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Sample records for lung carcinoma standardized

  1. [Radiotherapy for primary lung carcinoma].

    PubMed

    Giraud, P; Lacornerie, T; Mornex, F

    2016-09-01

    Indication, doses, technique of radiotherapy and concomitant chemotherapy, for primary lung carcinoma are presented. The recommendations for delineation of the target volumes and organs at risk are detailed.

  2. 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

  3. [Radiotherapy for small cell lung carcinoma].

    PubMed

    Pourel, N

    2016-10-01

    Radiotherapy for small cell lung carcinoma has known significant improvements over the past 10 years especially through routine use of PET-CT in the initial work-up and contouring before treatment. Prophylactic cranial irradiation remains a standard of care for locally advanced disease and is a subject of controversy for metastatic disease. A new indication for thoracic radiotherapy may soon arise for metastatic disease, still confirmation studies are ongoing.

  4. Recurrence of bronchioloalveolar carcinoma in transplanted lungs.

    PubMed

    Garver, R I; Zorn, G L; Wu, X; McGiffin, D C; Young, K R; Pinkard, N B

    1999-04-08

    Bronchioloalveolar carcinoma is a distinctive subtype of typical adenocarcinoma of the lung that tends to metastasize widely throughout the lungs but less commonly elsewhere. Because conventional therapies for intrapulmonary metastatic bronchioloalveolar carcinoma are generally ineffective, we treated seven patients who had intrapulmonary metastatic bronchioloalveolar carcinoma with lung transplantation. Seven patients with biopsy-proved bronchioloalveolar carcinoma and no evidence of extrapulmonary disease received transplants of either one or two cadaveric lungs. At transplantation, all native lung tissue was removed and replaced with a donor lung or lungs. The patients received the usual post-transplantation care given at the institution. Four of the seven patients had recurrent bronchioloalveolar carcinoma within the donor lungs; the recurrences appeared from 10 to 48 months after transplantation. All recurrences were limited to the donor lungs. Histologic and molecular analyses showed that the recurrent tumors in three patients originated from the recipients of the transplants. Lung transplantation for bronchioloalveolar carcinoma is technically feasible, but recurrence of the original tumor within the donor lungs up to four years after transplantation was common.

  5. Assessing Tumor-Infiltrating Lymphocytes in Solid Tumors: A Practical Review for Pathologists and Proposal for a Standardized Method from the International Immuno-Oncology Biomarkers Working Group: Part 2: TILs in Melanoma, Gastrointestinal Tract Carcinomas, Non-Small Cell Lung Carcinoma and Mesothelioma, Endometrial and Ovarian Carcinomas, Squamous Cell Carcinoma of the Head and Neck, Genitourinary Carcinomas, and Primary Brain Tumors.

    PubMed

    Hendry, Shona; Salgado, Roberto; Gevaert, Thomas; Russell, Prudence A; John, Tom; Thapa, Bibhusal; Christie, Michael; van de Vijver, Koen; Estrada, M V; Gonzalez-Ericsson, Paula I; Sanders, Melinda; Solomon, Benjamin; Solinas, Cinzia; Van den Eynden, Gert G G M; Allory, Yves; Preusser, Matthias; Hainfellner, Johannes; Pruneri, Giancarlo; Vingiani, Andrea; Demaria, Sandra; Symmans, Fraser; Nuciforo, Paolo; Comerma, Laura; Thompson, E A; Lakhani, Sunil; Kim, Seong-Rim; Schnitt, Stuart; Colpaert, Cecile; Sotiriou, Christos; Scherer, Stefan J; Ignatiadis, Michail; Badve, Sunil; Pierce, Robert H; Viale, Giuseppe; Sirtaine, Nicolas; Penault-Llorca, Frederique; Sugie, Tomohagu; Fineberg, Susan; Paik, Soonmyung; Srinivasan, Ashok; Richardson, Andrea; Wang, Yihong; Chmielik, Ewa; Brock, Jane; Johnson, Douglas B; Balko, Justin; Wienert, Stephan; Bossuyt, Veerle; Michiels, Stefan; Ternes, Nils; Burchardi, Nicole; Luen, Stephen J; Savas, Peter; Klauschen, Frederick; Watson, Peter H; Nelson, Brad H; Criscitiello, Carmen; O'Toole, Sandra; Larsimont, Denis; de Wind, Roland; Curigliano, Giuseppe; André, Fabrice; Lacroix-Triki, Magali; van de Vijver, Mark; Rojo, Federico; Floris, Giuseppe; Bedri, Shahinaz; Sparano, Joseph; Rimm, David; Nielsen, Torsten; Kos, Zuzana; Hewitt, Stephen; Singh, Baljit; Farshid, Gelareh; Loibl, Sibylle; Allison, Kimberly H; Tung, Nadine; Adams, Sylvia; Willard-Gallo, Karen; Horlings, Hugo M; Gandhi, Leena; Moreira, Andre; Hirsch, Fred; Dieci, Maria V; Urbanowicz, Maria; Brcic, Iva; Korski, Konstanty; Gaire, Fabien; Koeppen, Hartmut; Lo, Amy; Giltnane, Jennifer; Rebelatto, Marlon C; Steele, Keith E; Zha, Jiping; Emancipator, Kenneth; Juco, Jonathan W; Denkert, Carsten; Reis-Filho, Jorge; Loi, Sherene; Fox, Stephen B

    2017-08-02

    Assessment of the immune response to tumors is growing in importance as the prognostic implications of this response are increasingly recognized, and as immunotherapies are evaluated and implemented in different tumor types. However, many different approaches can be used to assess and describe the immune response, which limits efforts at implementation as a routine clinical biomarker. In part 1 of this review, we have proposed a standardized methodology to assess tumor-infiltrating lymphocytes (TILs) in solid tumors, based on the International Immuno-Oncology Biomarkers Working Group guidelines for invasive breast carcinoma. In part 2 of this review, we discuss the available evidence for the prognostic and predictive value of TILs in common solid tumors, including carcinomas of the lung, gastrointestinal tract, genitourinary system, gynecologic system, and head and neck, as well as primary brain tumors, mesothelioma and melanoma. The particularities and different emphases in TIL assessment in different tumor types are discussed. The standardized methodology we propose can be adapted to different tumor types and may be used as a standard against which other approaches can be compared. Standardization of TIL assessment will help clinicians, researchers and pathologists to conclusively evaluate the utility of this simple biomarker in the current era of immunotherapy.

  6. Treatment of lung large cell neuroendocrine carcinoma.

    PubMed

    Lo Russo, Giuseppe; Pusceddu, Sara; Proto, Claudia; Macerelli, Marianna; Signorelli, Diego; Vitali, Milena; Ganzinelli, Monica; Gallucci, Rosaria; Zilembo, Nicoletta; Platania, Marco; Buzzoni, Roberto; de Braud, Filippo; Garassino, Marina Chiara

    2016-06-01

    Lung large cell neuroendocrine carcinoma (L-LCNEC) is a rare, aggressive, and difficult-to-treat tumor. It is classified as a neuroendocrine subtype of large cell lung carcinoma (LCLC) belonging to the non-small cell lung cancer (NSCLC) group, but it is also included in the neuroendocrine tumor (NET) group. Most of the available data related to its treatment derive from retrospective analyses or small case series. For patients with L-LCNEC, prognosis is generally very poor. In early stages (I-II-III), surgery is recommended but does not seem to be sufficient. Platinum-based adjuvant chemotherapy may be useful while the role of neoadjuvant chemotherapy is still not well defined. In patients with advanced L-LCNEC, the chemotherapy regimens used in SCLC still remain the standard of treatment, but results are not satisfactory. Due to their peculiar clinical and biological features and the lack of literature data, there is an emerging need for a consensus on the best treatment strategy for L-LCNEC and for the identification of new therapeutic options. In this review, we will discuss the key aspects of L-LCNEC management with the aim to clarify the most controversial issues.

