian Thoracic Society Standards Committee.

    PubMed Central

    Becklake, M; Broder, I; Chan-Yeung, M; Dosman, J A; Ernst, P; Herbert, F A; Kennedy, S M; Warren, P W

    1996-01-01

    OBJECTIVE: To assess the appropriateness of the current Canadian standards for exposure to grain dust in the workplace. OPTIONS: The current permissible exposure limit of 10 mg of total grain dust per cubic metre of air (expressed as mg/m3) as an 8-hour time-weighted average exposure, or a lower permissible exposure limit. OUTCOMES: Acute symptoms of grain-dust exposure, such as cough, phlegm production, wheezing and dyspnea, similar chronic symptoms, and spirometric deficits revealing obstructive or restrictive disease. EVIDENCE: Articles published from 1924 to December 1993 were identified from Index Medicus and the bibliographies of pertinent articles. Subsequent articles published from 1994 (when the recommendations were approved by the Canadian Thoracic Society Standards Committee) to June 1996 were retrieved through a search of MEDLINE, and modification of the recommendations was not found to be necessary. Studies of interest were those that linked measurements of total grain dust levels to the development of acute and chronic respiratory symptoms and changes in lung function in exposed workers. Papers on the effects of grain dust on workers in feed mills were not included because other nutrients such as animal products may have been added to the grain. Unpublished reports (e.g., to Labour Canada) were included as sources of information. VALUES: A high value was placed on minimizing the biological harm that grain dust has on the lungs of grain workers. BENEFITS, HARMS AND COSTS: A permissible exposure limit of 5 mg/m3 would control the short-term effects of exposure to grain dust on workers. Evidence is insufficient to determine what level is needed to prevent long-term effects. The economic implications of implementing a lower permissible exposure limit have not been evaluated. RECOMMENDATIONS: The current Canadian standards for grain-dust exposure should be reviewed by Labour Canada and the grain industry. A permissible exposure level of 5 mg/m3 is

  20. Lung transplantation from donors outside standard acceptability criteria--are they really marginal?

    PubMed

    Zych, Bartlomiej; García Sáez, Diana; Sabashnikov, Anton; De Robertis, Fabio; Amrani, Mohamed; Bahrami, Toufan; Mohite, Prashant N; Patil, Nikhil P; Weymann, Alexander; Popov, Aron F; Reed, Anna; Carby, Martin; Simon, André R

    2014-11-01

    Lung transplantation (LTx) from "extended donor criteria" donors may reduce significantly organ shortage. However, its influence on results remains unclear. In this study, we evaluate retrospectively the results of LTx from donors outside standard criteria: PaO2/FiO2 ratio < 300 mmHg, age over 55 years, and history of smoking > 20 pack-years. Two hundred and forty-eight patients underwent first time LTx in our institution between January 2007 and January 2013. Seventy-nine patients (Group I) received organs from "extended donor criteria" and 169 patients (Group II) from "standard donor criteria." Recipients' and donors' demographics, perioperative variables, and outcome were compared. Donors from Group I were significantly older [median (interquartile range)]: 52.5 (44;58) vs. 42 (28.5;48.5) years (P < 0.001) with lower PaO2/FiO2 ratio: 366 ± 116.1 455 ± 80.5 mmHg (P < 0.001), higher incidence of smoking history: 57.7% vs. 41.8% (P = 0.013), and more extensive smoking history: 24(15;30) vs. 10(3.75;14) pack-years (P < 0.001). Other parameters were comparable. Recipients' gender, diagnosis, percentage of patients operated on pump and receiving double LTx were also comparable. Recipients from Group I were significantly older: 50 (42;57) vs. 44 (29.5;53.5) years (P = 001). There were no differences observed in recipients' prevalence of primary graft dysfunction (PGD) grade 3 over first three postoperative days, duration of mechanical ventilation, intensive care and hospital length of stay, prevalence of rejection, and bronchiolitis obliterans syndrome (BOS). 90-day, 1-year, and 5-year survival (Group I vs. II) were also similar: 88.6% vs. 91.7%, 83.2% vs. 84.6%, and 59% vs. 68.2% (log rank P = 0.367). Carefully selected donor lungs from outside the standard acceptability criteria may expand existing donor pool with no detrimental effect on LTx outcome. PMID:25070600

  1. Videothoracoscopic resection for lung cancer: moving towards a “standard of care”

    PubMed Central

    2016-01-01

    Videothoracic surgery for lung cancer is now an established practice but there is a division of opinion between surgeons whose aim is to spare all patients a thoracotomy and those who have not adopted videoscopic methods for routine lobectomy. The latter remain in the majority; most patients at present have a thoracotomy. Surgeons from Europe and America met in Catania, Sicily at the 3rd Mediterranean Symposium on Thoracic Surgical Oncology to explore the evidence and the routes to making videothoracoscopic surgery a standard of care. Evidence from one completed randomized controlled trial (RCT) and several propensity score matching studies indicate that less invasive surgery is at least as safe as thoracotomy. By the accepted standards of an oncological lobectomy which include clearance of the primary cancer and the intended lymphadenectomy or sampling, the operations are equivalent. Clinical effectiveness in achieving long-term cancer free survival is likely. However, the co-existance of videothoracoscopy has encouraged smaller non-muscle cutting incisions and the avoidance of rib spreading, narrowing whatever gap there may have been in terms of the patients’ experience. PMID:27621911

  2. Videothoracoscopic resection for lung cancer: moving towards a "standard of care".

    PubMed

    Treasure, Tom

    2016-08-01

    Videothoracic surgery for lung cancer is now an established practice but there is a division of opinion between surgeons whose aim is to spare all patients a thoracotomy and those who have not adopted videoscopic methods for routine lobectomy. The latter remain in the majority; most patients at present have a thoracotomy. Surgeons from Europe and America met in Catania, Sicily at the 3(rd) Mediterranean Symposium on Thoracic Surgical Oncology to explore the evidence and the routes to making videothoracoscopic surgery a standard of care. Evidence from one completed randomized controlled trial (RCT) and several propensity score matching studies indicate that less invasive surgery is at least as safe as thoracotomy. By the accepted standards of an oncological lobectomy which include clearance of the primary cancer and the intended lymphadenectomy or sampling, the operations are equivalent. Clinical effectiveness in achieving long-term cancer free survival is likely. However, the co-existance of videothoracoscopy has encouraged smaller non-muscle cutting incisions and the avoidance of rib spreading, narrowing whatever gap there may have been in terms of the patients' experience. PMID:27621911

  3. p53 gene product expression in resected non-small cell carcinoma of the lung, with studies of concurrent cytological preparations and microwave antigen retrieval.

    PubMed Central

    Binks, S; Clelland, C A; Ronan, J; Bell, J

    1997-01-01

    AIM: To document the frequency and extent of p53 gene product expression in paraffin sections of resected non-small cell carcinoma of the lung and in cytological preparations of the same tumours; to determine the effect of microwave antigen retrieval on antigen detection. METHODS: Representative paraffin sections of 50 non-small cell carcinomas were stained with an antibody to p53 gene product (DO-7) both with and without prior microwave antigen retrieval. Cytoblocks and cell smears obtained from 19 cases were similarly stained. RESULTS: Using a histochemical scoring system (0-300) which takes into account staining intensity and extent, 78% (n = 39) of microwave pretreated paraffin sections and 52% (n = 26) of non-pretreated sections scored between 5 and 300; p = 0.001; 56% (n = 28) of microwave pretreated sections and only 2% (n = 1) of non-pretreated sections scored between 100 and 300 (p = 0.0001); 75% of direct smears of tumours and 80% of cytoblocks stained similarly to the paraffin sections of the resected specimens. No smears or cytoblocks stained positively when the sections of the resected specimen were negative. CONCLUSIONS: As up to 78% of non-small cell lung carcinomas overexpress p53 gene product, this may prove to be a valuable diagnostic method in biopsy or cytological material when the morphological diagnosis is uncertain. Microwave antigen retrieval is effective on formalin fixed tissue. Images PMID:9215149

  4. EF5 in Measuring Tumor Hypoxia in Patients With Stage I-III Non-Small Cell Lung Cancer

    ClinicalTrials.gov

    2015-04-10

    Stage IA Non-Small Cell Lung Carcinoma; Stage IB Non-Small Cell Lung Carcinoma; Stage IIA Non-Small Cell Lung Carcinoma; Stage IIB Non-Small Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer

  5. Silver nanoparticles of Albizia adianthifolia: the induction of apoptosis in human lung carcinoma cell line

    PubMed Central

    2013-01-01

    Background Silver nanoparticles (AgNP), the most popular nano-compounds, possess unique properties. Albizia adianthifolia (AA) is a plant of the Fabaceae family that is rich in saponins. The biological properties of a novel AgNP, synthesized from an aqueous leaf extract of AA (AAAgNP), were investigated on A549 lung cells. Cell viability was determined by the MTT assay. Cellular oxidative status (lipid peroxidation and glutathione (GSH) levels), ATP concentration, caspase-3/-7, -8 and −9 activities were determined. Apoptosis, mitochondrial (mt) membrane depolarization (flow cytometry) and DNA fragmentation (comet assay) were assessed. The expression of CD95 receptors, p53, bax, PARP-1 and smac/DIABLO was evaluated by flow cytometry and/or western blotting. Results Silver nanoparticles of AA caused a dose-dependent decrease in cell viability with a significant increase in lipid peroxidation (5-fold vs. control; p = 0.0098) and decreased intracellular GSH (p = 0.1184). A significant 2.5-fold decrease in cellular ATP was observed upon AAAgNP exposure (p = 0.0040) with a highly significant elevation in mt depolarization (3.3-fold vs. control; p < 0.0001). Apoptosis was also significantly higher (1.5-fold) in AAAgNP treated cells (p < 0.0001) with a significant decline in expression of CD95 receptors (p = 0.0416). Silver nanoparticles of AA caused a significant 2.5-fold reduction in caspase-8 activity (p = 0.0024) with contrasting increases in caspase-3/-7 (1.7-fold vs. control; p = 0.0180) and −9 activity (1.4-fold vs. control; p = 0.0117). Western blots showed increased expression of smac/DIABLO (4.1-fold) in treated cells (p = 0.0033). Furthermore, AAAgNP significantly increased the expression of p53, bax and PARP-1 (1.2-fold; p = 0.0498, 1.6-fold; p = 0.0083 and 1.1-fold; p = 0.0359 respectively). Conclusion Data suggests that AAAgNP induces cell death in the A549 lung cells via the mt mediated intrinsic

  6. Antrodia cinnamomea alleviates cisplatin-induced hepatotoxicity and enhances chemo-sensitivity of line-1 lung carcinoma xenografted in BALB/cByJ mice.

    PubMed

    Huang, Tse-Hung; Chiu, Yi-Han; Chan, Yi-Lin; Wang, Hang; Li, Tsung-Lin; Liu, Chien-Yin; Yang, Cheng-Ta; Lee, Tzung-Yan; You, Jyh-Sheng; Hsu, Kuang-Hung; Wu, Chang-Jer

    2015-09-22

    Whereas cisplatin (cis-diamminedichloroplatinum II) is a first-line medicine to treat solid cancerous tumors, it often causes serious side effects. New medicines that have an equivalent or even better therapeutic effect but with free or less side effects than cisplatin are highly anticipated in cancer therapy. Recent reports revealed that Antrodia cinnamomea (AC) possesses hepatoprotective activity in addition to anticancer. In this study, we wanted to know whether AC enhances chemo-sensitivity of cisplatin and/or alleviates cisplatin-induced hepatotoxicity, as well as the underlying mechanisms thereof. Our results indicated that AC inhibited proliferation of line-1 lung carcinoma cells and rescued hepatic HepG2 cells from cisplatin-induced cell death in vitro. The fact is that AC and cisplatin synergized to constrain growth of line-1 lung carcinoma cells in BALB/cByJ mice. Quantitative real-time PCR further revealed that AC promoted expression of apoptosis-related genes, while it decreased expression of NF-κB and VEGF in tumor tissues. In liver, AC reduced cisplatin-induced liver dysfunctions, liver inflammation and hepatic apoptosis in addition to body weight restoration. In summary, AC is able to increase cisplatin efficacy by triggering expression of apoptosis-related genes in line-1 lung cancer cells as well as to protect liver from tissue damage by avoiding cisplatin-induced hepatic inflammation and cell death. PMID:26325335

  7. Antrodia cinnamomea alleviates cisplatin-induced hepatotoxicity and enhances chemo-sensitivity of line-1 lung carcinoma xenografted in BALB/cByJ mice

    PubMed Central

    Huang, Tse-Hung; Chiu, Yi-Han; Chan, Yi-Lin; Wang, Hang; Li, Tsung-Lin; Liu, Chien-Yin; Yang, Cheng-Ta; Lee, Tzung-Yan; You, Jyh-Sheng; Hsu, Kuang-Hung; Wu, Chang-Jer

    2015-01-01

    Whereas cisplatin (cis-diamminedichloroplatinum II) is a first-line medicine to treat solid cancerous tumors, it often causes serious side effects. New medicines that have an equivalent or even better therapeutic effect but with free or less side effects than cisplatin are highly anticipated in cancer therapy. Recent reports revealed that Antrodia cinnamomea (AC) possesses hepatoprotective activity in addition to anticancer. In this study, we wanted to know whether AC enhances chemo-sensitivity of cisplatin and/or alleviates cisplatin-induced hepatotoxicity, as well as the underlying mechanisms thereof. Our results indicated that AC inhibited proliferation of line-1 lung carcinoma cells and rescued hepatic HepG2 cells from cisplatin-induced cell death in vitro. The fact is that AC and cisplatin synergized to constrain growth of line-1 lung carcinoma cells in BALB/cByJ mice. Quantitative real-time PCR further revealed that AC promoted expression of apoptosis-related genes, while it decreased expression of NF-κB and VEGF in tumor tissues. In liver, AC reduced cisplatin-induced liver dysfunctions, liver inflammation and hepatic apoptosis in addition to body weight restoration. In summary, AC is able to increase cisplatin efficacy by triggering expression of apoptosis-related genes in line-1 lung cancer cells as well as to protect liver from tissue damage by avoiding cisplatin-induced hepatic inflammation and cell death. PMID:26325335

  8. Costunolide induces G1/S phase arrest and activates mitochondrial-mediated apoptotic pathways in SK-MES 1 human lung squamous carcinoma cells

    PubMed Central

    HUA, PEIYAN; ZHANG, GUANGXIN; ZHANG, YIFAN; SUN, MEI; CUI, RANJI; LI, XIN; LI, BINGJIN; ZHANG, XINGYI

    2016-01-01

    Despite the availability of several therapeutic options, a safer and more effective modality strategy is required for the treatment of lung cancer. Costunolide, a sesquiterpene lactone which isolated from the Saussurea lappa, has potent anticancer properties. In the present study, the effects of costunolide on cell viability, the cell cycle and apoptosis in SK-MES-1 human lung squamous carcinoma cells were investigated. Costunolide induced morphological changes and inhibited growth of SK-MES-1 cells growth. Flow cytometric analysis data demonstrated that costunolide significantly induced apoptosis of SK-MES-1 cells and induced cell cycle arrest at G1/S phase in a dose-dependent manner. Through upregulation in the expression of p53 and Bax, and downregulation in the expression of Bcl-2 and activation of caspase-3, costunolide-induced apoptosis was confirmed by western blot analysis. In addition, the significant loss of mitochondrial membrane potential indicated that costunolide may induce apoptosis via the mitochondria-dependent pathway in SK-MES-1 cells. These results highlight the potential effects of costunolide as an anti-cancer agent in a human lung squamous carcinoma cell line. PMID:27073552

  9. Insulin-like growth factor-1 receptor protein expression and gene copy number alterations in non-small cell lung carcinomas.

    PubMed

    Tsuta, Koji; Mimae, Takahiro; Nitta, Hiroaki; Yoshida, Akihiko; Maeshima, Akiko M; Asamura, Hisao; Grogan, Thomas M; Furuta, Koh; Tsuda, Hitoshi

    2013-06-01

    Insulin-like growth factor-1 receptor (IGF-1R) is a tyrosine kinase receptor implicated in the pathogenesis of several malignancies and is potentially an attractive target for anticancer treatment. In this study, we included 379 patients who underwent surgical resection (179 diagnosed as having adenocarcinoma [ADC]; 150, squamous cell carcinoma [SCC]; 41, sarcomatoid carcinoma and 9, large cell carcinoma). IGF-1R expression and gene copy number were assessed by immunohistochemistry and bright-field in situ hybridization (BISH), respectively. IGF-1R expression in non-small cell lung carcinoma was observed in 41.4% of samples and was more prevalent in SCC (69.3%) than in ADC (25.1%), large cell carcinoma (33.3%), and sarcomatoid carcinoma (12.2%) (P < .001). Among ADCs, most mucinous ADCs (75%) showed strong membranous staining with the IGF-1R antibody. Compared with protein expression, IGF-1R gene alteration was rare (8.4%). A statistically significant correlation between IGF-1R expression and positive IGF-1R BISH was observed (γ = 0.762, P < .001). IGF-1R-positive tumors were more common in smokers (P = .004), and these tumors were larger (P = .006) than the IGF-1R-negative tumors. IGF-1R BISH positivity was not correlated with any clinicopathologic factor. IGF-1R expression and IGF-1R BISH positivity were not correlated with overall survival. IGF-1R is highly expressed in SCC and mucinous ADC, although copy number alterations in the IGF-1R gene were rare. These findings may have important implications for future anti-IGF-1R therapeutic approaches. PMID:23266446

  10. Synthesis of peptide and pseudopeptide amides inhibiting the proliferation of small cell and epithelial types of lung carcinoma cells.

    PubMed

    Nyéki, O; Rill, A; Schon, I; Orosz, A; Schrett, J; Bartha, L; Nagy, J

    1998-12-01

    Small cell lung cancer (SCLC) cell lines produce and secrete various peptide hormones, e.g. bombesin (BN)/gastrin releasing peptide (GRP) like peptides that are proposed to function as their autocrine growth factors. To inhibit the proliferative effect of these hormones we have synthesized short chain BN[7-14]-analogues replacing the C-terminal peptide bond by a methylene-amino (-CH2NH-) unit and introducing D-Phe or D-Ser into position 12. As several substance P (SP) analogues were found to inhibit the growth of SCLC cells, some short chain SP-analogues have been synthesized. (Pseudo)octapeptides were synthesized in solution, by fragment condensation using the DCC/HOPfp method. Fragments and SP-analogues were synthesized stepwise using pentafluorophenyl esters. The resistance to hydrolysis of the reduced peptide bond made permitted exact quantification of the Leupsi(CH2NH)Leu pseudopeptide in hydrolysates. The binding ability of both types of peptides to BN-receptors on Swiss 3T3 mouse fibroblast cells and their antiproliferative effect on NCI-H69 human SCLC cell line have been tested and compared with a short chain SP-antagonist pHOPA-D-Trp-Phe-D-Trp-Leu-Leu-NH2 (R) previously described as a potent inhibitor of SCLC proliferation. While BN-analogues showed weak activity in inhibition of proliferation of SCLC cells, SP-analogues 6: D-MePhe-D-Trp-Phe-D-Trp-Leu(psi)(CH2NH)-Leu-NH2 and 7: D-MePhe-DTrp-Phe-D-Trp-Leu-MPA, in spite of greatly diminished affinity towards the BN-receptor, inhibited SCLC proliferation more effectively than R (6: IC50 = 2 microM, 7: IC50 = 5 microM and R: IC50 = 10 microM). Moreover, 6 inhibited the respiratory activity of SK-MES 1 epithelial type of lung carcinoma cells in proliferating but not in the quiescent state, suggesting that the antiproliferative effect of these compounds is not due to simple cytotoxicity. These short chain analogues of SP might be promising candidates as therapeutic agents in the treatment of SCLC. PMID:9927255

  11. The Impact of Coexisting Asthma, Chronic Obstructive Pulmonary Disease and Tuberculosis on Survival in Patients with Lung Squamous Cell Carcinoma

    PubMed Central

    Huang, Jing-Yang; Jian, Zhi-Hong; Ndi Nfor, Oswald; Jhang, Kai-Ming; Ku, Wen-Yuan; Ko, Pei-Chieh; Jan, Shiou-Rung; Ho, Chien-Chang; Lung, Chia-Chi; Pan, Hui-Hsien; Liang, Yu-Chiu; Liaw, Yung-Po

    2015-01-01

    Background Pulmonary diseases [asthma, chronic obstructive pulmonary disease (COPD), and tuberculosis (TB)] are associated with lung cancer mortality. However, the relationship between coexisting pulmonary diseases and survival in patients with lung squamous cell carcinoma (SqCC) has not been well defined. Methods Patients newly diagnosed with SqCC between 2003 and 2008 were identified by linking the National Health Insurance Research Database and Taiwan Cancer Registry Database. Cases with SqCC were followed up until death, loss to follow-up, or study end in 2010. Information on health status, date of death and the main causes of death was ascertained from the National Death Registry Database. Cox proportional hazard regression was used to calculate the hazard ratio (HR) of coexisting asthma, COPD and/or TB. Results During the study period, a total of 5406 cases with SqCC were enrolled. For all cause-mortality, HRs were 1.08 [95% confidence interval (CI), 0.99–1.18], 1.04 (95% CI, 0.97–1.12), and 1.14 (95% CI, 1.00–1.31) for individuals with asthma, COPD, and TB, respectively. Specifically, among men with coexisting pulmonary diseases, the HRs were 1.56 (95% CI, 1.23–1.97) and 1.11 (95% CI, 1.00–1.24) for individuals with asthma+COPD+TB and asthma+COPD, respectively. Among male patients with stage III SqCC, HRs were 3.41 (95%CI, 1.27–9.17) and 1.65 (95%CI, 1.10–2.47) for individuals with asthma+TB and asthma+COPD+TB, respectively. Among male patients with stage IV SqCC, HRs were 1.40 (95%CI, 1.00–1.97) and 1.25 (95%CI, 1.03–1.52) for individuals with asthma+ COPD+TB and asthma. Among female patients with stage I and II, HR was 0.19 (95%CI, 005–0.77) for individuals with asthma. Conclusions Coexisting pulmonary diseases increased the risk of mortality from SqCC in male patients. For female patients with early stage SqCC, pre-existing asthma decreased mortality. These patients deserve greater attention while undergoing cancer treatment. PMID

  12. Clinical and metabolic parameters in non-small cell lung carcinoma and colorectal cancer patients with and without KRAS mutations.