  7. Is mediastinoscopy still the gold standard to evaluate mediastinal lymph nodes in patients with non-small cell lung carcinoma?

    PubMed

    Sivrikoz, C M; Ak, I; Simsek, F S; Döner, E; Dündar, E

    2012-03-01

    In this study, we aimed to define the efficacy of F-18 FDG PET/CT for the detection of mediastinal lymph node metastases by comparing the mediastinal findings of F-18 FDG PET/CT with the histopathological results obtained either by mediastinoscopy or thoracotomy in patients with clinically operable non-small cell lung cancer (NSCLC). This is a prospective, single-institution study of 68 consecutive patients with suspected or pathologically proven, localized, clinically resectable NSCLC (8 females and 60 males; mean age: 60.36 ± 1.01 years, range: 43-78 years). The patients underwent integrated PET/CT scanning at the same PET center. Standard cervical mediastinoscopy and extended mediastinoscopy were performed to sample the lymph nodes. During thoracotomy, complete mediastinal lymph node dissection was routinely performed. Mediastinoscopy gave true positive results in 9 patients and true negative results in 57 patients. There were two false negative results. Mediastinoscopy had a sensitivity of 81.8% (95% CI: 63-82), a specificity of 100% (95% CI: 96-100), a PPV of 100% (95% CI: 77-100), a NPV of 96.6% (95% CI: 93-96), and an accuracy of 97% for the detection of mediastinal lymph node metastases. When PET/CT results were compared with postoperative pathological examination results, PET/CT correctly identified 48 out of 50 patients (96%) who did not have metastatic lymph node involvement. N2/N3 disease was correctly determined by PET/CT in 8 of 11 patients (72.7%) who had positive results on histological analysis. When only N2 and N3 nodal diseases were included in the calculation with the aim of making a comparison with mediastinoscopy (for mediastinal nodes), integrated PET/CT had a sensitivity of 72.7% (95% CI: 51-80), a specificity of 97.7% (95% CI: 92-99), a PPV of 88.9% (95% CI: 62-97), a NPV of 93.3% (95% CI: 88-95) and an accuracy of 92.6% (95% 83-95) for the detection of intrathoracic N2 and N3 nodal metastases. Our data shows that due to its high

  8. The Association Between Lung Carcinoma and Tuberculosis

    PubMed Central

    Cukic, Vesna

    2017-01-01

    Introduction: The association between lung tuberculosis and lung carcinoma is still controversial. Objective: to describe the characteristics of patients with associated lung tuberculosis (TB) and lung carcinoma (LC) in patients treated in Clinic for pulmonary diseases and TB “Podhrastovi”. Material and Methods: This is the retrospective study of patients with LC associated with TB treated in Clinic for pulmonary diseases and TB “Podhrastovi” in five-year period -from 2012 to 2016. We analyzed sex and age of patients, whether TB preceded LC or LC preceded TB, a time period between the developments of these two diseases, activity of TB, the histopathological type of LC, localization of LC in lungs (bronchial, peripheral, cavern) according to histopathological type. Results: In this period there were 2608 patients treated for LC. Among them there were 34 patients with diagnosed TB or 1.3%. All of them were smokers. No one had active TB. TB was the first diagnosis in all these patients. Each patient was previously treated for TB in hospital and had regular anti TB treatment. TB preceded LC in median time of 5 years (interquartile range 2 to 25 years). In 21 cases it was carcinoma of the drainage bronchus, in 11 cases it was peripheral lung carcinoma and 2 cases it was cavern carcinoma. Conlusion: patients with cured pulmonary tuberculosis represent a group at risk for developing lung carcinoma. Changes in the bronchial and alveolar mucosa which tuberculosis leaves behind in the lungs must be taken as a possible place of later malignant alteration. Patients with any form of pulmonary tuberculosis have to be controlled continuously.

  9. [Single prostatic metastasis of a small cell lung carcinoma].

    PubMed

    Gonzalez Yañez, Isabel; Perez Lopez, Maria Eva; Rodriguez Lopez, Jose Angel; Arias Santos, Maria Dolores; Garcia Gomez, Jesus; Garcia Mata, Jesus

    2009-03-01

    To make the difference between two uncommon entities, small cell prostate carcinoma and prostatic metastasis of small cell lung cancer. We describe a case of single extrapulmonar metastasis in the prostate from small lung carcinoma. We describe a case of single extrapulmonar metastasis in the prostate from small lung carcinoma. Clinical and radiographic findings and inmunohistochemistry allow differential diagnosis.

  10. Bilateral lung transplant for bronchioloalveolar carcinoma: first case in China.

    PubMed

    Wang, Yeming; Wei, Dong; Wang, Zhenxing; Zheng, Mingfeng; Chen, Jingyu

    2012-10-01

    Because of the potential risk of recurrence and dissemination, lung carcinoma is rarely considered an indication for lung transplant, but as the technique has improved, novel end-stage pulmonary diseases can be treated successfully. Experience in lung transplant for patients with lung carcinoma has shown that select patients may benefit from this therapy. In this report, we examine the case of a bilateral lung transplant in a young man with bilateral bronchioloalveolar carcinoma. This report suggests that bilateral lung transplant might be an efficient therapeutic option for select patients with lung carcinoma.

  11. Gastric metastasis by lung small cell carcinoma

    PubMed Central

    Casella, Giovanni; Bella, Camillo Di; Cambareri, Antonino Roberto; Buda, Carmelo Antonio; Corti, Gianluigi; Magri, Filippo; Crippa, Stefano; Baldini, Vittorio

    2006-01-01

    Metastatic tumors of the gastrointestinal tract are rare. We describe a case of gastric metastasis due to primary lung cancer, revealed by an upper gastrointestinal endoscopy (UGIE). Haematogenous metastases to the stomach are a rare event. To our knowledge, only 55 cases have been described in the international literature. In these patients, the prognosis is very poor. We report herein a case of gastric metastasis by lung small cell carcinoma, with a review of the literature about this rare entity. PMID:16810769

  12. Cytogenetic findings in thirty lung carcinoma patients.

    PubMed

    Berker-Karaüzüm, S; Lüleci, G; Ozbilim, G; Erdoğan, A; Kuzucu, A; Demircan, A

    1998-01-15

    Primary tissue cultures of human lung tumors were prepared from 30 cases of which 16 were diagnosed as squamous cell carcinoma, six adenocarcinoma, four adenosquamous cell carcinoma, three large cell carcinoma, and one small cell lung carcinoma. Chromosomal abnormalities were observed in 26 cases by cytogenetic studies with a GTG banding technique. Specific chromosome bands frequently involved in structural abnormalities were seen on 1p11, 1q11, 2p10, 6p10, 7q11, 7q22, 7q32, 8q22, 9q22, 11q11, 21q10, and Xq24. We assumed that especially i(2)(p10), i(9)(p10), i(21)(q10), t(11;12), t(14;15), del(X)(q24), and loss of the Y chromosome may play a role in the development of lung cancer as secondary changes. In this way, our cytogenetic findings provide evidence that multiple genetic lesions are associated with the pathogenesis of lung cancer.

  13. 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.

  14. [Gangliosides in the serum in lung carcinoma].

    PubMed

    Fumić, K; Vladović-Relja, T; Karada, J; Kracun, I; Stavljenić, A; Kubat, M; Cosović, C; Oberman, B

    1990-01-01

    In this study, tumor and serum gangliosides were analyzed in patients bearing lung planocellular carcinoma (LPC) before and after operative therapy. Tumor tissue, pathohistologically characterized as carcinoma planocellulare corneum (Ca. epidermoide, type 8070/3, WHO, Geneva, 1981), showed an elevated concentration of gangliosides in comparison to normal tung tissue. The composition of gangliosides in LPC tissue varied from one tumor sample to another, however, two general features were observed. First, LPC contained an increased amount of GM3 and a decreased amount of GD3 gangliosides. Second, an elevated proportion of gangliosides migrating as polysialogangliosides (x3, x5, x6) characterized the majority of LPC tissues. On the other hand, serum of patients with LPC contained an elevated amount of gangliosides (15.8 +/- 0.3 mumols/L) in comparison to control serum (6.1 +/- 0.8 mumols/L) (P less than 0.01). However, analyzing the composition of serum gangliosides by thin-layer chromatography, all serum gangliosides were more or less elevated. By day 21 after the surgical removal of LPC, serum gangliosides dropped by approximately 50% approaching the normal values. It seems that elevated serum gangliosides in LPC patients were secreted from carcinoma cells, because they normalized after surgical removal of LPC. Thus, serum gangliosides might be a useful biochemical tool for diagnosis and therapy monitoring of this carcinoma.