    PubMed

    Yilmaz, Ahmet; Mohamed, Nehad; Patterson, Kara A; Tang, Yan; Shilo, Konstantin; Villalona-Calero, Miguel A; Davis, Michael E; Zhou, Xiao-Ping; Frankel, Wendy; Otterson, Gregory A; Zhao, Weiqiang

    2014-09-01

    Lung cancer (LC) and colorectal cancer (CRC) are the first and second deadliest types of cancer worldwide. EGFR-based therapy has been used in the treatment of these cancers with variable success. Presence of mutations in the KRAS driver oncogene, possibly induced by environmental factors such as carcinogens in diet and cigarette smoke, may confer worse prognosis and resistance to treatment for reasons not fully understood. Data on possible associations between KRAS mutational status and clinical and metabolic parameters, which may help in clinical management, as well as in identifying risk factors for developing these cancers, are limited in the current literature. We sequenced the KRAS gene and investigated the associations of variations in 108 patients with non-small cell lung carcinoma (NSCLC), the most common form of LC, and in 116 patients with CRC. All of the mutations originated from the guanosine nucleotide and over half of all transversions in NSCLC and CRC were c.34 G>T and c.35 G>T, respectively. c.35 G>A was the most frequent type of transition in both cancers. Excluding smoking, the clinical and metabolic parameters in patients carrying mutant and wild type KRAS were similar except that the CRC patients with transversion mutations were 8.6 years younger than those carrying the transitions (P < 0.01). Dyslipidemia, hypertension, family cancer history, and age of diagnosis older than 60 years were more frequent in NSCLC than CRC (P ≤ 0.04). These results suggest that most of the clinical and metabolic parameters investigated in this study are probably not associated with the more aggressive phenotype and differences in response to EGFR-based treatment previously reported in patients with KRAS mutations. However, the increased rates of abnormal metabolic parameters in patients with NSCLC in comparison to CRC indicate that these parameters may be more important in the management of NSCLC. CRC patients carrying transition mutations are older than those

  13. Treatment with Huisheng oral solution inhibits the development of pulmonary thromboembolism and metastasis in mice with Lewis lung carcinoma.

    PubMed

    Wang, Wei; Wang, Hong; Wang, Chun-Mei; Gou, Si; Chen, Zhong-Hua; Guo, Jie

    2014-01-01

    The aim of this study was to investigate whether Huisheng oral solution (HSOS) has an inhibitory effect on the development of pulmonary thrombosis and metastasis in mice with Lewis lung carcinoma (LLC), and to explore the possible mechanisms involved. A mouse model of LLC was developed, and model mice were divided into either a treatment group or a control group to undergo treatment with HSOS or normal saline. Normal mice treated with saline were used as normal controls. On day 25 after treatment, blood samples were drawn from the eyes of half the mice in each group to determine blood cell counts and plasma levels of D-Dimer and vascular endothelial growth factor (VEGF), while heart blood samples were collected from the remaining mice to measure the rate of thrombin-induced platelet aggregation. For all mice, pathological analyses of the cerebrum, lung, mesentery, femoral vein, external iliac vein and spleen were performed. Tumors were weighed to assess the impact of HSOS treatment on tumor growth, and the number of thrombi, metastatic nodules and neovessels in the tumor tissue were counted. In addition, 24 normal New Zealand rabbits were divided into two groups and treated with either HSOS or normal saline to determine the rates of ADP-, collagen- or thrombin-induced platelet aggregation. Compared with the model group, HSOS treatment decreased the incidence of pulmonary thromboembolism and metastasis, the number of metastatic nodules, the plasma levels of D-dimer and VEGF, the rate of collagen-induced platelet aggregation in rabbits and the numbers of leukocytes and tumor neovessels (P<0.05 for all). It increased the thymus and spleen coefficients and the number of platelets (P<0.05 for all), but had no significant effect on thrombin-induced platelet aggregation in mice and rabbits, ADP-induced platelet aggregation in rabbits, or the number of red blood cells. The reduced rate of tumor growth was 9.7% in mice treated with HSOS. HSOS treatment effectively reduced

  14. Treatment with Huisheng oral solution inhibits the development of pulmonary thromboembolism and metastasis in mice with Lewis lung carcinoma

    PubMed Central

    WANG, WEI; WANG, HONG; WANG, CHUN-MEI; GOU, SI; CHEN, ZHONG-HUA; GUO, JIE

    2014-01-01

    The aim of this study was to investigate whether Huisheng oral solution (HSOS) has an inhibitory effect on the development of pulmonary thrombosis and metastasis in mice with Lewis lung carcinoma (LLC), and to explore the possible mechanisms involved. A mouse model of LLC was developed, and model mice were divided into either a treatment group or a control group to undergo treatment with HSOS or normal saline. Normal mice treated with saline were used as normal controls. On day 25 after treatment, blood samples were drawn from the eyes of half the mice in each group to determine blood cell counts and plasma levels of D-Dimer and vascular endothelial growth factor (VEGF), while heart blood samples were collected from the remaining mice to measure the rate of thrombin-induced platelet aggregation. For all mice, pathological analyses of the cerebrum, lung, mesentery, femoral vein, external iliac vein and spleen were performed. Tumors were weighed to assess the impact of HSOS treatment on tumor growth, and the number of thrombi, metastatic nodules and neovessels in the tumor tissue were counted. In addition, 24 normal New Zealand rabbits were divided into two groups and treated with either HSOS or normal saline to determine the rates of ADP-, collagen- or thrombin-induced platelet aggregation. Compared with the model group, HSOS treatment decreased the incidence of pulmonary thromboembolism and metastasis, the number of metastatic nodules, the plasma levels of D-dimer and VEGF, the rate of collagen-induced platelet aggregation in rabbits and the numbers of leukocytes and tumor neovessels (P<0.05 for all). It increased the thymus and spleen coefficients and the number of platelets (P<0.05 for all), but had no significant effect on thrombin-induced platelet aggregation in mice and rabbits, ADP-induced platelet aggregation in rabbits, or the number of red blood cells. The reduced rate of tumor growth was 9.7% in mice treated with HSOS. HSOS treatment effectively reduced

  15. [RAdio-chemo-surgical combined treatment of non-small cell lung carcinoma N2].

    PubMed

    Rovea, P; Sola, B; Boidi Trotti, A; Gabriele, A M; Fracchia, F; Casadio, C; Bretti, S

    1993-06-01

    As yet, no optimal treatment for stage-IIIA non-small-cell lung cancer (NSCLC) has been established. Particularly, in the patients with stage-IIIA N2 disease, surgical resection for cure is limited to few selected patients. Of late, a number of studies have suggested that such treatment modalities as chemotherapy, radiotherapy and surgery might be combined to improve treatment efficacy. Based on these conclusions, a cooperative study for N2 NSCLC patients was performed. Treatment included continuous CDDP infusion (6 mg/m2/day) and concomitant irradiation. Fifteen patients were examined. After neoadjuvant treatment, 4 patients were found to have unresectable lesions for local disease progression or metastasis. Eleven patients underwent complete resection (73% resectability). Follow-up ranged 6 to 32 months: 6 patients are now free from relapse (respectively at 31, 28, 23, 14, 12 and 3 months) and 1 is alive with adrenal gland metastasis. Overall and disease-free survival rates are 40.6% and 31.5%, respectively. Our preliminary results indicated that this protocol is well tolerated. Resectability was good and tumor sterilization rate was satisfying (complete T and N sterilization in 6 cases, sterilization of either T or N in 3 cases). The patients with non-adenocarcinoma histology exhibited better local control and prognosis than those with histologic diagnosis of adenocarcinoma. PMID:8393206

  16. Curcumin lowers erlotinib resistance in non-small cell lung carcinoma cells with mutated EGF receptor.

    PubMed

    Li, Shanqun; Liu, Zilong; Zhu, Fen; Fan, Xiaohong; Wu, Xiaodan; Zhao, Heng; Jiang, Liyan

    2013-01-01

    Non-small cell lung cancer (NSCLC) patients with activating mutations in the epidermal growth factor receptor (EGFR) are responsive to erlotinib, an EGFR-tyrosine kinase inhibitor (EGFR-TKI). However, patients with secondary somatic EGFR mutations are resistant to EGFR-TKI treatment. In this study, we investigated the effect of curcumin on the tumor growth of erlotinib-resistant NSCLC cells. Cell proliferation was determined by MTT assay. Apoptosis was examined using TUNEL staining. Protein expression of genes was determined by Western blot. Tumor growth was assessed in a xenograft mouse model. Results showed that erlotinib had a stronger effect on the induction of apoptosis in erlotinib-sensitive PC-9 cells but showed a weaker effect on erlotinib-resistant H1975 and H1650 cells than cisplatin and curcumin. Furthermore, curcumin significantly increased the cytotoxicity of erlotinib to erlotinib-resistant NSCLC cells, enhanced erlotinib-induced apoptosis, downregulated the expressions of EGFR, p-EGFR, and survivin, and inhibited the NF-κB activation in erlotinib-resistant NSCLC cells. The combination of curcumin and erlotinib exhibited the same effects on apoptosis as the combination of curcumin and cisplatin in erlotinib-resistant NSCLC cells. Moreover, the combined treatment of curcumin and erlotinib significantly inhibited tumor growth of erlotinib-resistant NSCLC cells in vivo. Our results indicate that curcumin is a potential adjuvant for NSCLC patients during erlotinib treatment. PMID:24512728

  17. Genetic variation in SIRT1 affects susceptibility of lung squamous cell carcinomas in former uranium miners from the Colorado plateau

    PubMed Central

    Leng, Shuguang; Picchi, Maria A.; Liu, Yushi; Thomas, Cynthia L.; Willis, Derall G.; Bernauer, Amanda M.; Carr, Teara G.; Mabel, Padilla T.; Han, Younghun; Amos, Christopher I.; Lin, Yong; Stidley, Christine A.; Gilliland, Frank D.; Jacobson, Marty R.; Belinsky, Steven A.

    2013-01-01

    Epidemiological studies of underground miners suggested that occupational exposure to radon causes lung cancer with squamous cell carcinoma (SCC) as the predominant histological type. However, the genetic determinants for susceptibility of radon-induced SCC in miners are unclear. Double-strand breaks induced by radioactive radon daughters are repaired primarily by non-homologous end joining (NHEJ) that is accompanied by the dynamic changes in surrounding chromatin, including nucleosome repositioning and histone modifications. Thus, a molecular epidemiological study was conducted to assess whether genetic variation in 16 genes involved in NHEJ and related histone modification affected susceptibility for SCC in radon-exposed former miners (267 SCC cases and 383 controls) from the Colorado plateau. A global association between genetic variation in the haplotype block where SIRT1 resides and the risk for SCC in miners (P = 0.003) was identified. Haplotype alleles tagged by the A allele of SIRT1 rs7097008 were associated with increased risk for SCC (odds ratio = 1.69, P = 8.2×10−5) and greater survival in SCC cases (hazard ratio = 0.79, P = 0.03) in miners. Functional validation of rs7097008 demonstrated that the A allele was associated with reduced gene expression in bronchial epithelial cells and compromised DNA repair capacity in peripheral lymphocytes. Together, these findings substantiate genetic variation in SIRT1 as a risk modifier for developing SCC in miners and suggest that SIRT1 may also play a tumor suppressor role in radon-induced cancer in miners. PMID:23354305

  18. Profiling Analysis of Histone Modifications and Gene Expression in Lewis Lung Carcinoma Murine Cells Resistant to Anti-VEGF Treatment

    PubMed Central

    Du, Yanhua; Chen, Kaiming; Liu, Zhenping; Li, Bing; Li, Jie; Tao, Fei; Gu, Hua; Jiang, Cizhong; Fang, Jianmin

    2016-01-01

    Tumor cells become resistant after long-term use of anti-VEGF (vascular endothelial growth factor) agents. Our previous study shows that treatment with a VEGF inhibitor (VEGF-Trap) facilitates to develop tumor resistance through regulating angiogenesis-related genes. However, the underlying molecular mechanisms remain elusive. Histone modifications as a key epigenetic factor play a critical role in regulation of gene expression. Here, we explore the potential epigenetic gene regulatory functions of key histone modifications during tumor resistance in a mouse Lewis lung carcinoma (LLC) cell line. We generated high resolution genome-wide maps of key histone modifications in sensitive tumor sample (LLC-NR) and resistant tumor sample (LLC-R) after VEGF-Trap treatment. Profiling analysis of histone modifications shows that histone modification levels are effectively predictive for gene expression. Composition of promoters classified by histone modification state is different between LLC-NR and LLC-R cell lines regardless of CpG content. Histone modification state change between LLC-NR and LLC-R cell lines shows different patterns in CpG-rich and CpG-poor promoters. As a consequence, genes with different level of CpG content whose gene expression level are altered are enriched in distinct functions. Notably, histone modification state change in promoters of angiogenesis-related genes consists with their expression alteration. Taken together, our findings suggest that treatment with anti-VEGF therapy results in extensive histone modification state change in promoters with multiple functions, particularly, biological processes related to angiogenesis, likely contributing to tumor resistance development. PMID:27362259

  19. [Anti-tumor effect of the whole worm extract of Ascaris lumbricoides on Lewis lung carcinoma in mice].

    PubMed

    Yang, Xiao-Jun; Yang, Jun-Ping; Huang, Yan-Qin; Liang, Hua; Yuan, Keng

    2013-12-01

    Forty-five C57BL/6 mice were randomly divided into five groups (A-E). Group B and D served as the control group of A and C. Each mouse of group A was intraperitoneally injected with 0.1 ml whole worm extract of Ascaris lumbricoides every other day, and 10 days later injected with 0.1 ml Lewis lung carcinoma (LLC) cells at right axillary subcutaneously region. Mice of group B were injected with normal saline and then developed tumor model. Each mouse of group C was injected with 0.1 ml LLC cells, and two days later, injected with 0.1 ml whole worm extract of A. lumbricoides every other day for 5 times. After the tumor model developed, mice in group D were injected with normal saline. Group E was the negative control group. Time intervals between implantation and active growth and tumor weight were recorded. Tumor inhibition rate was calculated. The average time interval between tumor implantation and measurable tumor growth for groups A, B, C and D was (7.0 +/-1.1), (6.0 +/- 0.7), (9.0 +/- 1.2) and (7.0 +/- 0.9) days. Tumor weight of [(338.9 +/- 282.2) mg] (P < 0.05). The tumor inhibition rate group A [(722.2 +/- 413.5) mg] was heavier than that of group B was the highest in group C (33.3%). Tumor weight of group C [(237.8 +/- 101.8) mg] was lighter than that of group D [(356.7 +/- 176.9) mg] (P < 0.05). The results indicated that the tumor formation is affected by the whole worm extract of A. lumbricoides which may have an inhibitory effect on tumour growth. PMID:24818416

  20. Chemical constituents of Rhododendron formosanum show pronounced growth inhibitory effect on non-small-cell lung carcinoma cells.

    PubMed

    Way, Tzong-Der; Tsai, Shang-Jie; Wang, Chao-Min; Ho, Chi-Tang; Chou, Chang-Hung

    2014-01-29

    The aim of the present study was to investigate whether Rhododendron formosanum Hemsl. (Ericaceae), an endemic species in Taiwan, exhibits antineoplastic potential against non-small-cell lung carcinoma (NSCLC). R. formosanum was successively extracted with methanol and then separated into dichloromethane (RFL-DCM), ethyl acetate (RFL-EA), n-butanol (RFL-BuOH), and water (RFL-H2O) fractions. Among these extracts, RFL-EA exhibited the most effective antineoplastic effect. This study also demonstrated that fractions 2 and 3 from the RFL-EA extract (RFL-EA-2, RFL-EA-3) possessed the strongest antineoplastic potential against NSCLC cells. The major phytochemical constituents of RFL-EA-2 and RFL-EA-3 were ursolic acid, oleanolic acid, and betulinic acid. This study indicated that ursolic acid demonstrated the most efficient antineoplastic effects on NSCLC cells. Ursolic acid inhibited growth of NSCLC cells in a dose- and time-dependent manner and stimulated apoptosis. Apoptosis was substantiated by activation of caspase-3 and -9, and a decrease in Bcl-2 and an elevation of the Bax were also observed following ursolic acid treatment. Ursolic acid activated AMP-activated protein kinase (AMPK) and then inhibited the mammalian target of rapamycin (mTOR), which controls protein synthesis and cell growth. Moreover, ursolic acid decreased the expression and/or activity of lipogenic enzymes, such as acetyl-CoA carboxylase (ACC) and fatty acid synthase (FASN) via AMPK activation. Collectively, these data provide insight into the chemical constituents and anticancer activity of R. formosanum against NSCLC cells, which are worthy of continued study. PMID:24447325

  1. Glucose-induced thermogenesis in patients with small cell lung carcinoma. Before and after inhibition of tumour growth by chemotherapy.

    PubMed

    Simonsen, L; Bülow, J; Sengeløv, H; Madsen, J; Ovesen, L

    1993-07-01

    Seven weight-losing patients with histologically verified small cell lung carcinoma were given an oral glucose load of 75 g before and at least 3 weeks after the end of chemotherapy to examine the effect of glucose on whole body and skeletal muscle thermogenesis before and after reduction of tumour. Whole body energy expenditure was measured by the open circuit ventilated hood system. Forearm blood flow was measured by venous-occlusion strain-gauge plethysmography. The uptake of oxygen in skeletal muscle was calculated as the product of the forearm blood flow and the difference in a-v oxygen concentration. Whole body resting energy expenditure (REE) did not increase, it was 4.4 +/- 0.3 kJ min-1 (mean +/- SE) before chemotherapy and 4.4 +/- 0.2 kJ min-1 after chemotherapy. The glucose-induced thermogenesis in the 180 min following the glucose load was 93.6 +/- 9.9 kJ 180 min-1 before chemotherapy. This is significantly increased compared to that found in a healthy control group (74.7 +/- 4.8 kJ 180 min-1, P < 0.02). The glucose-induced thermogenesis was significantly reduced to 47.7 +/- 10.2 kJ 180 min-1 (P < 0.05) after chemotherapy. The oxygen uptake in resting skeletal muscles was 6.9 +/- 0.3 mumol 100 g-1 min-1 before chemotherapy and 7.0 +/- 0.7 mumol 100 g-1 min-1 after chemotherapy. This did not increase during the first 90 min following the glucose load in either investigations. In the period 90-180 min following the glucose load, the oxygen uptake was significantly increased before chemotherapy as compared to after chemotherapy, which suggests that the reduced whole body thermogenesis after chemotherapy in part was due to reduced skeletal muscle thermogenesis. PMID:8396523

  2. High-Dose Conformal Radiotherapy for Patients With Stage III Non-Small-Cell Lung Carcinoma

    SciTech Connect

    Nakayama, Hidetsugu; Satoh, Hiroaki; Kurishima, Koichi; Ishikawa, Hiroichi; Tokuuye, Koichi

    2010-11-01

    Purpose: To determine the effectiveness of high-dose conformal radiotherapy to the involved field for patients with Stage III non-small-cell lung cancer (NSCLC). Methods and Materials: Between May 1999 and April 2006, a total of 100 consecutive patients with inoperable Stage IIIA or IIIB NSCLC with a performance score of 0 to 2 and treatment by radical radiotherapy combined with chemotherapy were included. Up to August 2002, 33 patients underwent conventional radiotherapy of 56 Gy to 66 Gy using anteroposterior opposite ports to the primary tumor and elective lymph nodes (conventional group). After September 2002, the remaining 67 patients underwent high-dose radiotherapy of 66 Gy to 84 Gy to the involved volume with three-dimensional (3-D) conformal radiotherapy (conformal group). Results: The median survival was 13.2 months (95% confidence interval [CI], 7.5-18.5 months) in the conventional group and 17.3 months (95% CI, 10.7- 24.0 months) in the conformal group. The overall survival at 3 years were 9.1% (95% CI, -0.7-18.9%) in the conventional group and 31.0% (95% CI, 18.9-43.1%) in the conformal group; the conformal group had a significantly better overall survival (p < 0.05). The radiotherapy method (hazard ratio = 0.55, p < 0.05) and performance status (hazard ratio = 1.48, p < 0.05) were shown to be statistically significant independent prognostic factors. Conclusions: Based on the practical experience reported here, 3-D conformal radiotherapy allowed dose escalation without excessive toxicity, and may improve overall survival rates for patients with Stage III NSCLC.

  3. Targeting SHP2 for EGFR inhibitor resistant non-small cell lung carcinoma

    SciTech Connect

    Xu, Jie; Zeng, Li-Fan; Shen, Weihua; Turchi, John J.; Zhang, Zhong-Yin

    2013-10-04

    Highlights: •SHP2 is required for EGFR inhibitor resistant NSCLC H1975 cell proliferation. •SHP2 inhibitor blocks EGF-stimulated ERK1/2 activation and proliferation. •SHP2 inhibitor exhibits marked anti-tumor activity in H1975 xenograft mice. •SHP2 inhibitor synergizes with PI3K inhibitor in suppressing cell growth. •Targeting SHP2 represents a novel strategy for EGFR inhibitor resistant NSCLCs. -- Abstract: Targeted therapy with inhibitors of epidermal growth factor receptor (EGFR) has produced a noticeable benefit to non-small cell lung cancer (NSCLC) patients whose tumors carry activating mutations (e.g. L858R) in EGFR. Unfortunately, these patients develop drug resistance after treatment, due to acquired secondary gatekeeper mutations in EGFR (e.g. T790M). Given the critical role of SHP2 in growth factor receptor signaling, we sought to determine whether targeting SHP2 could have therapeutic value for EGFR inhibitor resistant NSCLC. We show that SHP2 is required for EGF-stimulated ERK1/2 phosphorylation and proliferation in EGFR inhibitor resistant NSCLC cell line H1975, which harbors the EGFR T790M/L858R double-mutant. We demonstrate that treatment of H1975 cells with II-B08, a specific SHP2 inhibitor, phenocopies the observed growth inhibition and reduced ERK1/2 activation seen in cells treated with SHP2 siRNA. Importantly, we also find that II-B08 exhibits marked anti-tumor activity in H1975 xenograft mice. Finally, we observe that combined inhibition of SHP2 and PI3K impairs both the ERK1/2 and PI3K/AKT signaling axes and produces significantly greater effects on repressing H1975 cell growth than inhibition of either protein individually. Collectively, these results suggest that targeting SHP2 may represent an effective strategy for treatment of EGFR inhibitor resistant NSCLCs.

  4. Effects of Cx43 gene modification on the proliferation and migration of the human lung squamous carcinoma cell line NCI-H226.

    PubMed

    Zang, J-P; Wei, R

    2015-01-01

    In this study, the human lung squamous carcinoma cell line NCI-H226 was transfected with the recombinant plasmid pBudCE4.1_Cx43 to explore the role of the Cx43 gene in cell growth, cell cycle, and tumor migration. pBudCE4.1-Cx43 was transfected into human lung squamous carcinoma NCI-H226 cells using Lipofectamine TM2000. The mRNA and protein expressions of Cx43 in the transfected cells were detected by reverse transcriptase polymerase chain reaction and western blot analysis. The cell-cell communication was detected using the scratch dye tracer method and the cell cycle was detected by flow cytometry. The CCK-8 proliferation, scratch healing, and cell invasion assays were performed to evaluate the effect of the Cx43 gene transfection on the proliferation, migration, and invasive abilities of NCI-H226 cells. Cx43 mRNA and protein expressions and the fluorescence intensity in the scratch healing test were significantly higher in the experimental group than those in the control and blank groups (P < 0.05 and < 0.01, respectively). The CCK-8 proliferation assay and the scratch healing experiment revealed significantly inhibited NCI-H226 cell proliferation (especially 72 h after incubation) and cell migration, respectively, in the experimental group, compared to the control and blank groups (P < 0.001 and <0.05, respectively). The transwell chamber test showed a statistically significant decrease in the invasive ability of NCI-H226 cells in the experimental group (P < 0.05). Therefore, Cx43 gene transfection could inhibit the migration of human lung squamous carcinoma cell line NCI-H226, thereby inhibiting tumor cell proliferation. PMID:26535624

  5. [Accuracy of multislice CT in restaging patients with non-small cell lung carcinoma after neoadjuvant chemotherapy using a multiparametric approach].