  15. Coronary Embolization Caused by Pleomorphic Lung Carcinoma

    PubMed Central

    Murai, Tadashi; Yonetsu, Taishi; Isobe, Mitsuaki; Kakuta, Tsunekazu

    2016-01-01

    A 73-year-old man who had been transferred to our emergency room due to sudden chest pain was diagnosed with ST-segment elevation myocardial infarction (STEMI). Primary percutaneous coronary intervention was performed. A long, white object which looked like a parasitic worm was retrieved via intracoronary aspiration and revascularization was successfully completed. Contrast computed tomography revealed a huge 7×6 cm mass in the right upper pulmonary lobe with direct pulmonary vein invasion. Histopathologic examination of the aspirated coronary object revealed pleomorphic lung carcinoma. This is an unusual case of STEMI caused by lung tumor embolization via direct pulmonary vein invasion to the left side of the heart. PMID:27980261

  16. Intranodal Palisaded Myofibroblastoma Masquerading as N2 Non-Small Cell Lung Carcinoma.

    PubMed

    Yim, Ivan H W; Will, Malcolm B; Dhaliwal, Catharine; Salter, Donald M; Walker, William S

    2016-07-01

    Intranodal palisaded myofibroblastoma is a rare and benign tumor that usually presents in the inguinal region. We report the case of a 68-year-old woman with a right paratracheal mass and right upper lobe non-small cell lung carcinoma initially staged as T1b N2 M0. After mediastinal staging, the right paratracheal mass was found to be an intranodal palisaded myofibroblastoma, which had caused erroneous upstaging of the lung carcinoma to N2 disease. This had the potential of leading to suboptimal treatment of the primary lung carcinoma if formal mediastinal staging had not been performed. To the best of our knowledge, this is the first report in the English literature of an intranodal palisaded myofibroblastoma occurring concurrently with lung cancer. This case highlights the importance of mediastinal staging in lung cancer. Mediastinoscopy remains the gold standard.

  17. Histopathological transformation to small-cell lung carcinoma in non-small cell lung carcinoma tumors

    PubMed Central

    Ruiz-Morales, José Manuel; Cano-García, Fernando

    2016-01-01

    Lung cancer is the principal cause of cancer-related death worldwide. The use of targeted therapies, especially tyrosine kinase inhibitors (TKIs), in specific groups of patients has dramatically improved the prognosis of this disease, although inevitably some patients will develop resistance to these drugs during active treatment. The most common cancer-associated acquired mutation is the epidermal growth factor receptor (EGFR) Thr790Met (T790M) mutation. During active treatment with targeted therapies, histopathological transformation to small-cell lung carcinoma (SCLC) can occur in 3–15% of patients with non-small-cell lung carcinoma (NSCLC) tumors. By definition, SCLC is a high-grade tumor with specific histological and genetic characteristics. In the majority of cases, a good-quality hematoxylin and eosin (H&E) stain is enough to establish a diagnosis. Immunohistochemistry (IHC) is used to confirm the diagnosis and exclude other neoplasia such as sarcomatoid carcinomas, large-cell carcinoma, basaloid squamous-cell carcinoma, chronic inflammation, malignant melanoma, metastatic carcinoma, sarcoma, and lymphoma. A loss of the tumor-suppressor protein retinoblastoma 1 (RB1) is found in 100% of human SCLC tumors; therefore, it has an essential role in tumorigenesis and tumor development. Other genetic pathways probably involved in the histopathological transformation include neurogenic locus notch homolog (NOTCH) and achaete-scute homolog 1 (ASCL1). Histological transformation to SCLC can be suspected in NSCLC patients who clinically deteriorate during active treatment. Biopsy of any new lesion in this clinical setting is highly recommended to rule out a SCLC transformation. New studies are trying to assess this histological transformation by noninvasive measures such as measuring the concentration of serum neuron-specific enolase. PMID:27652204

  18. Pulmonar collision tumor: metastatic adenoid cystic carcinoma and lung adenocarcinoma.

    PubMed

    Blanco, M; García-Fontán, E; Ríos, J; Rivo, J E; Fernández-Martín, R; Cañizares, M A

    2012-01-01

    We report an extraordinary case of collision tumor consisting of a lung adenocarcinoma and a metastatic adenoid cystic carcinoma in a 56 year-old man. He was diagnosed with a pulmonary nodule 11 years after treatment of an adenoid cystic carcinoma of the right maxillary sinus. A non-small cell carcinoma was observed when a transbronchial biopsy was performed. The other component of the nodule was only diagnosed with pathological examination of the resection specimen.

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

    USDA-ARS?s Scientific Manuscript database

    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...

  20. CT findings of small cell lung carcinoma

    PubMed Central

    Lee, Dongjun; Rho, Ji Young; Kang, Seunghun; Yoo, Koun Joy; Choi, Hye Jeong

    2016-01-01

    Abstract The purpose of this study was to clarify the recognizable computed tomography (CT) features of small cell lung carcinoma (SCLC). Contrast enhanced CT scans were reviewed retrospectively for mass location, mediastinal extension, and other concomitant findings in 142 patients with pathologically proven SCLC. SCLC was classified into hilar mass only (type I), hilar mass with ipsilateral mediastinal extension (type II), hilar mass with bilateral mediastinal extension (type III), and peripheral mass (type IV). When mediastinal lymphadenopathy (m-LAP) was indistinguishable from a hilar mass, we defined it as a mediastinal conglomerate mass (m-CM). Type IIa or IIIa had ipsilateral or bilateral m-LAP and type IIb, IIIb or IIIc had ipsilateral or bilateral m-CM. Type I (n = 8, 5.6%), type II (n = 58, 40.8%), type III (n = 55, 38.8%), and type IV (n = 21, 14.8%) were manifested. The combination of a hilar mass and m-CM was found in 68 patients (47.9%). Type IV masses showed lobulation in 11, microlobulation in 4, both lobulated and irregular margins in 4, and spiculation in 2. A total of 120 patients (84.5%) had a bronchial stenosis/obstruction; single (n = 52) and 2 or more (n = 68). Ninety-five patients (67.0%) had vascular invasion including main/lobar pulmonary artery and superior vena cava, and 55 (38.7%) had pleural effusion and/or pleural nodules. Concomitant parenchymal findings (n = 92, 64.8%) were noted: contiguous consolidation/nodule (n = 45), hematogeneous spread (n = 32), lymphangitic spread (n = 21), obstructive pneumonia (n = 22), and obstructive atelectasis (n = 14). In conclusion, the recognizable CT features of SCLC were a hilar mass with m-CM. Most of the hilar masses showed 2 or more bronchial stenoses/obstructions. Most cases of peripheral SCLC manifested as a lobulated mass rather than a spiculated mass. Vascular invasion and concomitant parenchymal findings were observed commonly. PMID:27893684

  1. Role of PAX-8, CD5, and CD117 in distinguishing thymic carcinoma from poorly differentiated lung carcinoma.

    PubMed

    Asirvatham, Jaya R; Esposito, Michael J; Bhuiya, Tawfiqul A

    2014-01-01

    To determine if PAX-8, CD5, and CD117 can differentiate thymic carcinoma from poorly differentiated lung carcinoma. Archived cases of thymic (n=13) and poorly differentiated lung (n=15) carcinoma were analyzed for intensity and proportion of expression of PAX-8, CD117, and CD5. PAX-8 was positive in 69.2% of thymic and 5.8% of lung carcinomas. CD117 was positive in 84% of thymic and 26.6% of lung carcinomas. A total of 53% of thymic and none of the lung carcinomas were positive for CD5. Forty-six percent, 53%, and 69% of thymic carcinomas were dual positive for combinations of CD5/PAX-8, CD117/CD5, and CD117/PAX-8, respectively. None of the lung carcinomas were dual positive. Positivity for any 2 of the 3 markers was seen in 84% of thymic and none of the lung carcinomas. Triple positivity was seen in 53% of thymic carcinomas. Adding PAX-8 to CD117 and CD5 increases the diagnostic yield for thymic carcinoma.

  2. Bilateral lung metastasectomy in carcinoma of the ampulla of Vater

    PubMed Central

    Pih, Gyu Young; Kim, Dong Kwan; Park, Kwang‐Min

    2017-01-01

    Abstract The efficacy of lung metastasectomy is well established in several cancers, including colorectal cancer. However, little is known about the result of lung metastasectomy in carcinoma of the ampulla of Vater. Only two case reports have reported the efficacy of metastasectomy in ampullary cancer patients with pulmonary metastasis. We report the result of bilateral lung metastasectomy in a patient with ampullary cancer. A 63‐year‐old woman underwent pylorus‐preserving pancreaticoduodenectomy for carcinoma of the ampulla of Vater. About three years after the surgery, two non‐calcified lung nodules in the right lower and left upper lobes had developed. Wedge resections of both lung nodules were performed and the pathological examination showed that the lung nodules were pulmonary metastases from the ampullary cancer. Ten years after the lung surgery, the patient is well and there is no evidence of recurrence. Surgical resection could be considered in patients with pulmonary metastasis from ampulla of Vater cancer, even when the metastases are bilateral. PMID:28168842

  3. Operative management of adrenal metastases from lung carcinoma.

    PubMed

    Kirsch, A J; Oz, M C; Stoopler, M; Ginsburg, M; Steinglass, K

    1993-12-01

    Most surgeons consider patients with solitary adrenal metastasis from a primary lung carcinoma incurable and avoid excision of both the adrenal and primary lung tumors. However, several cases of successful surgical management of these patients recently have been reported. We reviewed 12 surgically treated patients with isolated adrenal and lung disease and identified 2 survivors of greater than fifteen years (17%) and 4 additional patients who are still alive following combined resection (34%). This survival rate, albeit in a selected population, represents an improvement over the natural history of nine months' survival. We suggest that if after six to twelve months of following patients with lung cancer and isolated adrenal metastasis no other evidence of spread of disease is evident, the tumor biology may be favorable and resection of both adrenal and lung lesions is reasonable.

  4. Increased Sox2 copy number in lung squamous cell carcinomas

    PubMed Central

    SASAKI, HIDEFUMI; YOKOTA, KEISUKE; HIKOSAKA, YU; MORIYAMA, SATORU; YANO, MOTOKI; FUJII, YOSHITAKA

    2012-01-01

    The transcription factor Sox2 is necessary for foregut morphogenesis. Sox2 is also required for the normal development of the trachea and lung. Recently, Sox2 amplifications were investigated using large-scale single nucleotide polymorphism arrays in esophageal and lung cancer. We hypothesized that Sox2 overexpression might be correlated with clinicopathological features of lung cancers. The increased copy number of the Sox2 gene was analyzed by real-time polymerase chain reaction amplifications in 127 surgically treated non-small cell lung cancer cases from Nagoya City University Hospital, Japan. A total of 87 squamous cell carcinoma (SCC) cases were involved. An increased Sox2 gene copy number was found in 42 (33.1%) lung cancer patients. Increased Sox2 copy number status was significantly correlated with gender (females, 9.5% vs. males, 34.1%; p=0.0026), smoking status (never smoker, 4.8% vs. smoker, 32.9%; p=0.0003) and pathological subtypes (squamous cell carcinoma, 44.8% vs. non-squamous cell carcinoma, 7.5%; p<0.0001). However, among the SCCs, the Sox2 copy number status was not significantly correlated with gender, smoking status, pathological stage or differentiation status. An increased Sox2 copy number is common within SCC. PMID:22969842

  5. Carcinomas of ovary and lung with clear cell features: can immunohistochemistry help in differential diagnosis?

    PubMed

    Howell, Nicole R; Zheng, Wenxin; Cheng, Liang; Tornos, Carmen; Kane, Philip; Pearl, Michael; Chalas, Eva; Liang, Sharon X

    2007-04-01

    Metastatic lung carcinomas with clear cell morphology can be confused with primary ovarian clear cell carcinomas. We performed immunohistochemical stains in 14 cases of non-small cell lung carcinomas with clear cell features and 14 cases of ovarian clear cell carcinomas using a panel of markers, including thyroid transcription factor 1 (TTF-1), carcinoembryonic antigen (CEA), Wilms tumor gene 1, octamer-binding transcription factor 4 (OCT-4), cancer antigen 125 (CA-125), estrogen receptor, and progesterone receptor. Among non-small cell lung carcinomas with clear cell features, 87.5% of adenocarcinomas (or 50% overall frequency in lung carcinomas) were positive for TTF-1, whereas none of the ovarian clear cell carcinomas were positive (P = 0.002). All 14 ovarian clear cell carcinomas stained for CA-125 as compared with 1 non-small cell lung carcinoma (P < 0.001). On the other hand, 85% of non-small cell lung carcinomas stained for CEA, whereas none of the ovarian clear cell carcinomas did (P < 0.001). Interestingly, 4 ovarian clear cell carcinomas (28%) showed positive staining for the germ cell marker OCT-4. Either lung or ovarian carcinomas stained for Wilms tumor gene 1, estrogen receptor, or progesterone receptor very infrequently; and the difference between the 2 groups was not statistically significant. Our results suggest that an immunohistochemical panel consisting of TTF-1, CEA, CA-125, and OCT-4 is helpful in distinguishing most pulmonary and ovarian carcinomas with clear cell features.

  6. 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.

  7. [Lung resection for lung carcinoma with idiopathic interstitial pneumonia].

    PubMed

    Nakagawa, K; Yasumitsu, T; Kotake, Y; Ueshima, S; Kazuo, H; Tanemura, M; Hirabayashi, H; Ogawa, T

    1994-10-01

    Of 12 patients who underwent lung resections for lung cancer with idiopathic interstitial pneumonia (IIP), eight patients survived and four patients died due to acute exacerbation of IIP after the operation. The preoperative values for percent forced vital capacity, predicted postoperative percent vital capacity, percent one-second forced expiratory volume index and serum level of C-reactive protein were significantly different between the group of patients who survived and that of having died. Three days after the operation, the percentage of lymphocytes among leukocytes and serum level of lactate dehydrogenase in the two groups were both significantly different. These findings showed that the operative strategy for patients with lung cancer and IIP needs specifically careful consideration for operative procedure, and preoperative serum levels of C-reactive protein and postoperative lactate dehydrogenase and the percentage of lymphocytes in leukocytes would be useful in evaluation of the severity of IIP.

  8. Operative wound implantation of inflammatory sarcomatoid carcinoma of the lung.

    PubMed

    Hata, Atsushi; Sekine, Yasuo; Koh, Eitetsu; Hiroshima, Kenzo

    2014-09-01

    We describe a patient with iatrogenic chest wall implantation of inflammatory sarcomatoid carcinoma. A 43-year-old man underwent right partial lung resection for hemopneumothorax, with large bullae and an alveolar accumulation of histiocytes found on pathology. Three months later, a subcutaneous tumor appeared at a thoracoscopic port site. Needle aspiration of this tumor suggested a malignant neoplasm; therefore, a right upper lobectomy and chest wall resection were performed, and a pathologic diagnosis of sarcomatoid carcinoma was made. Pathologic reexamination of the original sample suggested that the tumor has been implanted in the patient's chest wall at the time of the first operation.