    PubMed

    Mazzei, Maria Antonietta; Guerrini, Susanna; Genovese, Eugenio Annibale; Voltolini, Luca; Mazzei, Francesco G; Volterrani, Luca; Macarini, Luca

    2012-11-01

    The aim of this study was to assess diagnostic accuracy of multislice CT in restaging patients with N2 non-small cell lung carcinoma after neoadjuvant chemotherapy, using a multiparametric approach as compared with traditional size-based radiological criteria. All patients staged as N2 at histologic examination after neoadjuvant chemotherapy were correctly staged with multislice CT (sensitivity, specificity, positive and negative predictive value, and accuracy were 100%, 80%, 85%, 100% and 93,7% respectively, vs 34%, 60%, 34%, 60% and 50% using size-based criteria), suggesting that a multiparametric approach results in improved diagnostic accuracy. PMID:23096733

  6. Stereotactic Body Radiation Therapy in Treating Patients With Metastatic Breast Cancer, Non-small Cell Lung Cancer, or Prostate Cancer

    ClinicalTrials.gov

    2016-06-17

    Male Breast Carcinoma; Prostate Adenocarcinoma; Recurrent Breast Carcinoma; Recurrent Non-Small Cell Lung Carcinoma; Recurrent Prostate Carcinoma; Stage IV Breast Cancer; Stage IV Non-Small Cell Lung Cancer; Stage IV Prostate Cancer

  7. TUBERCULOSIS AND LUNG CANCER.

    PubMed

    Tamura, Atsuhisa

    2016-01-01

    The occurrence of pulmonary tuberculosis (PTB) and lung cancer as comorbidities has been extensively discussed in many studies. In the past, it was well known that lung cancer is a specific epidemiological successor of PTB and that lung cancer often develops in scars caused by PTB. In recent years, the relevance of the two diseases has drawn attention in terms of the close epidemiological connection and chronic inflammation-associated carcinogenesis. In Japanese case series studies, most lung cancer patients with tuberculous sequelae received supportive care alone in the past, but more recently, the use of aggressive lung cancer treatment is increasing. Many studies on PTB and lung cancer as comorbidities have revealed that active PTB is noted in 2-5% of lung cancer cases, whereas lung cancer is noted in 1-2% of active PTB cases. In such instances of comorbidity, many active PTB cases showed Type II (non-extensively cavitary disease) and Spread 2-3 (intermediate-extensive diseases) on chest X-rays, but standard anti-tuberculosis treatment easily eradicates negative conversion of sputum culture for M. tuberculosis; lung cancer cases were often stage III- IV and squamous cell carcinoma predominant, and the administration of aggressive treatment for lung cancer is increasing. The major clinical problems associated with PTB and lung cancer as comorbidities include delay in diagnosis (doctor's delay) and therapeutic limitations. The former involves two factors of radiographic interpretation: the principles of parsimony (Occam's razor) and visual search; the latter involves three factors of lung cancer treatment: infectivity of M.tuberculosis, anatomical limitation due to lung damage by tuberculosis, and drug-drug interactions between rifampicin and anti-cancer drugs, especially molecularly targeted drugs. The comorbidity of these two diseases is an important health-related issue in Japan. In the treatment of PTB, the possibility of concurrent lung cancer should be kept

  8. Alpha-carotene inhibits metastasis in Lewis lung carcinoma in vitro, and suppresses lung metastasis and tumor growth in combination with taxol in tumor xenografted C57BL/6 mice.

    PubMed

    Liu, Yi-Zhen; Yang, Chih-Min; Chen, Jen-Yin; Liao, Junn-Wang; Hu, Miao-Lin

    2015-06-01

    This study aimed to investigate the anti-metastatic activity of α-carotene (AC) in Lewis lung carcinoma (LLC) and in combination with taxol in LLC-xenografted C57BL/6 mice. Cell culture studies reveal that AC significantly inhibited invasion, migration and activities of matrix metalloproteinase (MMP)-2, -9 and urokinase plasminogen activator but increased protein expression of tissue inhibitor of MMP (TIMP)-1, -2 and plasminogen activator inhibitor (PAI)-1. These effects of AC are similar to those of β-carotene at the same concentration (2.5 μM). AC (2.5 μM) also significantly inhibited integrin β1-mediated phosphorylation of focal adhesion kinase (FAK) which then decreased the phosphorylation of MAPK family. Findings from the animal model reveal that AC treatment (5m g/kg) alone significantly decreased lung metastasis without affecting primary tumor growth, whereas taxol treatment (6 mg/kg) alone exhibited significant inhibition on both actions, as compared to tumor control group. AC treatment alone significantly decreased protein expression of integrin β1 but increased protein expression of TIMP-1 and PAI-1 without affecting protein expression of TIMP-2 and phosphorylation of FAK in lung tissues, whereas taxol treatment alone significantly increased protein expression of TIMP-1, PAI-1 and TIMP-2 but decreased protein expression of integrin β1 and phosphorylation of FAK. The combined treatment produced stronger actions on lung metastasis and lung tissues protein expression of TIMP-1, TIMP-2 and PAI-1. Overall, we demonstrate that AC effectively inhibits LLC metastasis and suppresses lung metastasis in combination with taxol in LLC-bearing mice, suggesting that AC could be used as an anti-metastatic agent or as an adjuvant for anti-cancer drugs. PMID:25736483

  9. LUMOR: an app for standardized control and monitoring of a porcine lung and its nutrient cycle.

    PubMed

    Lenz, Gregor; Frohner, Matthias; Sauermann, Stefan; Forjan, Mathias

    2014-01-01

    The outcome of the EU-funded project ElBik has been the lung simulator 'iLung', which imitates an actively breathing human lung with a porcine lung. In order to keep the explanted lung in a nearly physiological state during transportation from the slaughterhouse to the ventilation laboratory the tissue needs to be nourished and temperature controlled. The Project AlveoPic designs a mobile transport vehicle implementing an ISO/IEEE 11073-20601 compliant communication interface for the exchange of the physical parameters, alert messages and setpoint-values. An appropriate 11073 domain information model is designed and limitations of the defined services and attributes are identified. For monitoring purposes the Android App LUMOR is implemented providing a user with an easy-to-handle GUI. It was found, that alert capabilities and remote set features are not well supported in ISO/IEEE 11073-20601 at the moment and possible workarounds are discussed. PMID:24825688

  10. Phospholipid profiling identifies acyl chain elongation as a ubiquitous trait and potential target for the treatment of lung squamous cell carcinoma

    PubMed Central

    Marien, Eyra; Meister, Michael; Muley, Thomas; del Pulgar, Teresa Gomez; Derua, Rita; Spraggins, Jeffrey M.; Van de Plas, Raf; Vanderhoydonc, Frank; Machiels, Jelle; Binda, Maria Mercedes; Dehairs, Jonas; Willette-Brown, Jami; Hu, Yinling; Dienemann, Hendrik; Thomas, Michael; Schnabel, Philipp A.; Caprioli, Richard M.; Lacal, Juan Carlos; Waelkens, Etienne; Swinnen, Johannes V.

    2016-01-01

    Lung cancer is the leading cause of cancer death. Beyond first line treatment, few therapeutic options are available, particularly for squamous cell carcinoma (SCC). Here, we have explored the phospholipidomes of 30 human SCCs and found that they almost invariably (in 96.7% of cases) contain phospholipids with longer acyl chains compared to matched normal tissues. This trait was confirmed using in situ 2D-imaging MS on tissue sections and by phospholipidomics of tumor and normal lung tissue of the L-IkkαKA/KA mouse model of lung SCC. In both human and mouse, the increase in acyl chain length in cancer tissue was accompanied by significant changes in the expression of acyl chain elongases (ELOVLs). Functional screening of differentially expressed ELOVLs by selective gene knockdown in SCC cell lines followed by phospholipidomics revealed ELOVL6 as the main elongation enzyme responsible for acyl chain elongation in cancer cells. Interestingly, inhibition of ELOVL6 drastically reduced colony formation of multiple SCC cell lines in vitro and significantly attenuated their growth as xenografts in vivo in mouse models. These findings identify acyl chain elongation as one of the most common traits of lung SCC discovered so far and pinpoint ELOVL6 as a novel potential target for cancer intervention. PMID:26862848

  11. Imaging characteristic analysis of metastatic spine lesions from breast, prostate, lung, and renal cell carcinomas for surgical planning: Osteolytic versus osteoblastic

    PubMed Central

    Reddington, Justin A.; Mendez, Gustavo A.; Ching, Alex; Kubicky, Charlotte Dai; Klimo, Paul; Ragel, Brian T.

    2016-01-01

    Background: Surgeons treating metastatic spine disease can use computed tomography (CT) imaging to determine whether lesions are osteolytic, osteoblastic, or mixed. This enables treatment that considers the structural integrity of the vertebral body (VB), which is impaired with lytic lesions but not blastic lesions. The authors analyzed CT imaging characteristics of spine metastasis from breast, lung, prostate, and renal cell carcinomas (RCCs) to determine the metastasis patterns of each of these common tumors. Methods: The authors identified patients with metastatic spine disease treated during a 3-year period. Variables studied included age, sex, and cancer type. Lesions from breast, lung, prostate, and RCC primary lesions were selected for imaging analysis. Results: Sixty-six patients were identified: 17 had breast metastasis, 14 prostate, 18 lung, and 17 RCC. Breast cancer metastasis involved 33% of VBs with 56%, 20%, and 24% osteolytic, osteoblastic, and mixed, respectively. Prostate cancer metastasis involved 35% of VBs with 14%, 62%, and 24% osteolytic, osteoblastic, and mixed, respectively. Lung cancer metastasis involved 13% of VBs with 64%, 33%, and 3% osteolytic, osteoblastic, and mixed, respectively. RCC metastasis involved 11% of VBs with 91%, 7%, and 2% osteolytic, osteoblastic, and mixed lesions, respectively. Conclusions: To improve surgical planning, we advocate the use of CT prior to surgery to evaluate whether spine metastases are osteolytic or osteoblastic. In cases of osteolytic lesions, the concern is of segmental instability requiring reconstruction and the risk for screw pull out should instrumentation be considered. In cases of osteoblastic lesions, surgeons should consider debulking dense bone. PMID:27274410

  12. Alpha 1-acid glycoprotein concentration and molecular heterogeneity: relationship to oxprenolol binding in serum from healthy volunteers and patients with lung carcinoma or cirrhosis.

    PubMed Central

    Fraeyman, N F; Dello, C D; Belpaire, F M

    1988-01-01

    1. alpha 1-acid glycoprotein (AAG) concentration and molecular heterogeneity, and oxprenolol protein binding were studied in serum of 15 healthy volunteers, 14 patients with lung carcinoma and 17 patients with liver cirrhosis. 2. The AAG serum concentration was increased to 180.7% in patients with lung cancer and decreased to 73.4% in cirrhotic patients as compared with controls (P less than 0.05). 3. The concanavalin A (conA) dependent heterogeneity of serum AAG was very similar in controls and patients with lung cancer: a ratio of 9/9/2 was obtained for the conA nonreactive, the conA weakly reactive and the conA strongly reactive subfraction respectively; in cirrhotic patients, the ratio shifted to 11/7/1. 4. The heterogeneity in electric charge, demonstrated by isoelectric focusing, was similar in the three groups of subjects: 70-80% of the focussed bands were found in the main three bands. 5. The binding of oxprenolol to serum proteins was increased in lung tumour patients and decreased in liver cirrhotic patients as compared with controls (P less than 0.05). There was no change in binding affinity and oxprenolol binding was significantly correlated to total AAG serum concentration and to the concentration of each of the conA dependent subtypes, in controls as well as in both patients groups. Images Figure 1 PMID:3203044

  13. Mutations and expression of the NFE2L2/KEAP1/CUL3 pathway in Chinese patients with lung squamous cell carcinoma

    PubMed Central

    Zhang, Yongxing; Fan, Hong; Fang, Shuo; Wang, Lin; Chen, Li; Jin, Yulin; Jiang, Wei; Lin, Zongwu; Shi, Yu

    2016-01-01

    Background Recent studies have reported an abnormally high alteration rate in the nuclear factor erythroid 2-like 2 (NFE2L2)/kelch-like ECH-associated protein 1 (KEAP1)/cullin 3 (CUL3) pathway. But the status of this pathway in Chinese patients with lung squamous cell carcinoma (SqCC) has not been thoroughly studied, and there are many uncertainties regarding the expression of pathway intermediates. Methods cDNA sequencing and TaqMan qRT-PCR were carried out in paired cancer and adjacent normal samples obtained from 100 Chinese patients with lung SqCC. Immunohistochemical staining was performed in 50 other paraffin-embedded specimens. Results We detected 47 mutations in 36 patients (36%), and 143 single nucleotide polymorphism (SNP) in 59 patients (59%), of which 41 mutations and 31 SNPs resulted in amino acid (AA) and possibly functional changes. By combining qRT-PCR and immunohistochemistry staining, we confirmed that the expression of NFE2L2 and KEAP1 were highly increased, while the expression of CUL3 was not significantly changed in lung SqCC samples from Chinese patients. Conclusions Considering the frequent mutations and abnormal expression, the NFE2L2/KEAP1/CUL3 pathway may play an important role in the therapy of Chinese patients with lung SqCC. PMID:27499952

  14. Dengue viruses can infect human primary lung epithelia as well as lung carcinoma cells, and can also induce the secretion of IL-6 and RANTES.

    PubMed

    Lee, Ying-Ray; Su, Ching-Yao; Chow, Nan-Haw; Lai, Wu-Wei; Lei, Huan-Yao; Chang, Chia-Lun; Chang, Tsuey-Yu; Chen, Shun-Hua; Lin, Yee-Shin; Yeh, Trai-Ming; Liu, Hsiao-Sheng

    2007-06-01

    Dengue viruses (DENV) are herein demonstrated for the first time as being able to infect and replicate in human primary lung epithelium and various lung cancer cell lines. The detection of dengue virus particles and viral negative strand RNA synthesis in the cell, in conjunction with the release of viral progenies in culture supernatants, support the notion that lung cells are susceptible to dengue virus infection. The replication efficiency of DENV in lung cancer cells from high to low is: DEN-2 (dengue virus type-2), DEN-3, DEN-4 and DEN-1. Moreover, the susceptibility of the six lung cancer cell lines to DEN-2 infection is: SW1573>A549>H1435; H23; H520; Bes2B. DEN-2 infection significantly increased the expression levels of IL-6 and RANTES in four of the six lung cancer cell lines, which is consistent with the high expression levels of these molecules in DHF/DSS patients. IL-6 expression induced by DEN-2 infection was NF-kappaB dependent. In summary, our results indicate that lung epithelial cell is a possible target of dengue viruses and IL-6 and RANTES may play pivotal roles in lung related immuno-pathogenesis. PMID:17416433

  15. Inonotus obliquus-derived polysaccharide inhibits the migration and invasion of human non-small cell lung carcinoma cells via suppression of MMP-2 and MMP-9.

    PubMed

    Lee, Ki Rim; Lee, Jong Seok; Song, Jeong Eun; Ha, Suk Jin; Hong, Eock Kee

    2014-12-01

    Polysaccharides isolated from the fruiting body of Inonotus obliquus (PFIO) are known to possess various pharmacological properties including antitumor activity. However, the anti-metastatic effect and its underlying mechanistic signaling pathway involved these polysaccharides in human non-small cell lung carcinoma remain unknown. The present study therefore aimed to determine the anti-metastatic potential and signaling pathways of PFIO in the highly metastatic A549 cells. We found that PFIO suppressed the migration and invasive ability of A549 cells while decreasing the expression levels and activity of matrix metalloproteinase (MMP)-2 and MMP-9. Furthermore, PFIO decreased the phosphorylation levels of mitogen-activated protein kinases (MAPKs) and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) as well as the expression level of COX-2, and inhibited the nuclear translocation of nuclear factor κB (NF-κB) in A549 cells. These results suggested that PFIO could suppress the invasion and migration of human lung carcinoma by reducing the expression levels and activity of MMP-2 and MMP-9 via suppression of MAPKs, PI3K/AKT, and NF-κB signaling pathways. PMID:25270791

  16. Induction of COX-2 protein expression by vanadate in A549 human lung carcinoma cell line through EGF receptor and p38 MAPK-mediated pathway

    SciTech Connect

    Chien, P.-S.; Mak, O.-T.; Huang, H.-J. . E-mail: haojen@mail.ncku.edu.tw

    2006-01-13

    Vanadate is a transition metal widely distributed in the environment. It has been reported that vanadate associated with air pollution particles can modify DNA synthesis, causing cell growth arrest, and apoptosis. Moreover, vanadium exposure was also found to cause the synthesis of inflammatory cytokines, such as interleukin-1, tumor necrosis factor-{alpha}, and prostaglandin E{sub 2}. Here, we found that exposure of A549 human lung carcinoma cells to vanadate led to extracellular signal-regulated kinase, c-Jun NH{sub 2}-terminal protein kinases (JNKs), p38 mitogen-activated protein kinase (p38) activation, and COX-2 protein expression in a dose-dependent manner. SB203580, a p38 MAPK inhibitor, but not PD098059 and SP600125, specific inhibitor of MKK1 and selective inhibitor of JNK, respectively, suppressed COX-2 expression. Furthermore, the epithelial growth factor (EGF) receptor specific inhibitor (PD153035) reduced vanadate-induced COX-2 expression. However, scavenging of vanadate-induced reactive oxygen species by catalase, a specific H{sub 2}O{sub 2} inhibitor, or DPI, an NADPH oxidase inhibitor, resulted in no inhibition on COX-2 expression. Together, we suggested that EGF receptor and p38 MAPK signaling pathway may be involved in vanadate-induced COX-2 protein expression in A549 human lung carcinoma cell line.

  17. Apoptotic potential of C-phycoerythrin from Phormidium sp. A27DM and Halomicronema sp. A32DM on human lung carcinoma cells.

    PubMed

    Madamwar, Datta; Patel, Dipak K; Desai, Swati N; Upadhyay, Kapil K; Devkar, Ranjitsinh V

    2015-01-01

    Phycobilisomes present in cyanobacteria are photosynthetic macromolecular protein complexes that are categorized into three types - phycoerythrins (high energy), phycocyanin (intermediate energy) and allophycocyanin (low energy). Structurally, they consist of α and β protein subunits and open chain tetrapyrrole prosthetic group (bilin chromophore), known for its antioxidant properties and therapeutic potential against a variety of physiological ailments. Phycoerythrins (C-PE) were purified from cyanobacterial strains Phormidium sp. A27DM and Halomicronema sp. A32DM and their respective apoptotic potentials were assessed on A549 human lung carcinoma cells. Both strains of cyanobacteria were cultured and the C-PE from each strain was extracted, quantified and characterized. C-PE accounted for a dose dependent decrement in cell viability, mitochondrial membrane potential and an increment in lactate dehydrogenase release. Higher doses of C-PE (of both strains) accounted for loss of cell viability and nuclear pycnosis. These findings were further substantiated with flow cytometry that revealed a cell arrest at G0/G1 phase and a high percentage of cells undergoing apoptosis following C-PE treatment. These results confirm the efficacy of C-PE from Phormidium sp. or Halomicronema sp. in triggering apoptotic cell death. This study is the first to report on apoptotic property of C-PE against A549 human lung carcinoma cells and warrants further studies to establish its anti-cancer potential. PMID:26535041

  18. Transthoracic fine-needle aspiration cytology of non-invasive, low-grade urothelial carcinoma with lung metastasis: A case report with review of the literature

    PubMed Central

    Vural, ÇiĞdem; Yildiz, Kürsat; Çabuk, Devrim; Akgül, Asli

    2015-01-01

    Radiological analyses in a 61-year-old patient being followed since 2005 for low-grade, non-invasive urothelial carcinoma (UC) (Ta) revealed a 5-cm pleural-based mass in the lower lobe of the right lung for which a subsequent transthoracic fine-needle aspiration cytology was performed. Upon observing the carcinoma cells consistent with UC metastasis, systemic chemotherapy was commenced. The patient underwent a metastatectomy based on the thoracic computerized tomography scan performed on the 4th month of treatment, which revealed notable regression. The resected tumor was morphologically similar to cells seen in the transthoracic fine-needle aspiration and was immunohistochemically positive for p63, uroplakin, thrombomodulin, CK7 and CK20 at varying degrees but was negative for TTF-1. We report a case of metastatic UC of the lung in a patient who had had a low-grade superficial UC of the urinary bladder and we discuss the cytopathological features of this rare entity in light of the literature. PMID:26229254

  19. Comparison of the selective targeting efficacy of Salmonella typhimurium A1-R and VNP20009 on the Lewis lung carcinoma in nude mice.

    PubMed

    Zhang, Yong; Zhang, Nan; Zhao, Ming; Hoffman, Robert M

    2015-06-10

    Salmonella typhimurium A1-R is auxotrophic for arg and leu, which attenuates growth in normal tissue but allows high tumor targeting and virulence. A1-R is effective against metastatic human prostate, breast, and pancreatic cancer as well as osteosarcoma, fibrosarcoma, and glioma in clinically-relevant mouse models. VNP20009 is also a genetically-modified strain of Salmonella typhimurium that has been tested in Phase I clinical trials, but is more attenuated than S. typhimurium A1-R and in addition of multiple amino-acid auxotrophs, is purine auxotropic with the purI mutation. In the present study, mouse Lewis lung carcinoma-bearing nude mouse models were treated with S. typhimurium A1-R or VNP20009. S. typhimurium A1-R and VNP20009 were both eliminated from the liver and spleen approximately 3-5 days after administration via the tail vein. However, A1-R showed higher tumor targeting and inhibited the Lewis lung carcinoma to a greater extent than VNP20009, with less body weight loss. The mice tolerated S. typhimurium A1-R to at a least 2-fold higher dose than VNP20009 when the bacteria were administered iv. The results of the present study suggest that S. typhimurium A1-R has greater clinical potential than VNP20009. PMID:25714030

  20. Apoptotic potential of C-phycoerythrin from Phormidium sp. A27DM and Halomicronema sp. A32DM on human lung carcinoma cells

    PubMed Central

    Madamwar, Datta; Patel, Dipak K; Desai, Swati N; Upadhyay, Kapil K; Devkar, Ranjitsinh V

    2015-01-01

    Phycobilisomes present in cyanobacteria are photosynthetic macromolecular protein complexes that are categorized into three types - phycoerythrins (high energy), phycocyanin (intermediate energy) and allophycocyanin (low energy). Structurally, they consist of α and β protein subunits and open chain tetrapyrrole prosthetic group (bilin chromophore), known for its antioxidant properties and therapeutic potential against a variety of physiological ailments. Phycoerythrins (C-PE) were purified from cyanobacterial strains Phormidium sp. A27DM and Halomicronema sp. A32DM and their respective apoptotic potentials were assessed on A549 human lung carcinoma cells. Both strains of cyanobacteria were cultured and the C-PE from each strain was extracted, quantified and characterized. C-PE accounted for a dose dependent decrement in cell viability, mitochondrial membrane potential and an increment in lactate dehydrogenase release. Higher doses of C-PE (of both strains) accounted for loss of cell viability and nuclear pycnosis. These findings were further substantiated with flow cytometry that revealed a cell arrest at G0/G1 phase and a high percentage of cells undergoing apoptosis following C-PE treatment. These results confirm the efficacy of C-PE from Phormidium sp. or Halomicronema sp. in triggering apoptotic cell death. This study is the first to report on apoptotic property of C-PE against A549 human lung carcinoma cells and warrants further studies to establish its anti-cancer potential. PMID:26535041

  1. Anti-ganglioside anti-idiotypic monoclonal antibody-based cancer vaccine induces apoptosis and antiangiogenic effect in a metastatic lung carcinoma.