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

    PubMed

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

    2014-04-23

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

  10. Pneumopericardium as a non-small-cell lung carcinoma complication

    PubMed Central

    Kubisa, Anna; Dec, Paweł; Szewczak-Głodek, Małgorzata; Kochanowski, Leszek; Kubisa, Bartosz; Feledyk, Grzegorz; Czarnecka, Michalina; Wójcik, Janusz; Grodzki, Tomasz

    2016-01-01

    Below we present a case of a young man with symptoms of progressive weakness, fever, cough, rapid decrease in body weight and the presence of a tumor in the left axillary region. The chest radiography and echocardiography revealed gas bubbles in the pericardium. The more detailed diagnostics and computed tomography of the chest showed an infiltration of the left lung cavity and a fistula among the bronchus, pleural and pericardial cavities. Further diagnostics demonstrated that the pneumopericardium (diagnosed by means of chest radiograph and echocardiography) was a complication of a primary non-small-cell lung carcinoma. PMID:27785143

  11. Human lung small-cell carcinoma contains bombesin.

    PubMed Central

    Erisman, M D; Linnoila, R I; Hernandez, O; DiAugustine, R P; Lazarus, L H

    1982-01-01

    The presence of immunoreactive bombesin in a human lung small-cell carcinoma grown in nude mice was established by several criteria: (i) Radioimmunoassay of tissue extracts for bombesin revealed approximately 6.5 pmol/g of tissue; (ii) bombesin was found in 12-14% of the tumor cells by immunohistochemical localization; (iii) gel filtration of small-cell carcinoma extract on Sephadex G-75 and Bio-Gel P-4 gave only a single peak of immunoreactivity, which occurred at the elution volume of bombesin; and (iv) reverse-phase HPLC of acid-solubilized extracts separated the immunoreactive material into three discrete peaks, one of which eluted with a retention time identical to that of synthetic bombesin. The presence of bombesin may represent the ectopic expression of this peptide in small-cell carcinoma, because immunoreactive bombesin was found in human fetal and neonatal lung but apparently not in adult lung tissue [Wharton, J., Polak, J. M., Bloom, S. R., Ghatei, M. A., Solcia, E., Brown, M. R. & Pearse, A. G. E. (1978) Nature (London) 273, 769-770]. The immunoreactive bombesin previously found in mammalian tissues is considerably larger than amphibian bombesin; these data substantiate the presence of a mammalian form of bombesin in a human tumor that may have a structure similar to that of the amphibian peptide. Images PMID:6285381

  12. 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

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

    USDA-ARS?s Scientific Manuscript database

    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...

  14. Multiple mutations of lung squamous cell carcinoma shared common mechanisms

    PubMed Central

    Hu, Zhaoyan; Gu, Biao; Shi, Yan

    2016-01-01

    Lung squamous cell carcinoma (LUSC) is a subtype of non-small cell lung cancers which is the cause of 80% of all lung cancer deaths. The genes that highly mutated in patients with LUSC and their roles played in the tumorigenesis remains unknown. Data of patients with Lung squamous cell carcinoma (LUSC) were retrieved from The Cancer Genome Atlas (TCGA). Differentially expressed genes were identified between control and cancer samples. Patients and controls can be separated by mRNA expression level showing that the between-group variance and totally 1265 genes were differentially expressed between controls and patients. Top genes whose mutations highly occurred in patients with LUSC were identified, most of these genes were shown to be related with tumorigenesis in previous studies. All of the genes mostly mutated were independently correlated with expression levels of all genes. These mutations did not show the trend of co-occurrence. However, the influenced gene of these mutations had overlaps. After studying the intersection of these genes, a group of shared genes were identified. The shared pathways enriched which played critical role in LUSC were identified based on these shared genes. Different mutations had contribution to the progression of LUSC. Though these genes involved different specific mechanisms, most of them may share a common mechanism which is critical for LUSC. The results may suggest a neglected mechanism and also indicate a potential target for therapies. PMID:27835590

  15. 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.

  16. Genetic and molecular coordinates of neuroendocrine lung tumors, with emphasis on small-cell lung carcinomas.

    PubMed Central

    Koutsami, Marilena K.; Doussis-Anagnostopoulou, Ipatia; Papavassiliou, Athanasios G.; Gorgoulis, Vassilis G.

    2002-01-01

    The aim of this review is to present the advances in our understanding of the progression of tumorigenesis in neuroendocrine lung tumors. Current information on established and putative diagnostic and prognostic markers of neuroendocrine tumors are evaluated, with a special reference to small-cell lung carcinoma, due to its higher incidence and aggressive behavior. The genetic and molecular changes that accompany these neoplasms are highlighted, and factors that influence cell-cycle progression, apoptosis, drug resistance, and escape from immune surveillance are critically assessed. PMID:12435853

  17. 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.

  18. 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

  19. Expression of Formyl-peptide Receptors in Human Lung Carcinoma.

    PubMed

    Cattaneo, Fabio; Guerra, Germano; Parisi, Melania; Lucariello, Angela; De Luca, Antonio; De Rosa, Nicolina; Mazzarella, Gennaro; Bianco, Andrea; Ammendola, Rosario

    2015-05-01

    Formyl-peptide receptors (FPRs) are expressed in several tissues and cell types. The identification of markers involved in cell growth may further allow for molecular profiling of lung cancer. We investigated the possible role of FPRs as molecular markers in several types of lung carcinomas which is the main cause of cancer death worldwide. Tumor tissue samples were collected from six patients affected by lung cancer. Biopsies were analyzed for expression of FPR isoforms both in tumoral and peritumoral tissue by real-time polymerase chain reaction (PCR), western blot and immunofluorescence. Real-time PCR, western blot and immunofluorescence analyses showed that FPR expression is lower in types of human lung cancer tissues when compared to the surrounding peritumoral tissues. The study of the mechanistic basis for the control of FPR expression in normal peritumoral versus tumoral tissues could provide the basis for new diagnostic and therapeutic interventions. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  20. Cytomorphologic overlap of differentiated thyroid carcinoma and lung adenocarcinoma and diagnostic value of TTF-1 and TGB on cytologic material.

    PubMed

    Sathiyamoorthy, Srividya; Maleki, Zahra

    2014-01-01

    Thyroid carcinomas and lung adenocarcinoma share cytomorphological features yet have different prognoses. Thyroid Transcription Factor-1 (TTF-1) is an immunohistochemical (IHC) marker used to confirm pulmonary and thyroid carcinoma, while Thyroglobulin (TGB) is expressed by thyroid carcinoma. The cytopathology archive of The Johns Hopkins Hospital was searched for cases of lung adenocarcinoma versus thyroid carcinoma with TTF-1 and TGB IHC. Forty-four cases of lung adenocarcinoma (25) and thyroid carcinoma (19) were retrieved. One was metastatic lung adenocarcinoma to the thyroid and three were metastatic papillary thyroid carcinoma (PTC) to the lung. The initial interpretation of two cases from bony lesions was metastatic lung adenocarcinoma. In light of additional clinical information and TGB immunostain, the diagnoses of these two cases changed to metastatic thyroid carcinoma. TTF-1 and TGB is a small immunostain panel that can differentiate lung adenocarcinoma from thyroid carcinoma and prevent misdiagnosis and its consequences. Copyright © 2013 Wiley Periodicals, Inc.