    PubMed

    Diaz, Y; Gonzalez, A; Lopez, A; Perez, R; Vazquez, A M; Montero, E

    2009-07-01

    Anti-idiotype monoclonal antibody (mAb) 1E10 was generated by immunizing BALB/c mice with an Ab1 mAb which recognizes NeuGc-containing gangliosides, sulfatides and some tumor antigens. 1E10 mAb induces therapeutic effects in a primary breast carcinoma and a melanoma model. However, the tumor immunity mechanisms have not been elucidated. Here we show that aluminum hydroxide-precipitated 1E10 mAb immunization induced anti-metastatic effect in the 3LL-D122 Lewis Lung carcinoma, a poorly immunogenic and highly metastatic model in C57BL/6 mice. The therapeutic effect was associated to the increment of T cells infiltrating metastases, the reduction of new blood vessels formation and the increase of apoptotic tumor cells in lung nodules. Interestingly, active immunization does not induce measurable antibodies to the 1E10 mAb, the NeuGc-GM3 or tumor cells, which may suggest a different mechanism which has to be elucidated. These findings may support the relevance of this target for cancer biotherapy. PMID:19066887

  2. Downregulation of G3BPs inhibits the growth, migration and invasion of human lung carcinoma H1299 cells by suppressing the Src/FAK-associated signaling pathway.

    PubMed

    Zhang, H; Zhang, S-h; He, H-w; Zhang, C-x; Yu, D-k; Shao, R-g

    2013-11-01

    G3BP is a RasGAP binding protein that is overexpressed in many human cancers. We previously reported that downregulation of G3BP suppressed cell growth and induced apoptosis in HCT116 cells. Here we report that both transient and stable knockdown of G3BP suppressed the growth, migration and invasion capability of human lung carcinoma H1299 cells. Moreover, downregulation of G3BP significantly inhibited the phosphorylation of Src, FAK and ERK, and the levels of NF-κB were also markedly decreased in H1299 cells. Knockdown of G3BP also decreased the expression of matrix metalloproteinase-2 (MMP-2), MMP-9 and plasminogen activator (uPA), and in vivo data demonstrated that downregulation of G3BP markedly inhibited the growth of H1299 tumor xenografts. Together, these data revealed that knockdown of G3BP inhibited the migration and invasion of human lung carcinoma cells through the inhibition of Src, FAK, ERK and NF-κB and decreased levels of MMP-2, MMP-9 and uPA. PMID:24157923

  3. Screening for major driver oncogene alterations in adenosquamous lung carcinoma using PCR coupled with next-generation and Sanger sequencing methods

    PubMed Central

    Shi, Xiaohua; Wu, Huanwen; Lu, Junliang; Duan, Huanli; Liu, Xuguang; Liang, Zhiyong

    2016-01-01

    We investigated the frequency of major driver oncogenes in lung adenosquamous cell carcinoma (ASC) cases. Frequency of EGFR, K-Ras, B-Raf, PIK3CA, DDR2, ALK, and PDGFRA gene mutations was examined in 56 patients using next-generation sequencing, polymerase chain reaction, and Sanger sequencing. Macrodissection or microdissection was performed in 37 cases to separate the adenomatous and squamous components of ASC. The overall mutation rate was 64.29%, including 55.36%, 7.14%, and 1.79% for EGFR, K-Ras, and B-Raf mutations, respectively. PIK3CA mutation was detected in three cases; all involved coexisting EGFR mutations. Of the 37 cases, 34 were convergent in two components, while three showed EGFR mutations in the glandular components and three showed PIK3CA mutations in the squamous components. With respect to EGFR mutations, the number of young female patients, nonsmokers, and those with positive pleural invasion was higher in the mutation-positive group than that in the mutation-negative. K-Ras mutation was significantly associated with smoking. Overall survival in the different EGFR mutation groups differed significantly. The frequency and clinicopathological characteristics of EGFR- and K-Ras-mutated adenosquamous lung carcinoma were similar to that noted in Asian adenocarcinomas patients. The high convergence mutation rate in both adenomatous and squamous components suggests monoclonality in ASC. PMID:26923333

  4. Misonidazole combined with radiotherapy in the treatment of inoperable squamous cell carcinoma of the lung. A double-blind randomized trial

    SciTech Connect

    Panduro, J.; Kjaer, M.; Wolff-Jensen, J.; Hansen, H.H.

    1983-07-01

    Sixty-seven patients with inoperable squamous cell carcinoma of the lung were randomized to receive split-course irradiation therapy, 40 Gy in 10 fractions over 5 weeks plus either placebo or misonidazole 1.200 mg/m2 orally on each treatment day. The target area was the primary tumor, both hilar regions, mediastinum, and both supraclavicular regions. Thirty-three patients received misonidazole, while 34 patients received placebo. Mean observation time for the study was 27 months (range, 17-36+ months. 31% of the patients in the misonidazole group obtained a complete response (CR) or a partial response (PR) as compared to 29% in the placebo group. No difference was demonstrated in the relapse pattern comparing the two groups. The death intensity was significantly higher (P . 0.03) in the misonidazole than in the placebo group, with the median survival being 4.2 and 6.7 months, respectively. Eight patients in the misonidazole group (31%) developed sensoric neuropathy while one patient in the placebo group developed irradiation myelopathy of the Brown-Sequard type. The group of patients who later developed neuropathy had significantly higher plasma misonidazole concentrations on treatment days than the group of patients who did not. It is concluded that the combination of misonidazole and irradiation therapy for inoperable squamous cell carcinoma of the lung has no effect on response rate and relapse pattern, but a significant unexplained adverse effect on survival.

  5. Mechanisms of resistance to etoposide and teniposide in acquired resistant human colon and lung carcinoma cell lines.

    PubMed

    Long, B H; Wang, L; Lorico, A; Wang, R C; Brattain, M G; Casazza, A M

    1991-10-01

    Stable acquired resistance to etoposide (VP-16) or teniposide (VM-26) in HCT116 human colon carcinoma cells and A549 human lung adenocarcinoma cells, was previously obtained by weekly 1-h exposures to either drug (B. H. Long, Natl. Cancer Inst. Monogr., 4: 123-127, 1987). The purpose of this study was to identify possible mechanisms of resistance present in these cells by using human mdr1 and topoisomerase II DNA probes, antibodies to these gene products, and P4 phage unknotting assay for topoisomerase II activities. HCT116(VP)35 cells were 9-, 7-, and 6-fold resistant to VP-16, VM-26, and Adriamycin, respectively, and showed no cross-resistance to colchicine and actinomycin D. These cells had no differences in mdr1 gene, mdr1 mRNA, or P-glycoprotein levels but displayed decreased levels of topoisomerase II mRNA and enzyme activity without any alteration of drug sensitivity displayed by the enzyme. HCT116(VM)34 cells were 5-, 7-, and 21-fold resistant to VP-16, VM-26, and Adriamycin; were cross-resistant to colchicine (7-fold) and actinomycin D (18-fold); and possessed a 9-fold increase in mdr1 mRNA and increased P-glycoprotein without evidence of mdr1 gene amplification. No alterations in topoisomerase II gene or mRNA levels, enzyme activity, or drug sensitivity were observed. A549(VP)28 and A549(VM)28 cells were 8-fold resistant to VP-16 and VM-26 and 3-fold resistant to Adriamycin. Both lines were not cross-resistant to colchicine or actinomycin D but were hypersensitive to cis-platinum. No alterations in mdr1 gene, mdr1 mRNA, or P-glycoprotein levels, but lower topoisomerase II mRNA levels and decreased enzyme activities, were observed. Of the four acquired resistant cell lines, resistance is likely related to elevated mdr1 expression in one line and to decreased topoisomerase II expression in the other three lines. PMID:1717144

  6. Effect of c-ski overexpression on the development of cachexia in mice bearing the Lewis lung carcinoma.

    PubMed

    Carbó, Neus; Costelli, Paola; Busquets, Sílvia; López-Soriano, Joaquín; López-Soriano, Francisco J; Baccino, Francesco M; Argilés, Josep M

    2004-10-01

    Overexpression of the proto-oncogene c-ski in mice results in the development of a hypertrophic phenotype, characterized by increases in body and muscle weights. It has been previously shown in our laboratories that down-regulation of muscle protein breakdown associated with reduced expression of genes pertaining to different proteolytic systems likely account for this hypertrophic pattern. The aim of the present study was to evaluate the resistance of c-ski transgenic mice to catabolic stimuli such as those induced by the growth of the Lewis lung carcinoma. The tumor elicited a loss of body weight either in transgenic or in non-transgenic animals, although it was less pronounced in the former. The mass of gastrocnemius, tibialis and extensor digitorum longus (EDL) muscles were significantly reduced in non-transgenic tumor-bearing mice. Despite the anabolic setting displayed by the transgenic animals, the EDL only is completely protected against wasting. Indeed, gastrocnemius, tibialis and soleus show a reduction in weight, the latter two being significantly more depleted when compared to the non-transgenic tumor bearers. Similarly, the perigenital white adipose tissue presented a reduced mass which was more marked in the transgenic group. The quantitation of gene expression for ubiquitin, E2, C8 and calpain in the EDL showed marked differences between the transgenic and the non-transgenic groups of tumor hosts. As expected from previous results, in the latter group most of the transcripts examined increased with respect to controls as a consequence of tumor growth; by contrast, in the transgenic tumor hosts there was a significant reduction of ubiquitin, E2, C8 subunit, and calpain mRNA levels in comparison with the transgenic tumor-free animals. These results show that c-ski hyperexpression prevents tumor-induced muscle wasting in the EDL muscle, likely by impairing the state of activation of different proteolytic systems. However, the lack of effectiveness in

  7. Programmed death-1 ligand 1 and 2 are highly expressed in pleomorphic carcinomas of the lung: Comparison of sarcomatous and carcinomatous areas.

    PubMed

    Kim, Sehui; Kim, Moon-Young; Koh, Jaemoon; Go, Heounjeong; Lee, Dong Soo; Jeon, Yoon Kyung; Chung, Doo Hyun

    2015-11-01

    Pleomorphic carcinoma (PC) of the lung is a rare type of poorly differentiated non-small cell lung carcinoma (NSCLC) that belongs to sarcomatoid carcinoma (SC). It exhibits aggressive behaviour and resistance to chemotherapy and radiotherapy. Recently, immunotherapy targeting the programmed death-1 (PD-1)/PD ligand 1 (PD-L1) pathway has demonstrated favourable clinical outcomes in NSCLC. However, the expression patterns of PD-1-related molecules in pulmonary PC remain elusive. PD-L1 and PD-L2 expression was estimated in 41 cases of PC using immunohistochemistry. CD8(+) and PD-1(+) tumour-infiltrating lymphocytes (TILs) were also evaluated. PD-L1 and PD-L2 were highly expressed in pulmonary PCs (90.2% [37/41)]; 87.8% [36/41]). The amount of CD8(+) or PD-1(+) TILs and the ratio of PD-1(+)/CD8(+) TILs in PC were higher in males, smokers and older patients. PD-L1-positive PCs were infiltrated by higher numbers of CD8(+) TILs compared to PD-L1-negative cases (P=0.006). Of note, PD-L1 expression in pulmonary PCs was significantly higher in sarcomatous areas than in the carcinomatous portion (P=0.006). PC patients with a high ratio of PD-1(+)/CD8(+) TILs showed a shorter progression-free survival (P=0.036), whereas PD-L1 and PD-L2 expression had no prognostic implications. Our study demonstrates that pulmonary PCs very frequently express PD-L1 and PD-L2. Moreover, their expression is higher in sarcomatous cells than in carcinomatous areas. Thus, targeting the PD-1/PD-L1 pathway may represent a potential therapeutic candidate for this aggressive tumour. PMID:26329973

  8. Defining a standard set of patient-centred outcomes for lung cancer.

    PubMed

    Mak, Kimberley S; van Bommel, Annelotte C M; Stowell, Caleb; Abrahm, Janet L; Baker, Matthew; Baldotto, Clarissa S; Baldwin, David R; Borthwick, Diana; Carbone, David P; Chen, Aileen B; Fox, Jesme; Haswell, Tom; Koczywas, Marianna; Kozower, Benjamin D; Mehran, Reza J; Schramel, Franz M; Senan, Suresh; Stirling, Robert G; van Meerbeeck, Jan P; Wouters, Michel W J M; Peake, Michael D

    2016-09-01

    In lung cancer, outcome measurement has been mostly limited to survival. Proper assessment of the value of lung cancer treatments, and the performance of institutions delivering care, requires more comprehensive measurement of standardised outcomes.The International Consortium for Health Outcomes Measurement convened an international, multidisciplinary working group of patient representatives, medical oncologists, surgeons, radiation oncologists, pulmonologists, palliative care specialists, registry experts and specialist nurses to review existing data and practices. Using a modified Delphi method, the group developed a consensus recommendation ("the set") on the outcomes most essential to track for patients with lung cancer, along with baseline demographic, clinical and tumour characteristics (case-mix variables) for risk adjustment.The set applies to patients diagnosed with nonsmall cell lung cancer and small cell lung cancer. Our working group recommends the collection of the following outcomes: survival, complications during or within 6 months of treatment and patient-reported domains of health-related quality of life including pain, fatigue, cough and dyspnoea. Case-mix variables were defined to improve interpretation of comparisons.We defined an international consensus recommendation of the most important outcomes for lung cancer patients, along with relevant case-mix variables, and are working to support adoption and reporting of these measures globally. PMID:27390281

  9. Defining a standard set of patient-centred outcomes for lung cancer

    PubMed Central

    van Bommel, Annelotte C.M.; Stowell, Caleb; Abrahm, Janet L.; Baker, Matthew; Baldotto, Clarissa S.; Baldwin, David R.; Borthwick, Diana; Carbone, David P.; Chen, Aileen B.; Fox, Jesme; Haswell, Tom; Koczywas, Marianna; Kozower, Benjamin D.; Mehran, Reza J.; Schramel, Franz M.; Senan, Suresh; Stirling, Robert G.; van Meerbeeck, Jan P.; Wouters, Michel W.J.M.

    2016-01-01

    In lung cancer, outcome measurement has been mostly limited to survival. Proper assessment of the value of lung cancer treatments, and the performance of institutions delivering care, requires more comprehensive measurement of standardised outcomes. The International Consortium for Health Outcomes Measurement convened an international, multidisciplinary working group of patient representatives, medical oncologists, surgeons, radiation oncologists, pulmonologists, palliative care specialists, registry experts and specialist nurses to review existing data and practices. Using a modified Delphi method, the group developed a consensus recommendation (“the set”) on the outcomes most essential to track for patients with lung cancer, along with baseline demographic, clinical and tumour characteristics (case-mix variables) for risk adjustment. The set applies to patients diagnosed with nonsmall cell lung cancer and small cell lung cancer. Our working group recommends the collection of the following outcomes: survival, complications during or within 6 months of treatment and patient-reported domains of health-related quality of life including pain, fatigue, cough and dyspnoea. Case-mix variables were defined to improve interpretation of comparisons. We defined an international consensus recommendation of the most important outcomes for lung cancer patients, along with relevant case-mix variables, and are working to support adoption and reporting of these measures globally. PMID:27390281

  10. The role of Rac1 in the regulation of NF-kB activity, cell proliferation, and cell migration in non-small cell lung carcinoma

    PubMed Central

    Gastonguay, Adam; Berg, Tracy; Hauser, Andrew D.; Schuld, Nathan; Lorimer, Ellen; Williams, Carol L.

    2012-01-01

    The small GTPase Rac1 regulates many cellular processes, including cytoskeletal reorganization, cell migration, proliferation, and survival. Additionally, Rac1 plays a major role in activating NF-κB-mediated transcription. Both Rac1 and NF-κB regulate many properties of the malignant phenotype, including anchorage-independent proliferation and survival, metastasis, and angiogenesis. Despite these findings, the roles of Rac1and NF-κB in non-small cell lung carcinoma, a leading cause of cancer deaths, have not been thoroughly investigated. Here, we compared the effects of Rac1 siRNA to that of the Rac1 inhibitor NSC23766 on multiple features of the NSCLC malignant phenotype, including NF-κB activity. We show that the siRNA-mediated silencing of Rac1 in lung cancer cells results in decreased cell proliferation and migration. The decrease in proliferation was observed in both anchorage-dependent and anchorage-independent assays. Furthermore, cells with decreased Rac1 expression have a slowed progression through the G1 phase of the cell cycle. These effects induced by Rac1 siRNA correlated with a decrease in NF-κB transcriptional activity. Additionally, inhibition of NF-κB signaling with BAY 11–7082 inhibited proliferation; indicating that the loss of cell proliferation and migration induced by the silencing of Rac1 expression may be attributed in part to loss of NF-κB activity. Interestingly, treatment with the Rac1 inhibitor NSC23766 strongly inhibits cell proliferation, cell cycle progression, and NF-κB activity in lung cancer cells, to an even greater extent than the inhibition induced by Rac1 siRNA. These findings indicate that Rac1 plays an important role in lung cancer cell proliferation and migration, most likely through its ability to promote NF-κB activity, and highlight Rac1 pathways as therapeutic targets for the treatment of lung cancer. PMID:22549160

  11. CCTα is a novel antigen detected by the anti-ERCC1 antibody 8F1 with biomarker value in lung and head and neck squamous cell carcinomas

    PubMed Central

    Vaezi, Alec; Bepler, Gerold; Bhagwat, Nikhil; Malysa, Agnes; Rubatt, Jennifer; Chen, Wei; Hood, Brian; Conrads, Thomas; Wang, Lin; Kemp, Carolyn; Niedernhofer, Laura J.

    2014-01-01

    BACKGROUND Determination of in situ protein levels of ERCC1 with the antibody (8F1) is prognostic of survival in non-small-cell lung cancer (NSCLC). We previously demonstrated that 8F1 recognizes a second nuclear antigen. We identified this antigen and analyzed its value as a biomarker of clinical outcomes. METHODS The second antigen was identified by mass spectrometry. Protein identity and antibody specificity were confirmed through knockdown and overexpression experiments. Immunohistochemistry (IHC) of 187 early stage NSCLC samples and 60 head and neck squamous cell carcinomas (HNSCC) was used to examine the influence of the second antigen on 8F1 immunoreactivity and association with patient outcomes. RESULTS Cholinephosphate citidylyl transferase–α (CCTα, a.k.a. phosphate citidylyl transferase 1 choline alpha (PCYT1A), a phospholipid synthesis enzyme regulated by RAS, is the second antigen of 8F1. In NSCLC, CCTα contributed (rho = 0.38) to 8F1 immunoreactivity. In squamous cell carcinoma of the lung, CCTα was the dominant determinant of 8F1 immunoreactivity, while its contribution in other subtypes of lung cancer was negligible. High expression of CCTα, but not ERCC1, was prognostic of longer disease-free (log-rank p = 0.002), and overall survival (log-rank p = 0.056). Similarly, in HNSCC, CCTα contributed strongly to 8F1 immunoreactivity (rho = 0.74), and high CCTα expression was prognostic of survival (log-rank p = 0.022 for DFS and p = 0.027 for OS). CONCLUSIONS CCTα is the second antigen detected by 8F1. High CCTα expression is prognostic of survival in NSCLC treated by surgery alone and HNSCC. CCTα is a promising biomarker of patient survival and deserves further study. PMID:24692084

  12. RNA-Seq analysis for the potential targets and molecular mechanisms of 17 β-estradiol in squamous cell lung carcinoma.

    PubMed

    Chen, X; Wu, R; Wang, S; Duan, Q; Xuan, Y

    2016-01-01

    The efficacy of 17 β-estradiol (E2) was valid in some cancers, while its effects on squamous cell lung carcinoma (SCLC) were still unclear. The aim of our study was to investigate the potential targets and molecular mechanisms of E2 in SCLC cells.Two RNA libraries from human lung carcinoma cells (SK-MES-1) with and without E2 treatment were constructed and sequenced. The differentially expressed genes (DEGs) between cells with or without E2 treatment were identified by cuffdiff software. Hierarchical Clustering Analysis (HCA) was performed for displaying gene expression changes and classification. Furthermore, enrichment analyses of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology Biological Process (GO BP) terms were performed through DAVID. The protein-protein interaction (PPI) network was constructed through STRING. Additionally, differentially expressed lncRNAs were also selected by cuffdiff software.Total 129 DEGs including 58 up- and 71 down- regulated genes were obtained. Cancer-related pathways including small cell lung cancer, hypertrophic cardiomyopathy (HCM) and pathways in cancer and biological processes including regulation of phosphorus metabolic process, protein localization and nucleus organization were enriched. The PPI network with 113 nodes and 312 edges was constructed. CASP3, ITGA2, COL4A6, PML and CDC25B were identified as hub nodes which had more interactions with others in the PPI network. Furthermore, eight up-regulated and ten down-regulated lncRNAs were selected.CASP3, ITGA2 and Lnc-DLK1-4:31 (one of down-regulated lncRNAs) might play pivotal roles in E2 treated SCNC cells by influencing cell apoptosis, angiogenesis and cell invasion respectively. PMID:26952511

  13. Terameprocol (tetra-O-methyl nordihydroguaiaretic acid), an inhibitor of Sp1-mediated survivin transcription, induces radiosensitization in non-small cell lung carcinoma

    PubMed Central

    Sun, Yunguang; Giacalone, Nicholas J.; Lu, Bo

    2010-01-01

    Introduction Survivin, an inhibitor of apoptosis protein (IAP) and key regulator of mitosis, is up-regulated in a variety of cancers and is often associated with a worse prognosis. Terameprocol down-regulates the Sp1-mediated transcription of survivin and Cdk1, which is important for cell cycle progression, as well as many other proteins. Survivin inhibition has previously been shown to result in the induction of apoptosis and radiosensitization. Methods This study examined the effects of terameprocol administration on survivin transcription and expression in HCC2429 and H460 lung cancer cells. We also examined the combined effects of radiation and terameprocol on apoptosis and radiosensitivity. Results Using immunoblot analysis and luciferase assays, we confirmed that terameprocol decreases survivin transcription and protein expression. Ultimately, however, decreases in survivin expression failed to correlate with an increase in apoptosis. Nonetheless, clonogenic assay revealed that terameprocol induces increased radiosensitization in HCC2429 (DER = 1.26, p = 0.019) and H460 (DER = 1.18, p = 0.001) cells. Additionally, the data show no effect of terameprocol on cell cycle in either HCC2429 or H460 cells. Conclusions Terameprocol significantly enhances the sensitivity of non-small cell lung carcinoma cell lines to radiation therapy, although the mechanism of action remains unclear. Further study is warranted to assess the potential of terameprocol as an agent that may enhance the therapeutic ratio of radiotherapy in lung cancer. PMID:21107289

  14. [Complete Surgical Resection of a Huge Hepatocellular Carcinoma Invading the Diaphragm and Lung after Transcatheter Arterial Chemoembolization (TACE) and Sorafenib--A Case Report].

    PubMed

    Mukai, Yosuke; Wada, Hiroshi; Eguchi, Hidetoshi; Tomokuni, Akira; Tomimaru, Yoshito; Asaoka, Tadafumi; Kawamoto, Koichi; Marubashi, Shigeru; Umeshita, Koji; Doki, Yuichiro; Mori, Masaki; Nagano, Hiroaki

    2015-11-01

    We report a case of locally advanced huge hepatocellular carcinoma (HCC) invading the diaphragm and the right lung, which was controlled by sorafenib, thereby allowing curative resection. A 72-year-old man was diagnosed with advanced HCC invading the diaphragm and the right lung. At the time of diagnosis, his tumor was considered unresectable and he underwent transarterial embolization (TAE)/transcatheter arterial chemoembolization (TACE) 3 times. Assessment with enhanced CT after TAE/TACE showed that a viable lesion remained. Subsequently, he was treated with sorafenib for 15 months. Reassessment showed that the main tumor remained stable in size, and he was admitted to our hospital for surgery. Preoperative evaluation by enhanced CT and MRI detected an intrahepatic metastasis in segment 4 of the liver. After TACE was performed for this nodule, extended right hemihepatectomy with right diaphragmatic and right lung partial resection was performed. He had no postoperative complications and was discharged 27 days after surgery. He remains alive without recurrence 10 months after surgery. PMID:26805122

  15. Multicenter Phase II Study of Nedaplatin and Irinotecan for Patients with Squamous Cell Carcinoma of the Lung: Thoracic Oncology Research Group 0910.

    PubMed

    Yamada, Kouzo; Saito, Haruhiro; Kondo, Tetsuro; Murakami, Shuji; Masuda, Noriyuki; Yamamoto, Michiko; Igawa, Satoshi; Katono, Ken; Takiguchi, Yuichi; Iwasawa, Shunichiro; Kurimoto, Ryota; Okamoto, Hiroaki; Shimokawa, Tsuneo; Hosomi, Yukio; Takagi, Yusuke; Kishi, Kazuma; Ohba, Mari; Oshita, Fumihiro; Watanabe, Koshiro

    2015-12-01

    Squamous cell carcinoma (SCC) of the lung is moderately responsive to anticancer drugs, but no specific chemotherapy regimens have yet been established. We conducted a multicenter phase II study of nedaplatin (NP) and irinotecan (CPT) for SCC of the lung. Fifty patients underwent 4 to 6 cycles of chemotherapy comprising of NP at 100 mg/m(2) on day 1 and CPT at 60 mg/m(2) on days 1 and 8 every 4 weeks. Twenty-seven patients received 4 to 6 cycles of chemotherapy (median=4 cycles). Major toxicities included neutropenia (46.0%), grade 3 or 4 anorexia (22.0%), febrile neutropenia (16.0%), diarrhea (12.0%), hyponatremia (12.0%), grade 4 anemia (10.0%), thrombocytopenia (10.0%) and infection (10.0%). There were no treatment-related deaths. One patient achieved a complete response and 16 a partial response, with an overall response rate of 34.0%. The median survival time was 11.8 months (95% CI=8.3-15.8 months) and the 2-year survival rate was 22.0%. In conclusion, the NP and CPT regimen is not recommend for further evaluation for patients with advanced SCC of the lung. PMID:26637886

  16. A Series of α-Amino Acid Ester Prodrugs of Camptothecin: In vitro Hydrolysis and A549 Human Lung Carcinoma Cell Cytotoxicity

    PubMed Central

    Deshmukh, Manjeet; Chao, Piyun; Kutscher, Hilliard L.; Gao, Dayuan; Sinko, Patrick J.

    2013-01-01

    The objective of the present study was to identify a camptothecin (CPT) prodrug with optimal release and cytotoxicity properties for immobilization on a passively targeted microparticle delivery system. A series of α-amino acid ester prodrugs of CPT were synthesized, characterized and evaluated. Four CPT prodrugs were synthesized with increasing aliphatic chain length (glycine (Gly) (2a), alanine (Ala) (2b), aminobutyric acid (Abu) (2c) and norvaline (Nva) (2d)). Prodrug reconversion was studied at pH 6.6, 7.0 and 7.4 corresponding to tumor, lung and extracellular/physiological pH, respectively. Cytotoxicity was evaluated in A549 human lung carcinoma cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The hydrolytic reconversion rate to parent CPT increased with decreasing side chain length as well as increasing pH. The Hill slope of 2d was significantly less than CPT and the other prodrugs tested, indicating a higher cell death rate at lower concentrations. These results suggest that 2d is the best candidate for a passively targeted sustained release lung delivery system. PMID:20063889

  17. Ultrasound of extravascular lung water: a new standard for pulmonary congestion.

    PubMed

    Picano, Eugenio; Pellikka, Patricia A

    2016-07-14

    Extravascular lung water (EVLW) is a key variable in heart failure management and prognosis, but its objective assessment remains elusive. Lung imaging has been traditionally considered off-limits for ultrasound techniques due to the acoustic barrier of high-impedance air wall. In pulmonary congestion however, the presence of both air and water creates a peculiar echo fingerprint. Lung ultrasound shows B-lines, comet-like signals arising from a hyper-echoic pleural line with a to-and-fro movement synchronized with respiration. Increasing EVLW accumulation changes the normal, no-echo signal (black lung, no EVLW) into a black-and-white pattern (interstitial sub-pleural oedema with multiple B-lines) or a white lung pattern (alveolar pulmonary oedema) with coalescing B-lines. The number and spatial extent of B-lines on the antero-lateral chest allows a semi-quantitative estimation of EVLW (from absent, ≤5, to severe pulmonary oedema, >30 B-lines). Wet B-lines are made by water and decreased by diuretics, which cannot modify dry B-lines made by connective tissue. B-lines can be evaluated anywhere (including extreme environmental conditions with pocket size instruments to detect high-altitude pulmonary oedema), anytime (during dialysis to titrate intervention), by anyone (even a novice sonographer after 1 h training), and on anybody (since the chest acoustic window usually remains patent when echocardiography is not feasible). Cardiologists can achieve much diagnostic gain with little investment of technology, training, and time. B-lines represent 'the shape of lung water'. They allow non-invasive detection, in real time, of even sub-clinical forms of pulmonary oedema with a low cost, radiation-free approach. PMID:27174289

  18. Ultrasound of extravascular lung water: a new standard for pulmonary congestion

    PubMed Central

    Picano, Eugenio; Pellikka, Patricia A.

    2016-01-01

    Extravascular lung water (EVLW) is a key variable in heart failure management and prognosis, but its objective assessment remains elusive. Lung imaging has been traditionally considered off-limits for ultrasound techniques due to the acoustic barrier of high-impedance air wall. In pulmonary congestion however, the presence of both air and water creates a peculiar echo fingerprint. Lung ultrasound shows B-lines, comet-like signals arising from a hyper-echoic pleural line with a to-and-fro movement synchronized with respiration. Increasing EVLW accumulation changes the normal, no-echo signal (black lung, no EVLW) into a black-and-white pattern (interstitial sub-pleural oedema with multiple B-lines) or a white lung pattern (alveolar pulmonary oedema) with coalescing B-lines. The number and spatial extent of B-lines on the antero-lateral chest allows a semi-quantitative estimation of EVLW (from absent, ≤5, to severe pulmonary oedema, >30 B-lines). Wet B-lines are made by water and decreased by diuretics, which cannot modify dry B-lines made by connective tissue. B-lines can be evaluated anywhere (including extreme environmental conditions with pocket size instruments to detect high-altitude pulmonary oedema), anytime (during dialysis to titrate intervention), by anyone (even a novice sonographer after 1 h training), and on anybody (since the chest acoustic window usually remains patent when echocardiography is not feasible). Cardiologists can achieve much diagnostic gain with little investment of technology, training, and time. B-lines represent ‘the shape of lung water’. They allow non-invasive detection, in real time, of even sub-clinical forms of pulmonary oedema with a low cost, radiation-free approach. PMID:27174289

  19. K-RAS MUTATIONS IN LUNG CARCINOMAS FROM NONSMOKING WOMEN EXPOSED TO UNVENTED COAL SMOKE IN CHINA

    EPA Science Inventory

    Abstract Lung cancer mortality rate in nonsmoking women in Xuan Wei (XW) County is the highest in China. The XW lung cancer rate is associated with exposure to coal smoke, containing high concentrations of polycyclic aromatic hydrocarbons (PARs), in unvented homes. Here we restig...

  20. Systems for Lung Volume Standardization during Static and Dynamic MDCT-based Quantitative Assessment of Pulmonary Structure and Function

    PubMed Central

    Fuld, Matthew K.; Grout, Randall; Guo, Junfeng; Morgan, John H.; Hoffman, Eric A.

    2013-01-01

    Rationale and Objectives Multidetector-row Computed Tomography (MDCT) has emerged as a tool for quantitative assessment of parenchymal destruction, air trapping (density metrics) and airway remodeling (metrics relating airway wall and lumen geometry) in chronic obstructive pulmonary disease (COPD) and asthma. Critical to the accuracy and interpretability of these MDCT-derived metrics is the assurance that the lungs are scanned during a breath-hold at a standardized volume. Materials and Methods A computer monitored turbine-based flow meter system was developed to control patient breath-holds and facilitate static imaging at fixed percentages of the vital capacity. Due to calibration challenges with gas density changes during multi-breath xenon-CT an alternative system was required. The design incorporated dual rolling seal pistons. Both systems were tested in a laboratory environment and human subject trials. Results The turbine-based system successfully controlled lung volumes in 32/37 subjects, having a linear relationship for CT measured air volume between repeated scans: for all scans, the mean and confidence interval of the differences (scan1-scan2) was −9 ml (−169, 151); for TLC alone 6 ml (−164, 177); for FRC alone, −23 ml (−172, 126). The dual-piston system successfully controlled lung volume in 31/41 subjects. Study failures related largely to subject non-compliance with verbal instruction and gas leaks around the mouthpiece. Conclusion We demonstrate the successful use of a turbine-based system for static lung volume control and demonstrate its inadequacies for dynamic xenon-CT studies. Implementation of a dual-rolling seal spirometer has been shown to adequately control lung volume for multi-breath wash-in xenon-CT studies. These systems coupled with proper patient coaching provide the tools for the use of CT to quantitate regional lung structure and function. The wash-in xenon-CT method for assessing regional lung function, while not

  1. A Dual Role for KRT81: A miR-SNP Associated with Recurrence in Non-Small-Cell Lung Cancer and a Novel Marker of Squamous Cell Lung Carcinoma

    PubMed Central

    Campayo, Marc; Navarro, Alfons; Viñolas, Nuria; Tejero, Rut; Muñoz, Carmen; Diaz, Tania; Marrades, Ramon; Cabanas, Maria L.; Gimferrer, Josep M.; Gascon, Pere; Ramirez, Jose; Monzo, Mariano

    2011-01-01

    MicroRNAs (miRNAs) play an important role in carcinogenesis through the regulation of their target genes. miRNA-related single nucleotide polymorphisms (miR-SNPs) can affect miRNA biogenesis and target sites and can alter microRNA expression and functions. We examined 11 miR-SNPs, including 5 in microRNA genes, 3 in microRNA binding sites and 3 in microRNA-processing machinery components, and evaluated time to recurrence (TTR) according to miR-SNP genotypes in 175 surgically resected non-small-cell lung cancer (NSCLC) patients. Significant differences in TTR were found according to KRT81 rs3660 (median TTR: 20.3 months for the CC genotype versus 86.8 months for the CG or GG genotype; P = 0.003) and XPO5 rs11077 (median TTR: 24.7 months for the AA genotype versus 73.1 months for the AC or CC genotypes; P = 0.029). Moreover, when patients were divided according to stage, these differences were maintained for stage I patients (P = 0.002 for KRT81 rs3660; P<0.001 for XPO5 rs11077). When patients were divided into sub-groups according to histology, the effect of the KRT81 rs3660 genotype on TTR was significant in patients with squamous cell carcinoma (P = 0.004) but not in those with adenocarcinoma. In the multivariate analyses, the KRT81 rs3660 CC genotype (OR = 1.8; P = 0.023) and the XPO5 rs11077 AA genotype (OR = 1.77; P = 0.026) emerged as independent variables influencing TTR. Immunohistochemical analyses in 80 lung specimens showed that 95% of squamous cell carcinomas were positive for KRT81, compared to only 19% of adenocarcinomas (P<0.0001). In conclusion, miR-SNPs are a novel class of SNPs that can add useful prognostic information on the clinical outcome of resected NSCLC patients and may be a potential key tool for selecting high-risk stage I patients. Moreover, KRT81 has emerged as a promising immunohistochemical marker for the identification of squamous cell lung carcinoma. PMID:21799879

  2. Is the shape of the decline in risk following quitting smoking similar for squamous cell carcinoma and adenocarcinoma of the lung? A quantitative review using the negative exponential model.

    PubMed

    Fry, John S; Lee, Peter N; Forey, Barbara A; Coombs, Katharine J

    2015-06-01

    One possible contributor to the reported rise in the ratio of adenocarcinoma to squamous cell carcinoma of the lung may be differences in the pattern of decline in risk following quitting for the two lung cancer types. Earlier, using data from 85 studies comparing overall lung cancer risks in current smokers, quitters (by time quit) and never smokers, we fitted the negative exponential model, deriving an estimate of 9.93years for the half-life - the time when the excess risk for quitters compared to never smokers becomes half that for continuing smokers. Here we applied the same techniques to data from 16 studies providing RRs specific for lung cancer type. From the 13 studies where the half-life was estimable for each type, we derived estimates of 11.68 (95% CI 10.22-13.34) for squamous cell carcinoma and 14.45 (11.92-17.52) for adenocarcinoma. The ratio of the half-lives was estimated as 1.32 (95% CI 1.20-1.46, p<0.001). The slower decline in quitters for adenocarcinoma, evident in subgroups by sex, age and other factors, may be one of the factors contributing to the reported rise in the ratio of adenocarcinoma to squamous cell carcinoma. Others include changes in the diagnosis and classification of lung cancer. PMID:25703436

  3. Trial Comparing the Use of FLT PET to Standard CT to Assess Treatment Response of Neoadjuvant Docetaxel and Cisplatin in Stage IB-IIIA Resectable NSCLC

    ClinicalTrials.gov

    2015-04-30

    Recurrent Non-Small Cell Lung Carcinoma; Stage IB Non-Small Cell Lung Carcinoma; Stage IIA Non-Small Cell Lung Carcinoma; Stage IIB Non-Small Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IV Non-Small Cell Lung Cancer

  4. Expression of Tumor-Derived Vascular Endothelial Growth Factor and Its Receptors Is Associated With Outcome in Early Squamous Cell Carcinoma of the Lung

    PubMed Central

    Pajares, María J.; Agorreta, Jackeline; Larrayoz, Marta; Vesin, Aurélien; Ezponda, Teresa; Zudaire, Isabel; Torre, Wenceslao; Lozano, María D.; Brambilla, Elisabeth; Brambilla, Christian; Wistuba, Ignacio I.; Behrens, Carmen; Timsit, Jean-Francois; Pio, Ruben; Field, John K.; Montuenga, Luis M.

    2012-01-01

    Purpose Antiangiogenic therapies targeting the vascular endothelial growth factor (VEGF) pathway have yielded more modest clinical benefit to patients with non–small-cell lung cancer (NSCLC) than initially expected. Clinical data suggest a distinct biologic role of the VEGF pathway in the different histologic subtypes of lung cancer. To clarify the influence of histologic differentiation in the prognostic relevance of VEGF-mediated signaling in NSCLC, we performed a concomitant analysis of the expression of three key elements of the VEGF pathway in the earliest stages of the following two principal histologic subtypes: squamous cell carcinoma (SCC) and adenocarcinoma (ADC). Patients and Methods We evaluated tumor cell expression of VEGF, VEGF receptor (VEGFR) 1, and VEGFR2 using automatic immunostaining in a series of 298 patients with early-stage NSCLC recruited as part of the multicenter European Early Lung Cancer Detection Group project. A score measuring the VEGF signaling pathway was calculated by adding the tumor cell expression value of VEGF and its two receptors. The results were validated in two additional independent cohorts of patients with NSCLC. Results The combination of high VEGF, VEGFR1, and VEGFR2 protein expression was associated with lower risk of disease progression in early SCC (univariate analysis, P = .008; multivariate analysis, hazard ratio, 0.62; 95% CI, 0.42 to 0.92; P = .02). The results were validated in two independent patient cohorts, confirming the favorable prognostic value of high VEGF signaling score in early lung SCC. Conclusion Our results clearly indicate that the combination of high expression of the three key elements in the VEGF pathway is associated with a good prognosis in patients with early SCC but not in patients with ADC. PMID:22355056

  5. Tobacco carcinogen induces both lung cancer and non-alcoholic steatohepatitis and hepatocellular carcinomas in ferrets which can be attenuated by lycopene supplementation.

    PubMed

    Aizawa, Koichi; Liu, Chun; Tang, Sanyuan; Veeramachaneni, Sudipta; Hu, Kang-Quan; Smith, Donald E; Wang, Xiang-Dong

    2016-09-01

    Early epidemiologic studies have reported that tobacco smoking, which is causally associated with liver cancer, is an independent risk factor for non-alcoholic fatty liver diseases (NAFLD). Lycopene from tomatoes has been shown to be a potential preventive agent against NAFLD and hepatocellular carcinoma (HCC). In the present study, we investigated whether the tobacco carcinogen 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induces lesions in both lungs and livers of ferrets with or without lycopene intervention. Male ferrets (6 groups, n = 8-10) were treated either with NNK (50 mg/kg BW, i.p., once a month for four consecutive months) or saline with or without dietary lycopene supplementation (2.2 and 6.6 mg/kg BW/day, respectively) for 26 weeks. Results demonstrate that NNK exposure results in higher incidences of lung tumors, HCC and steatohepatitis (which is characterized by severe inflammatory cell infiltration with concurrent fat accumulation in liver, hepatocellular ballooning degeneration and increased NF-κB expression), as well as elevations in bilirubin and AST levels in ferrets. Lycopene supplementation at two doses prevented NNK-induced expressions of α7 nicotinic acetylcholine receptor in the lung and NF-κB and CYP2E1 in the liver and attenuated the NNK-induced mortality and pathological lesions in both the lungs and livers of ferrets. The present study provided strong experimental evidence that the tobacco carcinogen NNK can induce both HCC and steatohepatitis in the ferrets and can be a useful model for studying tobacco carcinogen-associated NAFLD and liver cancer. Furthermore, lycopene could provide potential benefits against smoke carcinogen-induced pulmonary and hepatic injury. PMID:27116542

  6. Detection of Urothelial Carcinoma: Comparison of Reduced-Dose Iterative Reconstruction with Standard-Dose Filtered Back Projection.

    PubMed

    Bahn, Young Eun; Kim, See Hyung; Kim, Mi Jeong; Kim, Chan Sun; Kim, Young Hwan; Cho, Seung Hyun

    2016-05-01

    Purpose To prospectively assess radiation dose, image quality, and diagnostic performance of computed tomography (CT) urography for detection of urothelial carcinomas by performing reduced-dose scanning with iterative reconstruction (IR) compared with standard-dose scanning with filtered back projection (FBP). Materials and Methods The institutional review board approved the study with written informed patient consent. In total, 2163 patients at high risk for urothelial carcinomas randomly underwent standard-dose scanning with FBP (protocol A, 120 kVp for >80 kg body weight; protocol B, 100 kVp for 50-80 kg body weight) or reduced-dose scanning with IR (protocol C, 100 kVp for >80 kg body weight; protocol D, 80 kVp for 50-80 kg body weight). Objective image quality (signal-to-noise ratio and contrast-to-noise ratio) between the two groups with same weight range was measured for various regions of interest. Subjective image quality (visual image noise, artifact, ureter depiction, and overall image quality) and diagnostic accuracy (per lesion and per patient) were assessed with three- and five-point scores, respectively. Results Size-specific dose estimate (protocol A vs protocol C, 24.2 mGy vs 19.2 mGy, respectively; protocol B vs protocol D,13.9 mGy vs 8.8 mGy, respectively) was significantly lower in reduced-dose scanning (P < .001 for both). There were significantly higher signal-to-noise and contrast-to-noise ratios in reduced-dose scanning, except for the abdominal aorta (P < .05 for all). There was no significant difference in subjective image quality, except for artifacts in protocols B and D (range, 4-5 vs 3-4; P < .05). Per-lesion diagnostic accuracy was 90.8% (89 of 98, protocol A), 91.3% (105 of 115, protocol B), 92.9% (79 of 85, protocol C), and 88.8% (111 of 125, protocol D). Conclusion Reduced-dose scanning with IR showed dose reduction and no significant difference of image quality in detection of urothelial carcinomas, except for some artifacts in 80

  7. Lobar lung resection in elderly patients with non-small cell lung carcinoma: impact of chronic obstructive pulmonary disease on surgical outcome.

    PubMed

    Senbaklavaci, O

    2014-01-01

    The aim of this study was to evaluate the impact of chronic obstructive pulmonary disease (COPD) on the perioperative morbidity and mortality after lobar lung resection for non-small cell lung cancer (NSCLC) in patients aged 70 years and older. The medical records of 73 patients≥70 years who underwent lobar lung resection for NSCLC from 2003 to 2013 at our department were reviewed retrospectively. There were 27 patients with a mean age of 73.6 years and mean predicted forced expiratory volume in 1 s (FEV1) of 69.7% in the COPD group whereas remaining 46 patients (mean age=75.6 years) in the non-COPD group had a mean predicted FEV1 of 79.1%. There were no significant differences in perioperative morbidity (4.8% in the COPD group versus 17.4% in the non-COPD group) between both groups. We had no perioperative mortality in both groups. Lobar lung resection for NSCLC seems to be a safe therapy option for elderly patients with COPD who are fulfilling the common functional criteria of operability so that radical surgery should remain the mainstay of treatment for early-stage NSCLC in this increasing subpopulation. PMID:25058759

  8. Separation of an aqueous extract Inonotus obliquus (Chaga). A novel look at the efficiency of its influence on proliferation of A549 human lung carcinoma cells.

    PubMed

    Mazurkiewicz, Witold; Rydel, Katarzyna; Pogocki, Dariusz; Lemieszek, Marta Kinga; Langner, Ewa; Rzeski, Wojciech

    2010-01-01

    Aqueous extract of Inonotus obliquus was hydrolyzed in dilute hydrochloric acid. The products were extracted applying organic solvents, and separated chromatographically on a silica gel-packed column. Eluted fractions were analyzed by means of GC-MS. The presence of hydrocarbons, alcohols, phenols and various carbonyl compounds in analyzed fractions has been detected and quantified. Preliminarily experiments on the influence of certain separated samples on the proliferation of A549 human lung carcinoma cells were performed. Therefore, we hypothesize that the major antiproliferative effects are related to the presence of benzaldehyde, which is a benzyl alcohol metabolite formed in situ in the cells culture with the yield moderated by the presence of trace amounts of "high molecular mass compounds". PMID:20635536

  9. The PRKCI and SOX2 Oncogenes are Co-amplified and Cooperate to Activate Hedgehog Signaling in Lung Squamous Cell Carcinoma

    PubMed Central

    Justilien, Verline; Walsh, Michael P.; Ali, Syed A.; Thompson, E. Aubrey; Murray, Nicole R.; Fields, Alan P.