  1. Human papillomavirus DNA in squamous cell carcinoma of the lung.

    PubMed Central

    Hirayasu, T; Iwamasa, T; Kamada, Y; Koyanagi, Y; Usuda, H; Genka, K

    1996-01-01

    AIM: To compare the incidence of squamous cell carcinoma (SCC) of the lung in Okinawa with that in Niigata on the mainland. METHODS: All patients presenting with SCC of the lung in Okinawa and Niigata in 1993 were included in the study. Diagnoses were confirmed by conventional histological examination of paraffin wax sections. Human papillomavirus (HPV) was detected by non-isotopic in situ hybridisation (NISH) and polymerase chain reaction (PCR) amplification with primers specific for the E6 and E7 regions of the HPV genome. PCR products were analysed by Southern and dot blotting. RESULTS: The incidence of well differentiated SCC of the lung was high in patients from Okinawa compared with moderately and poorly differentiated types, and compared with the incidence of SCC in patients from Niigata. This is despite similar patterns of age, sex (predominatly male), and smoking habit. More patients from Okinawa, however, were positive for HPV DNA by PCR (79%) and NISH (53%). Many patients haboured HPV types 6, 16, and 18. Only 30% of patients from Niigata were positive for HPV DNA by PCR and 20% by NISH. These patients all harboured one HPV type only. CONCLUSION: Surprisingly large numbers of patients from Okinawa were positive for HPV DNA. The detection of HPV DNA was strongly associated with well differentiated SCC. This was particularly true for HPV types 6 and 16. There was no correlation between either smoking and detection of HPV DNA, or smoking and histological differentiation. Images PMID:8943746

  2. Evidence, Mechanism, and Clinical Relevance of the Transdifferentiation from Lung Adenocarcinoma to Squamous Cell Carcinoma.

    PubMed

    Hou, Shenda; Zhou, Shiyu; Qin, Zhen; Yang, Liu; Han, Xiangkun; Yao, Shun; Ji, Hongbin

    2017-03-08

    Lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC) are two distinct subtypes of non-small-cell lung carcinoma. Interestingly, approximately 4% to 9% of human non-small-cell lung carcinoma tumors contain mixed adenomatous and squamous pathologies in a single lesion, clinically termed adenosquamous cell carcinoma. More important, these two different pathological components frequently share identical oncogenic mutations, indicative of a potential transition. Indeed, recent data have provided convincing evidence in supporting the ADC to SCC transdifferentiation in lungs. In the liver kinase B1 (official name STK11)-deficient mouse model, lung ADC can progressively transdifferentiate to SCC through pathologically mixed adenosquamous cell carcinoma as the intermediate status. Mechanistic studies further identify essential roles of extracellular matrix remodeling and metabolic reprogramming during this phenotypic transition. Small molecular compounds, including lysyl oxidase inhibitors and reactive oxygen species-inducing reagents such as phenformin, significantly accelerate the transition from lung ADC to SCC and thus confer lung tumors with drug resistance. Consistent with these findings, recent clinical studies have shown that epidermal growth factor receptor-mutant lung ADC can transdifferentiate to SCC in relapsed cancer patients. Together, these data support that this phenotypic transition from lung ADC to SCC might represent a novel mechanism for drug resistance. This review will summarize our current understanding of the transdifferentiation from lung ADC to SCC.

  3. USP7 overexpression predicts a poor prognosis in lung squamous cell carcinoma and large cell carcinoma.

    PubMed

    Zhao, Guang-Yin; Lin, Zong-Wu; Lu, Chun-Lai; Gu, Jie; Yuan, Yun-Feng; Xu, Feng-Kai; Liu, Rong-Hua; Ge, Di; Ding, Jian-Yong

    2015-03-01

    In non-small cell lung cancer (NSCLC), both USP7 expression and p53 gene status were reported to be an indicator of poor prognosis in adenocarcinoma patients; however, its roles and mechanisms in lung squamous cell carcinoma and large cell carcinoma need to be clarified. The USP7 expression was examined in NSCLC tumors (excluding adenocarcinoma), their corresponding non-tumorous tissues, and NSCLC cells. Then, the prognostic role of USP7 was analyzed in 110 NSCLC samples (excluding the adenocarcinoma). Finally, the roles and mechanisms of USP7 in the proliferation, metastasis, and invasion of a NSCLC cell were assessed using a specific vshRNA. The USP7 expression was higher in NSCLC tissues compared to non-tumorous samples, accordingly, the high level of USP7 was detected in NSCLC cell lines compared with HBE cell. After the USP7 downregulation, the H460 cells exhibited decreased metastasis/invasion in vitro and in vivo. The preliminary mechanism study indicated overexpression of USP7 might regulate the p53-MDM2 pathway by inducing the MDM2 de-ubiquitination and subsequent stabilization, which resulted in the upregulation of the Bad phosphorylation. Additionally, we also found that USP7 might induce cell epithelial-mesenchymal transition to enhance the cell invasive ability. Clinically, USP7 overexpression significantly correlated with malignant phenotype. Furthermore, the 5-year overall survival in patients with USP7(low) was higher than that of USP7(high). Multivariate analysis showed USP7 overexpression was an independent prognostic marker for these cancers. USP7 overexpression may regulate the survival and invasive properties of squamous cell carcinoma and large cell carcinoma cells, and may serve as a molecular target.

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

    PubMed Central

    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

    2016-01-01

    To compare lung adenocarcinoma (ADC) and lung squamous cell carcinoma (SqCC) and to identify new drivers of lung carcinogenesis, we examined 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 other squamous carcinomas than to lung ADCs. Novel significantly mutated genes included PPP3CA, DOT1L, and FTSJD1 in lung ADC, RASA1 in lung SqCC, and KLF5, EP300, and CREBBP in both tumor types. Novel amplification peaks encompassed MIR21 in lung ADC, MIR205 in lung SqCC, and MAPK1 in both. Lung ADCs lacking receptor tyrosine kinase/Ras/Raf alterations revealed mutations in SOS1, VAV1, RASA1, and ARHGAP35. Regarding neoantigens, 47% of the lung ADC and 53% of the lung SqCC tumors had at least 5 predicted neoepitopes. While targeted therapies for lung ADC and lung SqCC are largely distinct, immunotherapies may aid in treatment for both subtypes. PMID:27158780

  5. 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.

  6. 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.

  7. 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

  8. Betulin inhibits lung carcinoma proliferation through activation of AMPK signaling.

    PubMed

    Li, Xian-Dong; Zhang, Yi-Jie; Han, Ji-Chang

    2014-11-01

    Betulin (lup-20(29)-ene-3β, 28-diol) is an abundant, naturally occurring triterpene. It is commonly isolated from the bark of birch trees and forms up to 30% of the dry weight of the extractive. In the present study, we revealed its antiproliferative effects and mechanisms using two lung carcinoma cells (A549 and NCI-292). By 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and bromodeoxyuridine (BrdU) incorporation assays, we found that betulin could efficiently inhibit cell growth and proliferation. Besides, several key genes of cell-cycle regulators were also affected by betulin treatment. At the molecular level, our results demonstrated that treatment with betulin was also associated with activation of AMP kinase and inhibition of mTOR/p70S6K/pS6 signaling in these cells. In agreement, inhibition of AMPK signaling largely reversed the antiproliferative roles of betulin. Taken together, these data provide evidence for a mechanism that may contribute to the antineoplastic effects of betulin and justify further work to explore its potential roles in lung cancer prevention and treatment.

  9. Reticular erythematous mucinosis (REM) with telangiectasias associated with essential thrombocytosis and lung carcinoma.

    PubMed

    Leon-Mateos, Alvaro; Ginarte, Manuel; León, Luis; Toribio, Jaime

    2005-01-01

    The cutaneous mucinoses are a heterogeneous group of diseases in which mucin accumulates in the skin. Reticular erythematous mucinosis (REM) is an infrequent variant. We present a 48-year-old man with essential thrombocytosis and REM lesions with atypical telangiectasias on his chest, who developed a non-small cell lung carcinoma. We discuss the unusual clinical finding of telangiectasias over REM lesions and the association with essential thrombocytosis and lung carcinoma.

  10. [Cytology of basaloid squamous cell carcinoma and small cell carcinoma of lung: a comparative study].