    2014-01-01

    SUMMARY We report that two oncogenes co-amplified on chromosome 3q26, PRKCI and SOX2, cooperate to drive a stem-like phenotype in lung squamous cell carcinoma (LSCC). PKCι phosphorylates SOX2, a master transcriptional regulator of stemness, and recruits it to the promoter of Hedgehog Acyl Transferase (HHAT), which catalyzes the rate-limiting step in Hh ligand production. PKCι-mediated SOX2 phosphorylation is required for HHAT promoter occupancy, HHAT expression, and maintenance of a stem-like phenotype. Primary LSCC tumors coordinately overexpress PKCι, SOX2, and HHAT, and require PKCι-SOX2-HHAT signaling to maintain a stem-like phenotype. Thus, PKCι and SOX2 are genetically, biochemically and functionally linked in LSCC, and together they drive tumorigenesis by establishing a cell autonomous Hh signaling axis. PMID:24525231

  10. Ochratoxin A and T-2 Toxin Induce Clonogenicity and Cell Migration in Human Colon Carcinoma and Fetal Lung Fibroblast Cell Lines.

    PubMed

    Abassi, Haila; Ayed-Boussema, Imen; Shirley, Sarah; Abid, Salwa; Bacha, Hassen

    2016-03-01

    T-2 toxin and Ochratoxin A (OTA) are toxic secondary metabolites produced by various fungi, and together they contaminate feedstuffs worldwide. T-2 toxin and OTA may exert carcinogenic action in rodent. Despite the various in vivo experiments, carcinogenicity of these two mycotoxins has not yet been proven for human. In this current study, we proposed to investigate, in Human colon carcinoma cells and fetal lung fibroblast-like cells transfected with MYC, the effect of T-2 toxin and OTA on cell clonogenicity and cell migration. Results of the present investigation showed that T2-toxin as well as OTA has an important clonogenic effect in all cell lines, suggesting that these mycotoxins could promote the transcription of c-myc gene. Furthermore, T-2 toxin and OTA enhanced the migration effect of HCT116 cells at very low concentrations, proposing that these mycotoxins may exhibit carcinogenesis-like properties in the studied cells. PMID:26849850

  11. [A case of limbic encephalitis with small cell lung carcinoma in which the cognitive function improved and redeteriorated during tumor therapy].

    PubMed

    Fujimoto, So; Yamaguchi, Yasuhiro; Gotanda, Hiroshi; Shiozawa, Ryosuke; Takemura, Aya; Umeda-Kameyama, Yumi; Yamamoto, Hiroshi; Iijima, Katsuya; Akishita, Masahiro; Ouchi, Yasuyoshi

    2010-01-01

    We report the findings regarding a 70-year-old man with paraneoplastic limbic encephalitis. He presented with a chief complaint of inability to recall any events. He had been well until one month before admission, and then he abruptly began to show progressive amnesia. At admission, the patient's score on the Revised Hasegawa Dementia Scale (HDS-R) showed a decline to 13/30, thus indicating the existence of severe disorientation and an impaired memory. The brain CT and EEG showed no specific abnormalities and an analysis of cerebrospinal fluid showed only a mild increase in the total protein level. A chest X-ray film revealed a mass in the right hilum, while a histological analysis of the biopsied specimen finally established a diagnosis of small cell lung carcinoma. The FDG-PET and the enhanced brain MRI showed a single small metastatic lesion in the cerebellum. After the 1st course of chemotherapy and whole brain radiation, cognitive function, especially the short-term memory, remarkably improved and the HDS-R score increased to 21/30. However, the tumor again increased in size during the 3(rd) and 4(th) courses of chemotherapy. Interestingly, cognitive function also worsened again and the score of HDS-R declined to 15/30, 20 weeks after the start of chemotherapy. Limbic encephalitis can be associated with malignant tumors, such as small cell lung carcinoma, and some reported cases have shown a cognitive improvement after tumor therapy. In our case, we also observed a reworsening of the cognitive function in association with the acquired chemoresistence. PMID:20339211

  12. Activation of delta-opioid receptors inhibits neuronal-like calcium channels and distal steps of Ca(2+)-dependent secretion in human small-cell lung carcinoma cells.

    PubMed

    Sher, E; Cesare, P; Codignola, A; Clementi, F; Tarroni, P; Pollo, A; Magnelli, V; Carbone, E

    1996-06-01

    Human small-cell lung carcinoma (SCLC) cells express neuronal-like voltage-operated calcium channels (VOCCs) and release mitogenic hormones such as serotonin (5-HT). Opioid peptides, on the other hand, have been shown to reduce SCLC cell proliferation by an effective autocrine pathway. Here we show that in GLC8 SCLC cells, only delta-opioid receptor subtype mRNA is expressed. Consistently, the selective delta-opioid agonist [D-Pen2-Pen5]-enkephalin (DPDPE), but not mu and kappa agonists, potently and dose-dependently inhibits high-threshold (HVA) VOCCs in these cells. As in peripheral neurons, this modulation is largely voltage-dependent, mediated by pertussis toxin (PTX)-sensitive G-proteins, cAMP-independent, and mainly affecting N-type VOCCs. With the same potency and selectivity, DPDPE also antagonizes the Ca(2+)-dependent release of [3H]serotonin ([3H]5-HT) from GLC8 cells. However, DPDPE inhibits not only the depolarization-induced release, but also the Ca(2+)-dependent secretion induced by thapsigargin or ionomycin. This suggests that besides inhibiting HVA VOCCs, opioids also exert a direct depressive action on the secretory apparatus in GLC8 cells. This latter effect also is mediated by a PTX-sensitive G-protein but, contrary to VOCC inhibition, it can be reversed by elevations of cAMP levels. These results show for the first time that opioids effectively depress both Ca2+ influx and Ca(2+)-dependent hormone release in SCLC cells by using multiple modulatory pathways. It can be speculated that the two mechanisms may contribute to the opioid antimitogenic action on lung neuroendocrine carcinoma cells. PMID:8642411

  13. Detachment of glycolytic enzymes from cytoskeleton of Lewis lung carcinoma and colon adenocarcinoma cells induced by clotrimazole and its correlation to cell viability and morphology.

    PubMed

    Penso, Julia; Beitner, Rivka

    2002-07-01

    Cancer cells are characterized by a high rate of glycolysis, which is their primary energy source. Glycolysis is known to be controlled by allosteric regulators, as well as by reversible binding of glycolytic enzymes to cytoskeleton. We report here that clotrimazole (l-(alpha-2-chlorotrityl)imidazole), the antifungal azole derivative, which was recently recognized as calmodulin antagonist, induced a dose-dependent detachment of the glycolytic enzymes, phosphofructokinase (ATP: D-fructose-6-phosphate 1-phosphotransferase, EC 2.7.1.11) and aldolase (D-fructose-l,6-bisphosphate D-glyceraldehyde-3-phosphate-lyase, EC 4.1.2.13), from cytoskeleton of LL/2 Lewis lung carcinoma cells and CT-26 colon adenocarcinoma cells. The detachment of glycolytic enzymes from cytoskeleton would reduce the provision of local ATP, in the vicinity of the cytoskeleton membrane, and would also affect cytoskeleton structure and cell shape. We show here that clotrimazole decreased the viability of LL/2 Lewis lung carcinoma cells and CT-26 colon adenocarcinoma cells. After 3h of incubation with clotrimazole, complete cell destruction was detected. Ultrastructural cell damage was manifested by disintegration of the outer membrane by scanning electron microscopy (SEM). The detachment of glycolytic enzymes from cytoskeleton, induced by clotrimazole, preceded the decrease in cell viability, which indicates that this is an early effect and not a result of cell death. Since the cytoskeleton is being recognized as an important modulator of cell function, proliferation, differentiation, and neoplasia, detachment of the glycolytic enzymes from cytoskeleton induced by clotrimazole, as well as its reported inhibitory action on cell proliferation, makes this drug the most promising agent in the treatment of cancer. PMID:12126931

  14. Prime-boost vaccination with SA-4-1BBL costimulatory molecule and survivin eradicates lung carcinoma in CD8+ T and NK cell dependent manner.

    PubMed

    Srivastava, Abhishek K; Sharma, Rajesh K; Yolcu, Esma S; Ulker, Vahap; MacLeod, Kathryn; Dinc, Gunes; Shirwan, Haval

    2012-01-01

    Subunit vaccines containing universal tumor associated antigens (TAAs) present an attractive treatment modality for cancer primarily due to their safety and potential to generate long-term immunological responses that can safeguard against recurrences. However, TAA-based subunit vaccines require potent adjuvants for therapeutic efficacy. Using a novel form of the 4-1BBL costimulatory molecule, SA-4-1BBL, as the adjuvant of choice, we previously demonstrated that a single vaccination with survivin (SVN) as a bona fide self TAA was effective in eradicating weakly immunogenic 3LL tumors in >70% of C57BL/6 mice. The present study was designed to i) assess the therapeutic efficacy of a prime-boost vaccination and ii) investigate the mechanistic basis of vaccine efficacy. Our data shows that a prime-boost vaccination strategy was effective in eradicating 3LL lung carcinoma in 100% of mice. The vaccine efficacy was correlated with increased percentages of CD8(+) T cells expressing IFN-γ as well as potent killing responses of both CD8(+) T and NK cells in the absence of detectable antibodies to ssDNA as a sign of autoimmunity. Antibody depletion of CD8(+) T cells one day before vaccination completely abrogated therapeutic efficacy, whereas depletion of CD4(+) T cells had no effect. Importantly, NK cell depletion had a moderate (∼50% reduction), but significant (p<0.05) effect on vaccine efficacy. Taken together, these results shed light on the mechanistic basis of the SA-4-1BBL/SVN subunit vaccine formulation in a lung carcinoma model and demonstrate the robust therapeutic efficacy of the prime-boost immunization strategy with important clinical implications. PMID:23144888

  15. MicroRNA-27b reverses docetaxel resistance of non-small cell lung carcinoma cells via targeting epithelial growth factor receptor.

    PubMed

    Chen, Shi; Wang, Qian; Zhou, Xian-Mei; Zhu, Ji-Ping; Li, Tian; Huang, Mao

    2016-07-01

    MicroRNA (miR)‑27b has been reported to partici-pate in regulating the activity of non‑small cell lung carcinoma (NSCLC) cells. Additionally, when downregulated in NSCLC it promotes resistance to docetaxel; however, the underlying molecular mechanism remains largely unknown. Using reverse transcription‑quantitative polymerase chain reaction, the present study determined that the expression of miR‑27b was significantly reduced in NSCLC cells that were resistant to docetaxel. In addition, epidermal growth factor receptor (EGFR) was identified as a possible target of miR‑27b by searching the online miRNA database, TargetScan. A luciferase assay further validated EGFR as an effective target gene of miR‑27b. In addition, it was determined that in tumor tissue samples resistant to docetaxel miR‑27b was significantly downregulated, whilst EGFR was significantly upregulated. miR‑27b negatively regulated the expression of EGFR. This was evident as the transfection of miR‑27b mimics led to downregulation of the expression levels of EGFR, whilst miR‑27b inhibitors upregulated the expression levels of EGFR. Furthermore, it was demonstrated that the transfection of miR‑27b mimics significantly suppressed the apoptosis and promote the viability of A549 human lung carcinoma cells. In line with this, the introduction of miR‑27b inhibitors significantly induced apoptosis and inhibited the proliferation of A549 cells. These results indicate that miR‑27b may promote NSCLC cell viability and enhance resistance to docetaxel treatment through direct inhibition of EGFR expression. Additionally, miR‑27b may become a promising molecular target for improving the effectiveness of chemotherapy with docetaxel. PMID:27221512

  16. Diagnosis and management of typical and atypical lung carcinoids.

    PubMed

    Pusceddu, Sara; Lo Russo, Giuseppe; Macerelli, Marianna; Proto, Claudia; Vitali, Milena; Signorelli, Diego; Ganzinelli, Monica; Scanagatta, Paolo; Duranti, Leonardo; Trama, Annalisa; Buzzoni, Roberto; Pelosi, Giuseppe; Pastorino, Ugo; de Braud, Filippo; Garassino, Marina Chiara

    2016-04-01

    An estimated 20% to 30% of all neuroendocrine tumours originate in the bronchial tree and lungs. According to the 2015 World Health Organization categorization, these tumours are separated into four subtypes characterized by increasing biological aggressiveness: typical carcinoid, atypical carcinoid, large-cell neuroendocrine carcinoma and small-cell carcinoma. Although typical and atypical lung carcinoids account for less than 1-5% of all pulmonary malignancies, the incidence of these neoplasms has risen significantly in recent decades. Surgery is the treatment of choice for loco-regional disease but for advanced lung carcinoids there is no recognized standard of care and successful management requires a multidisciplinary approach. The aim of this review is to provide a useful guide for the clinical management of lung carcinoids. PMID:26917456

  17. Papillary thyroid carcinoma with extensive squamous dedifferentiation metastatic to the lung: BRAF mutational analysis as a useful tool to rule out tumor to tumor metastasis.

    PubMed

    Acosta, Andres M; Pins, Michael R

    2016-02-01

    Tumors containing elements of both papillary thyroid carcinoma (PTC) and squamous cell carcinoma (SCC) are rare but well documented. When they present initially as metastatic disease in an organ that can harbor a primary SCC, the possibility of a tumor to tumor metastasis (TTM) must be considered. The aim of this case study is to illustrate how BRAF mutational analysis can be used to help differentiate between these two diagnoses. We report a 63-year-old male with a longstanding history of PTC metastatic to the brain and lymph nodes who presented to our institution with a right lower lobe lung mass after a 2-year recurrence-free interval. Histopathologic and immunohistochemical analysis revealed a composite neoplasm with distinct elements of both PTC and SCC. We performed BRAF (V600E) (c.1799 T > A) mutational analysis to help elucidate the origin of each component. This is the first time that BRAF sequencing has been used to discriminate between dedifferentiated PTC and TTM, to the best of our knowledge. In the context of metastatic PTC with SCC dedifferentiation, the presence of the identical BRAF (V600E) (c.1799 T > A) mutation in both components might help rule out tumor to tumor metastasis. PMID:26521063

  18. Effects of Feijining Decoction on vascular endothelial growth factor protein expression and changes of T cell subsets in Lewis lung carcinoma-bearing mice

    PubMed Central

    ZHOU, LIJIANG; PAN, YUZHEN; XING, YUQING; GAO, HONG; XIE, XIAODONG; YIN, DONGFENG

    2015-01-01

    Angiogenesis is crucial for cancer growth and metastasis. T cells are also key members of the adaptive immunity against tumorigenesis. The aim of the present study was to observe the effects of Feijining Decoction (FJND) on vascular endothelial growth factor (VEGF) protein expression and T cell subsets [cluster of differentiation 4+(CD4+) and CD8+ T lymphocyte] in Lewis lung carcinoma (LLC)-bearing mice. C57BL/6J mice were subcutaneously implanted with LLC cells. Forty carcinoma-bearing mice were randomly assigned to four groups (10 animals/group). The control group (CG) were the untreated group, the cisplatinum (DDP) group (DG) mice were treated with DDP, the FJND group (FG) were treated with FJND and the FJND + DDP group (FDG) were treated with FJND and DDP. Western blot and flow cytometry were used to evaluate the VEGF protein expression of tumor tissue and T cell subsets of the spleen. Spontaneous activity in 5 min was observed by the photoelectric counting method. DDP + FJND (FDG group) markedly inhibited tumor growth compared to the DG mice. The protein expression of VEGF was significantly downregulated in the carcinoma of FG mice compared to CG mice. VEGF protein expression was significantly reduced in FDG compared to DG mice. In the FG mice, the splenic CD4+ and CD4+/CD8+ cells were significantly increased compared to the CG mice, and the splenic CD4+ cells in the FDG mice were significantly increased compared to the DG group. In conclusion, FJND can inhibit tumor growth by downregulating VEGF protein expression and improving the immune function. PMID:26137245

  19. Cancer stem cells are underestimated by standard experimental methods in clear cell renal cell carcinoma.

    PubMed

    Gedye, Craig; Sirskyj, Danylo; Lobo, Nazleen C; Meens, Jalna; Hyatt, Elzbieta; Robinette, Michael; Fleshner, Neil; Hamilton, Robert J; Kulkarni, Girish; Zlotta, Alexandre; Evans, Andrew; Finelli, Antonio; Jewett, Michael A S; Ailles, Laurie E

    2016-01-01

    Rare cancer stem cells (CSC) are proposed to be responsible for tumour propagation and re-initiation and are functionally defined by identifying tumour-initiating cells (TICs) using the xenotransplantation limiting dilution assay (LDA). While TICs in clear cell renal cell carcinoma (ccRCC) appeared rare in NOD/SCID/IL2Rγ(-/-) (NSG) mice, xenografts formed more efficiently from small tumour fragments, indicating the LDA underestimated ccRCC TIC frequency. Mechanistic interrogation of the LDA identified multiple steps that influence ccRCC TIC quantitation. For example, tissue disaggregation destroys most ccRCC cells, common assays significantly overestimate tumour cell viability, and microenvironmental supplementation with human extracellular factors or pharmacological inhibition of anoikis increase clonogenicity and tumourigenicity of ccRCC cell lines and primary tumour cells. Identification of these previously uncharacterized concerns that cumulatively lead to substantial underestimation of TICs in ccRCC provides a framework for development of more accurate TIC assays in the future, both for this disease and for other cancers. PMID:27121191

  20. Cancer stem cells are underestimated by standard experimental methods in clear cell renal cell carcinoma

    PubMed Central

    Gedye, Craig; Sirskyj, Danylo; Lobo, Nazleen C.; Meens, Jalna; Hyatt, Elzbieta; Robinette, Michael; Fleshner, Neil; Hamilton, Robert J; Kulkarni, Girish; Zlotta, Alexandre; Evans, Andrew; Finelli, Antonio; Jewett, Michael A. S.; Ailles, Laurie E.

    2016-01-01

    Rare cancer stem cells (CSC) are proposed to be responsible for tumour propagation and re-initiation and are functionally defined by identifying tumour-initiating cells (TICs) using the xenotransplantation limiting dilution assay (LDA). While TICs in clear cell renal cell carcinoma (ccRCC) appeared rare in NOD/SCID/IL2Rγ−/− (NSG) mice, xenografts formed more efficiently from small tumour fragments, indicating the LDA underestimated ccRCC TIC frequency. Mechanistic interrogation of the LDA identified multiple steps that influence ccRCC TIC quantitation. For example, tissue disaggregation destroys most ccRCC cells, common assays significantly overestimate tumour cell viability, and microenvironmental supplementation with human extracellular factors or pharmacological inhibition of anoikis increase clonogenicity and tumourigenicity of ccRCC cell lines and primary tumour cells. Identification of these previously uncharacterized concerns that cumulatively lead to substantial underestimation of TICs in ccRCC provides a framework for development of more accurate TIC assays in the future, both for this disease and for other cancers. PMID:27121191

  1. Erlotinib Hydrochloride With or Without Carboplatin and Paclitaxel in Treating Patients With Stage III-IV Non-small Cell Lung Cancer

    ClinicalTrials.gov

    2016-06-29

    Adenosquamous Lung Carcinoma; Bronchioloalveolar Carcinoma; Lung Adenocarcinoma; Malignant Pericardial Effusion; Malignant Pleural Effusion; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Non-Small Cell Lung Cancer

  2. Prevention of growth of human lung carcinoma cells and induction of apoptosis by a novel phenoxazinone, 2-amino-4,4alpha-dihydro-4alpha,7-dimethyl-3H-phenoxazine-3-one.

    PubMed

    Abe, A; Yamane, M; Tomoda, A

    2001-04-01

    Anti-tumor effects of a novel phenoxazinone, 2-amino-4,4-dihydro-4alpha,7-dimethyl-3H-phenoxazine-3-one (Phx), which was synthesized by the reaction of 2-amino-5-methylphenol with bovine hemoglobin, were studied in terms of suppression of the proliferation of human lung carcinoma cells and apoptosis induction. When Phx was added to cultures of the human lung carcinoma cell lines A549 (adenocarcinoma) and H226 (squamous carcinoma), it caused the growth inhibition and the death of these cells. Phx also fragmented the DNA of these cells to oligonucleosomal-sized fragments, which is characteristic of the apoptosis, dependent on the dose and exposure time. The cellular death caused by the administration of Phx was partially reversed by the addition of Z-VAD-fmk, a caspase family inhibitor. Present results suggest that Phx demonstrates anti-cancer activity against human lung carcinoma cell lines A549 and H226, by inhibiting growth and inducing apoptosis. PMID:11335795

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

    NASA Astrophysics Data System (ADS)

    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.

  4. Morphological changes and nuclear translocation of DLC1 tumor suppressor protein precede apoptosis in human non-small cell lung carcinoma cells

    SciTech Connect

    Yuan Baozhu Jefferson, Amy M.; Millecchia, Lyndell; Popescu, Nicholas C.; Reynolds, Steven H.

    2007-11-01

    We have previously shown that reactivation of DLC1, a RhoGAP containing tumor suppressor gene, inhibits tumorigenicity of human non-small cell lung carcinoma cells (NSCLC). After transfection of NSCLC cells with wild type (WT) DLC1, changes in cell morphology were observed. To determine whether such changes have functional implications, we generated several DLC1 mutants and examined their effects on cell morphology, proliferation, migration and apoptosis in a DLC1 deficient NSCLC cell line. We show that WT DLC1 caused actin cytoskeleton-based morphological alterations manifested as cytoplasmic extensions and membrane blebbings in most cells. Subsequently, a fraction of cells exhibiting DLC1 protein nuclear translocation (PNT) underwent caspase 3-dependent apoptosis. We also show that the RhoGAP domain is essential for the occurrence of morphological alterations, PNT and apoptosis, and the inhibition of cell migration. DLC1 PNT is dependent on a bipartite nuclear localizing sequence and most likely is regulated by a serine-rich domain at N-terminal part of the DLC1 protein. Also, we found that DLC1 functions in the cytoplasm as an inhibitor of tumor cell proliferation and migration, but in the nucleus as an inducer of apoptosis. Our analyses provide evidence for a possible link between morphological alterations, PNT and proapoptotic and anti-oncogenic activities of DLC1 in lung cancer.

  5. Morphological changes and nuclear translocation of DLC1 tumor suppressor protein precede apoptosis in human non-small cell lung carcinoma cells.

    PubMed

    Yuan, Bao-Zhu; Jefferson, Amy M; Millecchia, Lyndell; Popescu, Nicholas C; Reynolds, Steven H

    2007-11-01

    We have previously shown that reactivation of DLC1, a RhoGAP containing tumor suppressor gene, inhibits tumorigenicity of human non-small cell lung carcinoma cells (NSCLC). After transfection of NSCLC cells with wild type (WT) DLC1, changes in cell morphology were observed. To determine whether such changes have functional implications, we generated several DLC1 mutants and examined their effects on cell morphology, proliferation, migration and apoptosis in a DLC1 deficient NSCLC cell line. We show that WT DLC1 caused actin cytoskeleton-based morphological alterations manifested as cytoplasmic extensions and membrane blebbings in most cells. Subsequently, a fraction of cells exhibiting DLC1 protein nuclear translocation (PNT) underwent caspase 3-dependent apoptosis. We also show that the RhoGAP domain is essential for the occurrence of morphological alterations, PNT and apoptosis, and the inhibition of cell migration. DLC1 PNT is dependent on a bipartite nuclear localizing sequence and most likely is regulated by a serine-rich domain at N-terminal part of the DLC1 protein. Also, we found that DLC1 functions in the cytoplasm as an inhibitor of tumor cell proliferation and migration, but in the nucleus as an inducer of apoptosis. Our analyses provide evidence for a possible link between morphological alterations, PNT and proapoptotic and anti-oncogenic activities of DLC1 in lung cancer. PMID:17888903

  6. The downregulation of Bcl-xL/Bcl-2-associated death promoter indicates worse outcomes in patients with small cell lung carcinoma

    PubMed Central

    Yu, Yaoyang; Zhong, Zhaokui; Guan, Yaowu

    2015-01-01

    It is well known that lung cancer is the 1st leading cause of death worldwide. Many reports have demonstrated that Bad, the Bcl-xL/Bcl-2-associated death promoter plays a crucial role in the intrinsic apoptosis pathway. The aim of this study was to explore the expression of Bad and its clinical significance in small cell lung carcinoma (SCLC) By analyzing the expression of Bad in 147 SCLC patient specimen, we found that Bad expression was remarkably decreased in 55.8% (82/147) cases, compared with the neighboring non-tumor tissues. Further study showed that Bad expression was correlated with adverse clinical characters such as clinical stage (P = 0.001), tumor size (P = 0.036) and tumor recurrence (P = 0.030). Furthermore, the results of Kaplan-Meier analysis showed that low Bad expression was significantly correlated to overall survival (P < 0.0001) and disease-free survival (P = 0.017) of patients with SCLC. Moreover, multivariate analyses revealed that Bad was an independent indicator of overall survival in SCLC (hazard ration = 0.620, 95% confidence interval: 0.389-0.987, P < 0.001). In summary, we can conclude that patients with SCLC represent downregulation of Bad and the latter could be served as a useful biomarker for the outcomes of SCLC. PMID:26722503

  7. Harmol induces apoptosis by caspase-8 activation independently of Fas/Fas ligand interaction in human lung carcinoma H596 cells.

    PubMed

    Abe, Akihisa; Yamada, Hiroyuki

    2009-06-01

    The beta-carboline alkaloids are naturally existing plant substances. It is known that these alkaloids have a wide spectrum of neuropharmacological, psychopharmacological, and antitumor effects. Therefore, they have been traditionally used in oriental medicine for the treatment of various diseases including cancers and malaria. In this study, harmol and harmalol, which are beta-carboline alkaloids, were examined for their antitumor effect on human lung carcinoma cell lines, and structure-activity relationship was also investigated. H596, H226, and A549 cells were treated with harmol and harmalol, respectively. Apoptosis was induced by harmol only in H596 cells. In contrast, harmalol had negligible cytotoxicity in three cell lines. Harmol induced caspase-3, caspase-8, and caspase-9 activities and caspase-3 activities accompanied by cleavage of poly-(ADP-ribose)-polymerase. Furthermore, harmol treatment decreased the native Bid protein, and induced the release of cytochrome c from mitochondria to cytosol. The apoptosis induced by harmol was completely inhibited by caspase-8 inhibitor and partially inhibited by caspase-9 inhibitor. The antagonistic antibody ZB4 blocked Fas ligand-induced apoptosis, but had no effect on harmol-induced apoptosis. Harmol had no significant effect on the expression of Fas. In conclusion, our results showed that the harmol could cause apoptosis-inducing effects in human lung H596 cells through caspase-8-dependent pathway but independent of Fas/Fas ligand interaction. PMID:19318910

  8. Treatment of Hepatocellular Carcinoma in the Community: Disparities in Standard Therapy

    PubMed Central

    Harlan, Linda C.; Parsons, Helen M.; Wiggins, Charles L.; Stevens, Jennifer L.; Patt, Yehuda Z.

    2015-01-01

    Background and Aims Hepatocellular carcinoma (HCC) incidence is expected to rise dramatically over the next decades because of increasing hepatitis C infections and obesity-related comorbidities. However, little information exists regarding the treatment of patients with HCC in the community setting. The purpose of this article was to characterize patterns of diagnosis, treatment, and survival for HCC in the community. Methods We identified 946 HCC patients in the 2007 National Cancer Institute's Patterns of Care study. Chi-square analyses and multivariable regression were used to examine patient and provider factors associated with treatment and survival by stage at diagnosis. Results Our primary findings indicate that liver transplants, embolization, or radiofrequency ablation for Barcelona Clinic Liver Cancer stage A patients were performed significantly less often for non-Hispanic blacks, Hispanics, patients in the highest income quartile, and patients with Medicaid. Patients with stage D disease were less likely to receive cancer therapy if they had Medicaid insurance compared to private insurance (p<0.001 for all). In multivariable analyses, all-cause mortality was associated with treatment in a hospital without a residency training program (hazard ratio [HR] 1.4 [1.1,1.9]), more advanced stage (HR: 10.6 [5.7, 19.5] stage D vs. A), and lack of appropriate treatment (HR: 2.4 [1.9,3.2]). Conclusions This is the first population-based study to evaluate therapy provided for HCC in the community. Current therapy depended on patients' HCC stage at diagnosis and other clinical and demographic factors. Overall, our study identifies those least likely to receive specific therapies in a variety of health care settings and can inform strategies for promoting appropriate therapy now and as new agents are developed. PMID:26020030

  9. Utility of a novel triple marker (combination of thyroid transcription factor 1, Napsin A, and P40) in the subclassification of non-small cell lung carcinomas using fine-needle aspiration cases.

    PubMed

    Sharma, Rajni; Wang, Yuting; Chen, Li; Gurda, Grzegorz T; Geddes, Susan; Gabrielson, Edward; Askin, Frederic; Li, Qing Kay

    2016-08-01

    Personalized treatment of lung cancer requires an accurate subclassification of non-small cell lung carcinoma (NSCLC) into adenocarcinoma (ADC), squamous cell carcinoma (SqCC), and other subtypes. In poorly differentiated tumors especially on small fine-needle aspirate specimens, the subclassification could be difficult in certain cases. Our previous study using resected tumor tissue has shown that the combination of commonly used individual markers (thyroid transcription factor 1 [TTF-1], P40, and Napsin A) into a novel triple marker has high sensitivity and specificity in subclassification of NSCLC and also the advantage of using minimal tumor tissue. In this study, we further evaluated the utility of this novel triple marker using fine-needle aspirate cases. We included primary NSCLC, consisting of 37 SqCCs (primary, 35; metastasis, 2) and 50 ADCs (primary, 29; metastasis, 21), 12 metastatic ADCs of nonpulmonary primary, and 10 small cell lung carcinomas. The immunohistochemical patterns were semiquantitatively scored. In lung SqCCs and ADCs, the sensitivity and specificity of the triple marker were 100% and 97.1% and 86.0% and 100%, respectively. The triple marker showed no immunoreactivity in 12 metastatic nonpulmonary ADCs. In 10 small cell lung carcinomas, TTF-1 had focal positivity in 40% of cases. The limitations of the triple marker include staining of alveolar macrophages (by TTF-1 and Napsin A), basal layer of bronchial epithelial cells (by P40), and nonspecific cytoplasmic staining of TTF-1. Our study not only supports our previous finding using resected tumor specimens but also provides evidence that the triple marker can be used for cytological material and preserving tumor tissue for molecular testing. PMID:27045515

  10. SLUG is required for SOX9 stabilization and functions to promote cancer stem cells and metastasis in human lung carcinoma.

    PubMed

    Luanpitpong, S; Li, J; Manke, A; Brundage, K; Ellis, E; McLaughlin, S L; Angsutararux, P; Chanthra, N; Voronkova, M; Chen, Y C; Wang, L; Chanvorachote, P; Pei, M; Issaragrisil, S; Rojanasakul, Y

    2016-06-01

    Cancer stem cells (CSCs) are a promising target for cancer therapy, particularly for metastatic lung cancers, but how CSCs are regulated is largely unknown. We identify two proteins, SLUG (encoded by SNAI2 gene) and SOX9, which are associated with advanced stage lung cancers and are implicated in the regulation of CSCs. Inhibition of either SLUG or SOX9 sufficiently inhibits CSCs in human lung cancer cells and attenuates experimental lung metastasis in a xenograft mouse model. Correlation between SLUG and SOX9 levels was observed remarkably, we therefore sought to explore their mechanistic relationship and regulation. SLUG, beyond its known function as an epithelial-mesenchymal transition transcription factor, was found to regulate SOX9 by controlling its stability via a post-translational modification process. SLUG interacts directly with SOX9 and prevents it from ubiquitin-mediated proteasomal degradation. SLUG expression and binding are necessary for SOX9 promotion of lung CSCs and metastasis in a mouse model. Together, our findings provide a novel mechanistic insight into the regulation of CSCs via SLUG-SOX9 regulatory axis, which represents a potential novel target for CSC therapy that may overcome cancer chemoresistance and relapse. PMID:26387547

  11. The cyclin-dependent kinase 2 inhibitor down-regulates interleukin-1beta-mediated induction of cyclooxygenase-2 expression in human lung carcinoma cells.

    PubMed

    Mukhopadhyay, Partha; Ali, M Aktar; Nandi, Animesh; Carreon, Peter; Choy, Hak; Saha, Debabrata

    2006-02-01

    Overexpression of cyclooxygenase-2 (COX-2) is frequently observed in several human cancers, including lung, colon, and head and neck. Malignancies are also associated with the dysregulation of cell cycle events and concomitant elevated activity of cyclin-dependent kinases (CDK). CDK2 is a key cell cycle regulatory protein that controls the transition of cells from G(1) to S phase. In this study, we furnish several lines of evidence that show a functional role for the CDK2 in interleukin-1beta (IL-1beta)-induced COX-2 expression in H358 human non-small cell lung carcinoma cell line by blocking CDK2 activity. First, we show that BMS-387032, a potent CDK2 inhibitor, blocks IL-1beta-induced expression as well as steady-state mRNA levels of COX-2. Second, we show that small interfering RNA that abrogates CDK2 expression also blocks IL-1beta-induced COX-2 expression. Third, results from in vitro kinase assays clearly show that IL-1beta induces CDK2 activity in H358 cells and this activity is significantly inhibited by BMS-387032. Moreover, CDK2 inhibition blocks IL-1beta-induced binding to the NF-IL6 element of the COX-2 promoter and inhibits transcription of the COX-2 gene. We also observed that BMS-387032 does not inhibit endogenous expression of COX-2 or prostaglandin synthesis in lung carcinoma cells. Finally, we provide evidence showing that IL-1beta-induced signaling events, such as p38 mitogen-activated protein kinase, phosphorylated stress-activated protein kinase/c-Jun NH(2)-terminal kinase, phosphorylated AKT, and phosphorylated extracellular signal-regulated kinase 1/2, are not inhibited by CDK2 inhibitor. Taken together, the data suggest that CDK2 activity may play an important event in the IL-1beta-induced COX-2 expression and prostaglandin E(2) synthesis and might represent a novel target for BMS-387032. PMID:16452236

  12. Oral administration of 3,3'-diindolylmethane inhibits lung metastasis of 4T1 murine mammary carcinoma cells in BALB/c mice.

    PubMed

    Kim, Eun Ji; Shin, Minjeong; Park, Heesook; Hong, Ji Eun; Shin, Hyun-Kyung; Kim, Jongdai; Kwon, Dae Young; Park, Jung Han Yoon

    2009-12-01

    3,3'-diindolylmethane (DIM) is the major in vivo product of the acid-catalyzed oligomerization of indole-3-carbinol present in cruciferous vegetables, and it has been shown to exhibit anticancer properties. In this study, we assessed the effects of DIM on the metastasis of 4T1 mouse mammary carcinoma cells. In vitro culture studies showed that DIM dose-dependently inhibited the migration, invasion, and adhesion of 4T1 cells at concentrations of 0-10 micromol/L without attendant changes in cell viability. In an in vivo lung metastasis model, 4T1 cells (2 x 10(5) cells/mouse) were injected into the tail veins of syngeneic female BALB/c mice. Beginning on the second day, the mice were subjected to gavage with 0-10 mg DIM/(kg body weight x d) for 13 d. Oral DIM administration resulted in a marked reduction in the number of pulmonary tumor nodules. DIM treatment significantly reduced the levels of matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1, and vascular cell adhesion molecule (VCAM)-1 and increased TIMP-2 levels in the sera and lungs of mice injected with 4T1 cells. Additionally, DIM treatment reduced the serum concentrations of interleukin (IL)-1beta, IL-6 and tumor necrosis factor (TNF)alpha. We have demonstrated that DIM profoundly inhibits the lung metastasis of 4T1 cells, which was accompanied by reduced levels of MMP, adhesion molecules, and proinflammatory cytokines. These results indicate that DIM has potential as an antimetastatic agent for the treatment of breast cancer. PMID:19864400

  13. The clinicopathological significance and ethnic difference of FHIT hypermethylation in non-small-cell lung carcinoma: a meta-analysis and literature review

    PubMed Central

    Wu, Xiaoyu; Wu, Guannan; Yao, Xuequan; Hou, Gang; Jiang, Feng

    2016-01-01

    Emerging evidence indicates that FHIT is a candidate tumor suppressor in many types of tumors including non-small-cell lung carcinoma (NSCLC). However, the prognostic value and correlation between FHIT hypermethylation and clinicopathological characteristics of NSCLC remains unclear. In this report, we performed a meta-analysis to evaluate the effects of FHIT hypermethylation on the incidence of NSCLC and clinicopathological characteristics of human NSCLC patients. Final analysis of 1,801 NSCLC patients from 18 eligible studies was performed. FHIT hypermethylation was found to be significantly higher in NSCLC than in normal lung tissue. The pooled odds ratio (OR) from ten studies included 819 NSCLC and 792 normal lung tissues (OR =7.51, 95% confidence interval [CI] =2.98–18.91, P<0.0001). Subgroup analysis based on ethnicity implied that FHIT hypermethylation level was higher in NSCLC tissues than in normal tissues in both Caucasians (P=0.02) and Asians (P<0.0001), indicating that the difference in Asians was much more significant. FHIT hypermethylation was also correlated with sex status, smoking status, as well as pathological types. In addition, patients with FHIT hypermethylation had a lower survival rate than those without (hazard ratio =1.73, 95% CI =1.10–2.71, P=0.02). The results of this meta-analysis suggest that FHIT hypermethylation is associated with an increased risk and poor survival in NSCLC patients. FHIT hypermethylation, which induces the inactivation of FHIT gene, plays an important role in the carcinogenesis and clinical outcome and may serve as a potential diagnostic marker and drug target of NSCLC. PMID:26929601

  14. Association of Nuclear PIM1 Expression with Lymph Node Metastasis and Poor Prognosis in Patients with Lung Adenocarcinoma and Squamous Cell Carcinoma

    PubMed Central

    Jiang, Richeng; Wang, Xinyue; Jin, Ziliang; Li, Kai

    2016-01-01

    Increasing evidence indicates that aberrant expression of PIM1, p-STAT3 and c-MYC is involved in the pathogenesis of various solid tumors, but its prognostic value is still unclear in non-small cell lung cancer (NSCLC). Here, we sought to evaluate the expression and prognostic role of these markers in patients with lung adenocarcinoma (AD) and squamous cell carcinoma (SCC). Real time RT-PCR and Western blotting was used to analyze the mRNA and protein expression of PIM1 in NSCLC cell lines, respectively. The expression of PIM1, p-STAT3, and c-MYC was immunohistochemically tested in archival tumor samples from 194 lung AD and SCC patients. High nuclear PIM1 expression was detected in 43.3% of ADs and SCCs, and was significantly correlated with lymph node (LN) metastasis (P = 0.028) and histology (P = 0.003). High nuclear PIM1 expression (P = 0.034), locally advanced stage (P < 0.001), AD (P = 0.007) and poor pathologic differentiation (P = 0.002) were correlated with worse disease-free survival (DFS). High nuclear PIM1 expression (P = 0.009), advanced clinical stage (P < 0.001) and poor pathologic differentiation (P = 0.004) were independent unfavorable prognostic factors for overall survival (OS). High p-STAT3 expression was not associated with OS but significantly correlated with LN metastasis, while c-MYC was not significantly correlated with any clinicopathological parameter or survival. Therefore, in AD and SCC patients, nuclear PIM1 expression level is an independent factor for DFS and OS and it might serve as a predictive biomarker for outcome. PMID:26918046

  15. Leptospermum flavescens Constituent-LF1 Causes Cell Death through the Induction of Cell Cycle Arrest and Apoptosis in Human Lung Carcinoma Cells

    PubMed Central

    Navanesan, Suerialoasan; Abdul Wahab, Norhanom; Manickam, Sugumaran; Sim, Kae Shin

    2015-01-01

    Leptospermum flavescens Sm. (Myrtaceae), locally known as ‘Senna makki’ is a smallish tree that is widespread and recorded to naturally occur in the montane regions above 900 m a.s.l from Burma to Australia. Although the species is recorded to be used traditionally to treat various ailments, there is limited data on biological and chemical investigations of L. flavescens. The aim of the present study was to investigate and understand the ability of L. flavescens in inducing cell death in lung cancer cells. The cytotoxic potentials of the extraction yields (methanol, hexane, ethyl acetate and water extracts as wells as a semi pure fraction, LF1) were evaluated against two human non-small cell lung carcinoma cell lines (A549 and NCI-H1299) using the MTT assay. LF1 showed the greatest cytotoxic effect against both cell lines with IC50 values of 7.12 ± 0.07 and 9.62 ± 0.50 μg/ml respectively. LF1 treated cells showed a sub-G1 region in the cell cycle analysis and also caused the presence of apoptotic morphologies in cells stained with acridine orange and ethidium bromide. Treatment with LF1 manifested an apoptotic population in cells that were evaluated using the Annexin V/ propidium iodide assay. Increasing dosage of LF1 caused a rise in the presence of activated caspase-3 enzymes in treated cells. Blockage of cell cycle progression was also observed in LF1-treated cells. These findings suggest that LF1 induces apoptosis and cell cycle arrest in treated lung cancer cells. Further studies are being conducted to isolate and identify the active compound as well to better understand the mechanism involved in inducing cell death. PMID:26287817

  16. In vitro activities of 3-hydroxy-1,5,6-trimethoxy-2-methyl-9,10-anthraquinone against non-small cell lung carcinoma.

    PubMed

    Feng, Shi-Xiu; Guan, Qiunong; Chen, Tao; Du, Caigan

    2012-07-01

    Medicinal herbs are the preferred candidates for drug discovery against human diseases including cancer. The roots of Prismatomeris connata have been used in traditional herbal medicine to treat many health problems, particularly pneumoconiosis. This study was to test the anti-tumor activity of 3-hydroxy-1,5,6-trimethoxy-2-methyl-9,10-anthraquinone (PCON6), a major anthraquinone derivative from C. connata, against lung cancer. Cell viability in cultures was assessed by MTT assay. Cell death or apoptosis was determined with annexin-V and 7-aminoactinomycin D staining. Cell cycle was analyzed by both propidium iodide DNA staining and BrdU incorporation assay. Here we showed that in a panel of fifteen different tumor cells lines, a group of four non-small cell lung carcinoma (NSCLC) cell lines exhibited a relatively higher sensitivity to PCON6 growth inhibition than the rest of most non-lung cancer cell lines (p = 0.0461). Further studies demonstrated that the suppression of NSCLC H520 cell growth by PCON6 was associated with its induction of apoptosis at 20 μM (p = 0.0008), and of cell accumulation at S phase cell cycle (p < 0.05) that was further supported by a decrease in cdc2 protein expression. This preliminary study suggests that natural compound PCON6 has relatively selective cytotoxicity against NSCLC growth and represent a concept of developing a novel drug therapy specific for NSCLC based on the roots of C. connata or PCON6. PMID:22864748

  17. Correlation of dosimetric parameters obtained with the analytical anisotropic algorithm and toxicity of chest chemoradiation in lung carcinoma

    SciTech Connect

    Cartier, Lysian; Auberdiac, Pierre; Khodri, Mustapha; Malkoun, Nadia; Chargari, Cyrus; Thorin, Julie; Melis, Adrien; Talabard, Jean-Noeel; Laroche, Guy de; Fournel, Pierre; Tiffet, Olivier; Schmitt, Thierry; and others

    2012-07-01

    The purpose of this study was to analyze and revisit toxicity related to chest chemoradiotherapy and to correlate these side effects with dosimetric parameters obtained using analytical anisotropic algorithm (AAA) in locally unresectable advanced lung cancer. We retrospectively analyzed data from 47 lung cancer patients between 2005 and 2008. All received conformal 3D radiotherapy using high-energy linear accelerator plus concomitant chemotherapy. All treatment planning data were transferred into Eclipse 8.05 (Varian Medical Systems, Palo Alto, CA) and dosimetric calculations were performed using AAA. Thirty-three patients (70.2%) developed acute pneumopathy after radiotherapy (grades 1 and 2). One patient (2.1%) presented with grade 3 pneumopathy. Thirty-one (66%) presented with grades 1-2 lung fibrosis, and 1 patient presented with grade 3 lung fibrosis. Thirty-four patients (72.3%) developed grade 1-2 acute oesophagic toxicity. Four patients (8.5%) presented with grades 3 and 4 dysphagia, necessitating prolonged parenteral nutrition. Median prescribed dose was 64 Gy (range 50-74) with conventional fractionation (2 Gy per fraction). Dose-volume constraints were respected with a median V20 of 23.5% (maximum 34%) and a median V30 of 17% (maximum 25%). The median dose delivered to healthy contralateral lung was 13.1 Gy (maximum 18.1 Gy). At univariate analysis, larger planning target volume and V20 were significantly associated with the probability of grade {>=}2 radiation-induced pneumopathy (p = 0.022 and p = 0.017, respectively). No relation between oesophagic toxicity and clinical/dosimetric parameters could be established. Using AAA, the present results confirm the predictive value of the V20 for lung toxicity as already demonstrated with the conventional pencil beam convolution approach.

  18. Drug-induced myocarditis after nivolumab treatment in a patient with PDL1- negative squamous cell carcinoma of the lung.