    PubMed

    He, S R; Bai, Y P; Gong, H; Di, J; Chen, L; Dai, W D; Hu, S T; Liu, D G

    2016-04-08

    To evaluate the roles of cytomorphology and immunohistochemistry in distinguishing between basaloid squamous cell carcinoma (BSC) and small cell carcinoma (SCC) of lung. The direct smears and/or liquid-based cytology preparation (ThinPrep) of bronchial brushing/washing and fine-needle aspiration (FNA) specimens from 17 cases of biopsy-proven BSC of lung were retrospectively reviewed and compared with those from 17 cases of SCC. The cytomorphologic parameters analyzed included proportion of cohesive cell clusters, cell palisades/rosettes, adenoid cystic features, crushing artifact, nuclear maximum diameter, nuclear molding, scantiness of cytoplasm,"salt-and-pepper"nuclei, distinct nucleoli, spindly configuration, individual cell keratinization, necrosis, hyaline material, apoptosis and mitotic activity. Immunocytochemical/immunohistochemical study of 25 cases was performed. Ten FNA samples of basaloid squamous cell carcinoma were also analyzed for epidermal growth factor receptor mutations in exons 18, 19, 20 and 21 using amplification refractory mutation system. Most of the 17 BSC cases (15/17) showed a predominance of tightly cohesive tumor cell clusters. The proportion of isolated tumor cells was high in SCC (more than 60% in 14 cases). The nuclear maximum diameter of BSC was slightly larger than that of SCC (9 to 11 μm in BSC versus 7 to 9 μm in SCC)."Salt-in-pepper"nuclei, nuclear molding and crushing artifact were detected in all SCC cases (15/17, 17/17 and 14/17, respectively). These features were only occasionally found in BSC group. Nucleoli were present in BSC and rarely (2/17) in SCC. Only 9 of 17 BSC cases showed individual cell keratinization. The differences in the above-mentioned cytomorphologic features were statistically significance (P<0.05). The results of immunohistochemistry performed on the cell block sections and immunocytochemistry performed on the ThinPrep slides were identical to that performed on the corresponding biopsy specimens. The

  11. Transdifferentiation of lung adenocarcinoma in mice with Lkb1 deficiency to squamous cell carcinoma

    PubMed Central

    Han, Xiangkun; Li, Fuming; Fang, Zhaoyuan; Gao, Yijun; Li, Fei; Fang, Rong; Yao, Shun; Sun, Yihua; Li, Li; Zhang, Wenjing; Ma, Huimin; Xiao, Qian; Ge, Gaoxiang; Fang, Jing; Wang, Hongda; Zhang, Lei; Wong, Kwok-kin; Chen, Haiquan; Hou, Yingyong; Ji, Hongbin

    2014-01-01

    Lineage transition in adenocarcinoma (ADC) and squamous cell carcinoma (SCC) of non-small cell lung cancer, as implicated by clinical observation of mixed ADC and SCC pathologies in adenosquamous cell carcinoma, remains a fundamental yet unsolved question. Here we provide in vivo evidence showing the transdifferentiation of lung cancer from ADC to SCC in mice: Lkb1-deficient lung ADC progressively transdifferentiates into SCC, via a pathologically mixed mAd-SCC intermediate. We find that reduction of lysyl oxidase (Lox) in Lkb1-deficient lung ADC decreases collagen disposition and triggers extracellular matrix remodelling and upregulates p63 expression, a SCC lineage survival oncogene. Pharmacological Lox inhibition promotes the transdifferentiation, whereas ectopic Lox expression significantly inhibits this process. Notably, ADC and SCC show differential responses to Lox inhibition. Collectively, our findings demonstrate the de novo transdifferentiation of lung ADC to SCC in mice and provide mechanistic insight that may have important implications for lung cancer treatment. PMID:24531128

  12. Hypercalcemia-leukocytosis syndrome in a patient with cavitating squamous cell carcinoma of the lung

    PubMed Central

    2009-01-01

    Introduction Lung cancer is the leading cause of death among the cancers seen in the United States. Hypercalcemia and leukocytosis are two common paraneoplastic syndromes associated with lung cancer. Unfortunately patients presenting with Hypercalcemia- leukocytosis syndrome has a worse prognosis than patients presenting with lung cancer alone. Case presentation We present a 67 yr old Caucasian male with a history of active smoking presenting as pneumonia being diagnosed as cavitating squamous cell carcinoma of the lung with hypercalcemia-leukocytosis syndrome Conclusion There should be a high degree of suspicion to diagnose lung cancer in patients presenting with symptoms of paraneoplastic syndrome. PMID:19183491

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

    Cancer.gov

    In the U.S. lung cancer remains the most deadly cancer type with less than one in five patients alive five years after diagnosis. The majority of lung cancer deaths are due to tobacco smoke, and the squamous cell carcinoma (SCC) subtype of lung cancer is strongly associated with smoking. Researchers have identified a number of mutations in lung SCC tumors but have failed to generate an animal model of lung SCC, which is critical for understanding the biology of the disease and for identifying novel therapeutic targets.

  14. Comparative characterization of pulmonary surfactant aggregates and alkaline phosphatase isozymes in human lung carcinoma tissue.

    PubMed

    Iino, Nozomi; Matsunaga, Toshiyuki; Harada, Tsuyoshi; Igarashi, Seiji; Koyama, Iwao; Komoda, Tsugikazu

    2007-05-01

    Alkaline phosphatase (AP) isozymes are surfactant-associated proteins (SPs). Since several different AP isozymes have been detected in the pneumocytes of lung cancer patients, we attempted to identify the relationship between pulmonary surfactant aggregate subtypes and AP isozymes. Pulmonary surfactant aggregates were isolated from carcinoma and non-carcinoma tissues of patients with non-small cell carcinoma of the lung. Upon analysis, ultraheavy, heavy, and light surfactant aggregates were detected in the non-carcinoma tissues, but no ultraheavy surfactant aggregates were found in the carcinoma tissues. Surfactant-associated protein A (SP-A) was detected as two bands (a 27-kDa band and a 54-kDa band) in the ultraheavy, heavy, and light surfactant aggregates found in the non-carcinoma tissues. Although both SP-A bands were detected in the heavy and light surfactant aggregates from adenocarcinoma tissues, the 54-kDa band was not detected in squamous cell carcinoma tissues. Liver AP (LAP) was detected in the heavy and light surfactant aggregates from both non-carcinoma and squamous carcinoma tissues, but not in heavy surfactant aggregates from adenocarcinoma tissues. A larger amount of bone type AP (BAP) was found in light surfactant aggregate fractions from squamous cell carcinomas than those from adenocarcinoma tissues or non-carcinoma tissues from patients with either type of cancer. LAP, BAP, and SP-A were identified immunohistochemically in type II pneumocytes from non-carcinoma tissues and adenocarcinoma cells, but no distinct SP-A staining was observed in squamous cell carcinoma tissues. The present study has thus revealed several differences in pulmonary surfactant aggregates and AP isozymes between adenocarcinoma tissue and squamous cell carcinoma tissue.

  15. 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

  16. Differentiating head and neck carcinoma from lung carcinoma with an electronic nose: a proof of concept study.

    PubMed

    van Hooren, Michel R A; Leunis, Nicoline; Brandsma, Dirk S; Dingemans, Anne-Marie C; Kremer, Bernd; Kross, Kenneth W

    2016-11-01

    Disease specific patterns of volatile organic compounds can be detected in exhaled breath using an electronic nose (e-nose). The aim of this study is to explore whether an e-nose can differentiate between head and neck, and lung carcinoma. Eighty-seven patients received an e-nose measurement before any oncologic treatment. We used PARAFAC/TUCKER3 tensor decomposition for data reduction and an artificial neural network for analysis to obtain binary results; either diagnosed as head and neck or lung carcinoma. Via a leave-one-out method, cross-validation of the data was performed. In differentiating head and neck from lung carcinoma patients, a diagnostic accuracy of 93 % was found. After cross-validation of the data, this resulted in a diagnostic accuracy of 85 %. There seems to be a potential for e-nose as a diagnostic tool in HNC and lung carcinoma. With a fair diagnostic accuracy, an e-nose can differentiate between the two tumor entities.