    PubMed

    Semper, H; Muehlberg, F; Schulz-Menger, J; Allewelt, M; Grohé, C

    2016-09-01

    Immunotherapy such as nivolumab is a new promising therapeutic option for advanced stage non small cell lung cancer (NSCLC). Due to the interference with the immune system previously unknown side effects are observed both in clinical studies and experience. Autoimmune phenomena effecting skin, gastrointestinal tract, endocrine glands, kidney and lung have been described. Up to now there is only limited information regarding potential cardiac side effects. We present a case of symptomatic drug induced myocarditis after nine cycles of nivolumab in a patient with efficient anticancer response. PMID:27565924

  19. PET-Adjusted Intensity Modulated Radiation Therapy and Combination Chemotherapy in Treating Patients With Stage II-IV Non-small Cell Lung Cancer

    ClinicalTrials.gov

    2016-01-10

    Metastatic Malignant Neoplasm in the Brain; Recurrent Non-Small Cell Lung Carcinoma; Stage IIA Non-Small Cell Lung Carcinoma; Stage IIB Non-Small Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Non-Small Cell Lung Cancer

  20. High-Dose-Rate Brachytherapy for Non-Small-Cell Lung Carcinoma: A Retrospective Study of 226 Patients

    SciTech Connect

    Aumont-le Guilcher, Maud; Prevost, Bernard; Sunyach, Marie Pierre; Peiffert, Didier; Maingon, Philippe; Thomas, Laurence; Williaume, Daniele; Begue, Mickael; Lerouge, Delphine; Campion, Loic; Mahe, Marc-Andre

    2011-03-15

    Purpose: To evaluate the efficacy and toxicity of high-dose-rate (HDR) brachytherapy in patients with inoperable endobronchial carcinoma. Methods and Materials: We retrospectively reviewed the records (April 1991-May 2004) of patients with non-small-cell carcinoma, with no extrabronchial spread on computed tomography scans, who underwent HDR brachytherapy because of contraindications to surgery and external beam radiation therapy. Kaplan-Meier survival curves were compared by the log-rank test. Prognostic factors were analyzed by multivariate analysis. Results: 226 patients (223 men, 3 women, mean age: 62.2 years (range, 40-84)) were included. Of those, 217 (97%) had squamous cell carcinoma (Tis/T1/T2/Tx: 60/153/9/4). Dose was prescribed at 1 cm from the radius (24-35 Gy in 4-6 fractions). Mean follow-up was 30.4 months (range, 9-116). Complete endoscopic response rate was 93.6% at 3 months. One hundred twenty-eight patients (56%) died of intercurrent disease (n = 45), local failure (n = 36), metastasis (n = 10), local failure and metastasis (n = 11), complications (n = 13), and other causes (n = 12). The 2-year and 5-year survival rates were, respectively, 57% and 29% (overall) (median, 28.6 months), 81% and 56% (cancer-specific), and 68% and 50% (local disease-free). Acute toxicity included pneumothorax (1.5%) and mucosal inflammation (10%). Late complications were hemoptysis (6.6% with 5% of fatalities), bronchitis (19.5%), and necrosis (3.5%). In multivariate analysis, a distal tumor location and the use of two catheters were associated with improved local disease-free survival (p = 0.003 and p = 0.007, respectively) and a distal tumor location with improved overall survival (p = 0.0001). Conclusions: This large retrospective study confirms that HDR brachytherapy is an efficient and safe treatment in patients with inoperable endobronchial carcinoma.

  1. Antioxidant Activity and Cytotoxicity Effect of Cocoa Beans Subjected to Different Processing Conditions in Human Lung Carcinoma Cells

    PubMed Central

    Bauer, Deborah; de Abreu, Joel Pimentel; Oliveira, Hilana Salete Silva; Goes-Neto, Aristoteles; Koblitz, Maria Gabriela Bello

    2016-01-01

    Lung cancer is a common malignancy in men and the second leading cause of cancer-related mortality in men in the western world. Phenolic cocoa ingredients have a strong antioxidative activity and the potential to have a protective effect against cancer. In the present study, we have evaluated the influence of cocoa beans subjected to different processing conditions on cell viability and apoptosis of human lung cancer cells (A549). We measured the viability of lung cells treated with cocoa beans, unroasted slates (US), roasted slates (RS), unroasted well fermented (UWF) cocoa, and roasted well fermented (RWF) cocoa for 24 h. Using an MTT assay, we observed a decrease in the viability of A549 cells after treatment with cocoa bean extracts. Flow cytometer analysis revealed that cocoa beans increased the percentage of cells in sub-G1 phase and promoted up to twofold increase of apoptotic cells when compared to the control group. Taken together, the present study suggests that cocoa beans may have a protective effect against lung cancer. PMID:27034742

  2. Antioxidant Activity and Cytotoxicity Effect of Cocoa Beans Subjected to Different Processing Conditions in Human Lung Carcinoma Cells.

    PubMed

    Bauer, Deborah; de Abreu, Joel Pimentel; Oliveira, Hilana Salete Silva; Goes-Neto, Aristoteles; Koblitz, Maria Gabriela Bello; Teodoro, Anderson Junger

    2016-01-01

    Lung cancer is a common malignancy in men and the second leading cause of cancer-related mortality in men in the western world. Phenolic cocoa ingredients have a strong antioxidative activity and the potential to have a protective effect against cancer. In the present study, we have evaluated the influence of cocoa beans subjected to different processing conditions on cell viability and apoptosis of human lung cancer cells (A549). We measured the viability of lung cells treated with cocoa beans, unroasted slates (US), roasted slates (RS), unroasted well fermented (UWF) cocoa, and roasted well fermented (RWF) cocoa for 24 h. Using an MTT assay, we observed a decrease in the viability of A549 cells after treatment with cocoa bean extracts. Flow cytometer analysis revealed that cocoa beans increased the percentage of cells in sub-G1 phase and promoted up to twofold increase of apoptotic cells when compared to the control group. Taken together, the present study suggests that cocoa beans may have a protective effect against lung cancer. PMID:27034742

  3. C-Arm Cone-Beam CT-Guided Transthoracic Lung Core Needle Biopsy as a Standard Diagnostic Tool

    PubMed Central

    Jaconi, Marta; Pagni, Fabio; Vacirca, Francesco; Leni, Davide; Corso, Rocco; Cortinovis, Diego; Bidoli, Paolo; Bono, Francesca; Cuttin, Maria S.; Valente, Maria G.; Pesci, Alberto; Bedini, Vittorio A.; Leone, Biagio E.

    2015-01-01

    Abstract C-arm cone-beam computed tomography (CT)-guided transthoracic lung core needle biopsy (CNB) is a safe and accurate procedure for the evaluation of patients with pulmonary nodules. This article will focus on the clinical features related to CNB in terms of diagnostic performance and complication rate. Moreover, the concept of categorizing pathological diagnosis into 4 categories, which could be used for clinical management, follow-up, and quality assurance is also introduced. We retrospectively collected data regarding 375 C-arm cone-beam CT-guided CNBs from January 2010 and June 2014. Clinical and radiological variables were evaluated in terms of success or failure rate. Pathological reports were inserted in 4 homogenous groups (nondiagnostic-L1, benign-L2, malignant not otherwise specified-L3, and malignant with specific histotype-L4), defining for each category a hierarchy of suggested actions. The sensitivity, specificity, and positive and negative predictive value and accuracy for patients subjected to CNBs were of 96.8%, 100%, 100%, 100%, and 97.2%, respectively. Roughly 75% of our samples were diagnosed as malignant, with 60% lung adenocarcinoma diagnoses. Molecular analyses were performed on 85 malignant samples to verify applicability of targeted therapy. The rate of “nondiagnostic” samples was 12%. C-arm cone-beam CT-guided transthoracic lung CNB can represent the gold standard for the diagnostic evaluation of pulmonary nodules. A clinical and pathological multidisciplinary evaluation of CNBs was needed in terms of integration of radiological, histological, and oncological data. This approach provided exceptional performances in terms of specificity, positive and negative predictive values; sensitivity in our series was lower compared with other large studies, probably due to the application of strong criteria of adequacy for CNBs (L1 class rate). The satisfactory rate of collected material was evaluated not only in terms of merely diagnostic

  4. Lung cancer - non-small cell

    MedlinePlus

    Cancer - lung - non-small cell; Non-small cell lung cancer; NSCLC; Adenocarcinoma - lung; Squamous cell carcinoma - lung ... Smoking causes most cases (around 90%) of lung cancer. The risk ... day and for how long you have smoked. Being around the smoke ...

  5. Targeted therapy for non-small cell lung cancer: current standards and the promise of the future

    PubMed Central

    Chan, Bryan A.

    2015-01-01

    In recent years, there has been a major paradigm shift in the management of non-small cell lung cancer (NSCLC). NSCLC should now be further sub-classified by histology and driver mutation if one is known or present. Translational research advances now allow such mutations to be inhibited by either receptor monoclonal antibodies (mAb) or small molecule tyrosine kinase inhibitors (TKI). Whilst empirical chemotherapy with a platinum-doublet remains the gold standard for advanced NSCLC without a known driver mutation, targeted therapy is pushing the boundary to significantly improve patient outcomes and quality of life. In this review, we will examine the major subtypes of oncogenic drivers behind NSCLC as well as the development of targeted agents available to treat them both now and in the foreseeable future. PMID:25806345

  6. International Society for Heart and Lung Transplantation working formulation of a standardized nomenclature for cardiac allograft vasculopathy-2010.

    PubMed

    Mehra, Mandeep R; Crespo-Leiro, Maria G; Dipchand, Anne; Ensminger, Stephan M; Hiemann, Nicola E; Kobashigawa, Jon A; Madsen, Joren; Parameshwar, Jayan; Starling, Randall C; Uber, Patricia A

    2010-07-01

    The development of cardiac allograft vasculopathy remains the Achilles heel of cardiac transplantation. Unfortunately, the definitions of cardiac allograft vasculopathy are diverse, and there are no uniform international standards for the nomenclature of this entity. This consensus document, commissioned by the International Society of Heart and Lung Transplantation Board, is based on best evidence and clinical consensus derived from critical analysis of available information pertaining to angiography, intravascular ultrasound imaging, microvascular function, cardiac allograft histology, circulating immune markers, non-invasive imaging tests, and gene-based and protein-based biomarkers. This document represents a working formulation for an international nomenclature of cardiac allograft vasculopathy, similar to the development of the system for adjudication of cardiac allograft rejection by histology. PMID:20620917

  7. Targeted therapy for squamous cell lung cancer

    PubMed Central

    Liao, Rachel G.; Watanabe, Hideo; Meyerson, Matthew; Hammerman, Peter S.

    2013-01-01

    SUMMARY Lung squamous cell carcinoma (SqCC) is the second most common subtype of non-small-cell lung cancer and leads to 40,000–50,000 deaths per year in the USA. Management of non-small-cell lung cancer has dramatically changed over the past decade with the introduction of targeted therapeutic agents for genotypically selected individuals with lung adenocarcinoma. These agents lead to improved outcomes, and it has now become the standard of care to perform routine molecular genotyping of lung adenocarcinomas. By contrast, progress in lung SqCC has been modest, and there has yet to be a successful demonstration of targeted therapy in this disease. Here, we review exciting work from ongoing genomic characterization and biomarker validation efforts that have nominated several likely therapeutic targets in lung SqCCs. These studies suggest that targeted therapies are likely to be successful in the treatment of lung SqCCs and should be further explored in both preclinical models and in clinical trials. PMID:23956794

  8. Cell Membrane CD44v6 Levels in Squamous Cell Carcinoma of the Lung: Association with High Cellular Proliferation and High Concentrations of EGFR and CD44v5

    PubMed Central

    Ruibal, Álvaro; Aguiar, Pablo; Del Río, María Carmen; Nuñez, Matilde Isabel; Pubul, Virginia; Herranz, Michel

    2015-01-01

    Membranous CD44v6 levels in tumors and surrounding samples obtained from 94 patients with squamous cell lung carcinomas were studied and compared to clinical stage, cellular proliferation, membranous CD44v5 levels, epidermal growth factor receptor EGFR and cytoplasmatic concentrations of CYFRA 21.1. CD44v6 positive values were observed in 33/38 non-tumor samples and in 76/94 tumor samples, but there were not statistically significant differences between both subgroups. In CD44v6 positive tumor samples, CD44v6 was not associated with clinical stage, histological grade, ploidy and lymph node involvement, but significant association was found with high cellular proliferation. Likewise, CD44v6 positive tumors had significantly higher levels of EGFR and CD44v5. In patients with squamous cell lung carcinomas and clinical stage I, positive CD44v6 cases were associated with the same parameters. Furthermore, positive CD44v5 squamous tumors were associated significantly with histological grade III and lower levels of CYFRA21.1. Our findings support the value of CD44v6 as a possible indicator of poor outcome in patients with squamous lung carcinomas. PMID:25809603

  9. Cell membrane CD44v6 levels in squamous cell carcinoma of the lung: association with high cellular proliferation and high concentrations of EGFR and CD44v5.

    PubMed

    Ruibal, Álvaro; Aguiar, Pablo; Del Río, María Carmen; Nuñez, Matilde Isabel; Pubul, Virginia; Herranz, Michel

    2015-01-01

    Membranous CD44v6 levels in tumors and surrounding samples obtained from 94 patients with squamous cell lung carcinomas were studied and compared to clinical stage, cellular proliferation, membranous CD44v5 levels, epidermal growth factor receptor EGFR and cytoplasmatic concentrations of CYFRA 21.1. CD44v6 positive values were observed in 33/38 non-tumor samples and in 76/94 tumor samples, but there were not statistically significant differences between both subgroups. In CD44v6 positive tumor samples, CD44v6 was not associated with clinical stage, histological grade, ploidy and lymph node involvement, but significant association was found with high cellular proliferation. Likewise, CD44v6 positive tumors had significantly higher levels of EGFR and CD44v5. In patients with squamous cell lung carcinomas and clinical stage I, positive CD44v6 cases were associated with the same parameters. Furthermore, positive CD44v5 squamous tumors were associated significantly with histological grade III and lower levels of CYFRA21.1. Our findings support the value of CD44v6 as a possible indicator of poor outcome in patients with squamous lung carcinomas. PMID:25809603

  10. Prospective randomized study of various irradiation doses and fractionation schedules in the treatment of inoperable non-oat-cell carcinoma of the lung

    SciTech Connect

    Perez, C.A.; Stanley, K.; Rubin, P.; Kramer, S.; Brady, L.; Perez-Tamayo, R.; Brown, G.S.; Concannon, J.; Rotman, M.; Seydel, H.G.

    1980-06-01

    Analysis is presented of a prospective randomized study involving 365 patients with histologically proven unresectable non-oat-cell carcinoma of the lung treated with deffinitive radiotherapy. The patients were radomized to one of four treatment regimens: 4000 rad split course, or 4000, 5000, or 6000-rad continuous courses in five fractions per week. Ninety to 100 patients were accessioned to each group. The one-year survival rate is 50% and the two-year survival rate, 25%. The patients treated with the split course have the lowest survival rate in comparison with the other groups. The complete and partial local regression of tumor was 49% in patients treated with 4000 rad and 55% in the groups treated with 5000 and 6000 rad. For patients who achieved complete regression of the tumor following irradiation, the two-year survival rate is 40%, in contrast to 20% for those with partial regression, and no survivors among the patients with stable or progressive disease. The incidence of intrathoracic recurrence was 33% for patients treated with 6000 rad, 39% for those receiving 5000 rad, and 44 to 49% for those treated with a 4000-rad split or continuous course. At present, the data stongly suggest that patients treated with 5000 or 6000 rad have a better response, tumor control, and survival rate than those receiving lower doses. Patients with high performance status or with tumors in earlier stages have a two-year survival rate of approx. 40%, in comparison with 20% for other patients. The various irradiation regimens have been well tolerated, with complications being slightly higher in the 4000-rad split course group and in the 6000-rad continuous course group. The most frequent complications have been pneumonitis, pulmonary fibrosis, and dyspagia due to transient esophagitis. Further investigation will be necessary before the optimal management of patients with bronchogenic carcinoma by irradiation is established.

  11. A critical re-assessment of DNA repair gene promoter methylation in non-small cell lung carcinoma

    PubMed Central

    Do, Hongdo; Wong, Nicholas C.; Murone, Carmel; John, Thomas; Solomon, Benjamin; Mitchell, Paul L.; Dobrovic, Alexander

    2014-01-01

    DNA repair genes that have been inactivated by promoter methylation offer potential therapeutic targets either by targeting the specific repair deficiency, or by synthetic lethal approaches. This study evaluated promoter methylation status for eight selected DNA repair genes (ATM, BRCA1, ERCC1, MGMT, MLH1, NEIL1, RAD23B and XPC) in 56 non-small cell lung cancer (NSCLC) tumours and 11 lung cell lines using the methylation-sensitive high resolution melting (MS-HRM) methodology. Frequent methylation in NEIL1 (42%) and infrequent methylation in ERCC1 (2%) and RAD23B (2%) are reported for the first time in NSCLC. MGMT methylation was detected in 13% of the NSCLCs. Contrary to previous studies, methylation was not detected in ATM, BRCA1, MLH1 and XPC. Data from The Cancer Genome Atlas (TCGA) was consistent with these findings. The study emphasises the importance of using appropriate methodology for accurate assessment of promoter methylation. PMID:24569633

  12. Genomic profile, smoking, and response to anti-PD-1 therapy in non-small cell lung carcinoma

    PubMed Central

    Hellmann, Matthew; Rizvi, Naiyer; Wolchok, Jedd D.; Chan, Timothy A.

    2016-01-01

    ABSTRACT The recent successes of immune checkpoint therapies have established a new era for the treatment of patients with cancer, yet the predictors of response remain largely undetermined. We recently demonstrated that the genomic landscape of lung cancers substantially influences the response to programmed cell death 1 receptor (PD-1) blockade, providing new insights into the molecular determinants of the response to immunotherapy. PMID:27308563

  13. 18F-FDG PET/CT of advanced gastric carcinoma and association of HER2 expression with standardized uptake value

    PubMed Central

    Kim, Jin Suk; Young Park, Shin

    2014-01-01

    Objective(s): Expression of HER2 in gastric carcinoma has direct prognostic and therapeutic implications in patient management. The aim of this study is to determine whether a relationship exists between standardized uptake value (SUV) and expression of HER2 in advanced gastric carcinoma. Methods: We analyzed the 18F-FDG PET/CT results of 109 patients that underwent gastrectomy for advanced gastric carcinoma. The 18F-FDG PET/CT imaging was requested at the initial staging before surgery. The examinations were evaluated semi-quantitatively, with calculation of maximum standardized uptake values (SUVmax). The clinicopathologic factors, including HER2 overexpression, were determined from tissue obtained from the primary tumor. Metabolic and clincopathologic parameters were correlated using a t-test, one way ANOVA and chi-square test. Results: Immunohistochemically, 26 patients (23.8%) showed HER2 overexpression. This overexpression was significantly associated with high SUV level (P=0.02). The SUV level was significantly correlated with tumor size (P=0.02) and differentiation (P<0.001), and Lauren histologic type (P=0.04). Multivariate analysis showed HER2 overexpression, large tumor size, and differentiation (P=0.022, P=0.002, P<0.001) were significantly correlated with the high level of SUV in advanced gastric carcinoma. No association was found between SUV and T stage and lymph node metastasis. A receiver-operating characteristic curve demonstrated a SUVmax of 3.5 to be the optimal cutoff for predicting HER2 overexpression (sensitivity; 76.9%, specificity; 60.2%). Conclusion: An association exists between high SUV and HER2 overexpression and 18F-FDG PET/CT could be a useful tool to predict the biological characteristics of gastric carcinoma.

  14. 78 FR 35575 - Black Lung Benefits Act: Standards for Chest Radiographs

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-13

    ... 1980. See 45 FR 13678, 13680-81 (February 29, 1980). Codified at 20 CFR 718.102, 718.202, and Appendix... standards on NIOSH's then-current regulations, which HHS had published on August 1, 1978. 43 FR 33713... generally 45 FR 13680-81 (February 29, 1980). Although NIOSH later revised two of the 42 CFR part...

  15. 78 FR 35549 - Black Lung Benefits Act: Standards for Chest Radiographs

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-13

    ... X-rays in 1980. See 45 FR 13678, 13680-81 (February 29, 1980). Codified at 20 CFR 718.102, 718.202... standards on NIOSH's then-current regulations, which HHS had published on August 1, 1978. 43 FR 33713... generally 45 FR 13680-81 (February 29, 1980). Although NIOSH later revised two of the 42 CFR part...

  16. Enhanced efficacy of combination therapy with adeno-associated virus-delivered pigment epithelium-derived factor and cisplatin in a mouse model of Lewis lung carcinoma

    PubMed Central

    HE, SHA-SHA; WU, QIN-JIE; GONG, CHANG YANG; LUO, SHUN-TAO; ZHANG, SHUANG; LI, MENG; LU, LIAN; WEI, YU-QUAN; YANG, LI

    2014-01-01

    Pigment epithelium-derived factor (PEDF) is a potent inhibitor of angiogenesis, and the antitumor effect of adeno-associated virus (AAV)-mediated PEDF expression has been demonstrated in a range of animal models. The combined treatment of low-dose chemotherapy and gene therapy inhibits the growth of solid tumors more effectively than current traditional therapies or gene therapy alone. In the present study, the effect of treatment with an AAV2 vector harboring the human PEDF (hPEDF) gene in combination with low-dose cisplatin on the growth of Lewis lung carcinoma (LLC) in mice was assessed. LLC cells were infected with AAV-enhanced green fluorescent protein (EGFP) in the presence or absence of cisplatin, and then the effect of cisplatin on AAV-mediated gene expression was evaluated by image and flow cytometric analysis. Tumor growth, survival time, vascular endothelial growth factor (VEGF) expression, microvessel density (MVD) and apoptotic index were analyzed in C57BL/6 mice treated with AAV-hPEDF, cisplatin or cisplatin plus AAV-hPEDF. The results of the present study provide evidence that cisplatin treatment is able to enhance AAV-mediated gene expression in LLC cells. In addition, the combined treatment of cisplatin plus AAV-hPEDF markedly prolonged the survival time of the mice and inhibited tumor growth, resulting in significant suppression of tumor angiogenesis and induction of tumor apoptosis in vivo, and also protected against cisplatin-related toxicity. These findings suggest that combination of AAV-hPEDF and cisplatin has potential as a novel therapeutic strategy for lung cancer. PMID:24714917

  17. Regulatory Role of KEAP1 and NRF2 in PPARγ Expression and Chemoresistance in Human Non-small Cell Lung Carcinoma Cells

    PubMed Central

    Zhan, Lijuan; Zhang, Hao; Zhang, Qiang; Woods, Courtney G.; Chen, Yanyan; Xue, Peng; Dong, Jian; Tokar, Erik J.; Xu, Yuanyuan; Hou, Yongyong; Fu, Jingqi; Yarborough, Kathy; Wang, Aiping; Qu, Weidong; Waalkes, Michael P.; Andersen, Melvin E.; Pi, Jingbo

    2012-01-01

    The nuclear factor-E2-related factor 2 (NRF2) serves as a master regulator in cellular defense against oxidative stress and chemical detoxification. However, persistent activation of NRF2 resulting from mutations of NRF2 and/or downregulation or mutations of its suppressor Kelch-like ECH-associated protein 1 (KEAP1) are associated with tumorigenicity and chemoresistance of non-small-cell lung carcinomas (NSCLCs). Thus, inhibiting NRF2-mediated adaptive antioxidant response is widely considered a promising strategy to prevent tumor growth and reverse chemoresistance in NSCLCs. Un