  17. Whole exome sequencing of independent lung adenocarcinoma, lung squamous cell carcinoma, and malignant peritoneal mesothelioma

    PubMed Central

    Vanni, Irene; Coco, Simona; Bonfiglio, Silvia; Cittaro, Davide; Genova, Carlo; Biello, Federica; Mora, Marco; Rossella, Valeria; Dal Bello, Maria Giovanna; Truini, Anna; Banelli, Barbara; Lazarevic, Dejan; Alama, Angela; Rijavec, Erika; Barletta, Giulia; Grossi, Francesco

    2016-01-01

    Abstract The presence of multiple primary tumors (MPT) in a single patient has been identified with an increasing frequency. A critical issue is to establish if the second tumor represents an independent primary cancer or a metastasis. Therefore, the assessment of MPT clonal origin might help understand the disease behavior and improve the management/prognosis of the patient. Herein, we report a 73-year-old male smoker who developed 2 primary lung cancers (adenocarcinoma and squamous cell carcinoma) and a malignant peritoneal mesothelioma (PM). Whole exome sequencing (WES) of the 3 tumors and of germline DNA was performed to determine the clonal origin and identify genetic cancer susceptibility. Both lung cancers were characterized by a high mutational rate with distinct mutational profiles and activation of tumor-specific pathways. Conversely, the PM harbored a relative low number of genetic variants and a novel mutation in the WT1 gene that might be involved in the carcinogenesis of nonasbestos-related mesothelioma. Finally, WES of the germinal DNA displayed several single nucleotide polymorphisms in DNA repair genes likely conferring higher cancer susceptibility. Overall, WES did not disclose any somatic genetic variant shared across the 3 tumors, suggesting their clonal independency; however, the carcinogenic effect of smoke combined with a deficiency in DNA repair genes and the patient advanced age might have been responsible for the MPT development. This case highlights the WES importance to define the clonal origin of MPT and susceptibility to cancer. PMID:27902597

  18. Predictive and prognostic value of preoperative serum tumor markers in resectable adenosqamous lung carcinoma

    PubMed Central

    Yue, Dongsheng; Li, Kai; Jiang, Richeng

    2016-01-01

    Background Adenosquamous carcinoma is a rare and aggressive form of lung cancer. The prognostic and predictive value of preoperative serum tumor markers and frequency of EGFR mutations in adenosquamous lung carcinoma are unclear. Methods We retrospectively analyzed data and samples collected from 106 radically resected adenosquamous lung carcinoma patients with pathological stage I-IIIA between 2008 and 2013. Correlations between serum tumor marker levels and EGFR mutations as well as survival parameters were analyzed and prognostic factors were identified. Results Of the 106 adenosquamous lung carcinoma patients, 29 (27.4%) harbored EGFR mutations. By univariate analysis, advanced clinical stage (P = 0.009 for disease-free survival [DFS]; P = 0.046 for overall survival [OS]), larger tumor size (P = 0.001 for DFS; P = 0.002 for OS), regional lymph node metastasis (P = 0.024 for DFS; P = 0.030 for OS), higher NSE level (P = 0.002 for DFS; P < 0.001 for OS), and higher TMI (tumor marker index) (P = 0.009 for OS) were significantly correlated with a worse prognosis. By multivariate analysis, NSE (P = 0.014) was confirmed as independent predictor for DFS, while NSE (P = 0.001) and TMI (P = 0.038) were independent prognostic factors for OS. Conclusion Adenosquamous lung carcinoma is an aggressive malignancy with relatively high EGFR mutation frequency. Elevated preoperative NSE level and TMI are adverse predictive and prognostic indicators. PMID:27623437

  19. 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.

  20. Morphologic Accuracy in Differentiating Primary Lung Adenocarcinoma From Squamous Cell Carcinoma in Cytology Specimens

    PubMed Central

    Zakowski, Maureen F.; Rekhtman, Natasha; Auger, Manon; Booth, Christine N.; Crothers, Barbara; Ghofrani, Mohiddean; Khalbuss, Walid; Laucirica, Rodolfo; Moriarty, Ann T.; Tabatabai, Z. Laura; Barkan, Güliz A.

    2017-01-01

    Context The National Cancer Care Network and the combined College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology guidelines indicate that all lung adenocarcinomas (ADCs) should be tested for epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements. As the majority of patients present at a later stage, the subclassification and molecular analysis must be done on cytologic material. Objective To evaluate the accuracy and interobserver variability among cytopathologists in subtyping non–small cell lung carcinoma using cytologic preparations. Design Nine cytopathologists from different institutions submitted cases of non–small cell lung carcinoma with surgical follow-up. Cases were independently, blindly reviewed by each cytopathologist. A diagnosis of ADC or squamous cell carcinoma was rendered based on the Diff-Quik, Papanicolaou, and hematoxylin-eosin stains. The specimen types included fine-needle aspiration from lung, lymph node, and bone; touch preparations from lung core biopsies; bronchial washings; and bronchial brushes. A major disagreement was defined as a case being misclassified 3 or more times. Results Ninety-three cases (69 ADC, 24 squamous cell carcinoma) were examined. Of 818 chances (93 cases × 9 cytopathologists) to correctly identify all the cases, 753 correct diagnoses were made (92% overall accuracy). Twenty-five of 69 cases of ADC (36%) and 7 of 24 cases of squamous cell carcinoma (29%) had disagreement (P = .16). Touch preparations were more frequently misdiagnosed compared with other specimens. Diagnostic accuracy of each cytopathologist varied from 78.4% to 98.7% (mean, 91.7%). Conclusion Lung ADC can accurately be distinguished from squamous cell carcinoma by morphology in cytologic specimens with excellent interobserver concordance across multiple institutions and levels of cytology experience. PMID:27552093

  1. Effect of delays on survival in patients with lung carcinoma in Montenegro.

    PubMed

    Živković, Danko

    2014-12-01

    Lung cancer is a global medical problem with a rising incidence and 5-year survival of 5%-10%. The aim of this study was to investigate whether waiting times and delays in diagnosis and treatment of patients with lung carcinoma have any bearing on prognosis and survi- val. The study was performed in the Brezovik Special Hospital for Lung Diseases and Tuberculosis. The study included all cases with the diagnosis of lung carcinoma in the Republic of Montenegro in 2009, a total of 206 patients, with follow up until the end of 2010. Median age was 66, median Karnofsky score 80, and male to female ratio 5:1. Diagnostic procedure was bronchoscopy in 89% of patients. Histologic type was small cell lung cancer in 25.7% and non small cell lung cancer in 74.3% of cases. Surgery was the main treatment for 24.4% of patients. Median delay from first symptoms to diagnosis of lung cancer was 10.35 weeks, mean 8 weeks (median patient's delay was 6.20 weeks, doctor's delay at primary health care 2.07 weeks and in pulmonology services 2.37 weeks). Median survival time for all patients was 39.27 weeks, mean 34. There was no statistically significant diffe- rence between patient's delay/doctor's delay/total delay and stage of lung carcinoma at the time of diagnosis, treatment choice and survival. Our results indicate that longer delay is not associated with poorer prognosis of lung carcinoma. The possible ways of reducing mortality of lung cancer include prevention by decreasing smoking prevalence and improved therapeutic options.

  2. 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.

  3. Clinical Outcome of Patients Transplanted with Marginal Donor Lungs via Ex Vivo Lung Perfusion Compared to Standard Lung Transplantation.

    PubMed

    Fildes, James E; Archer, Louise D; Blaikley, John; Ball, Alexandra L; Stone, John P; Sjöberg, Trygve; Steen, Stig; Yonan, Nizar

    2015-05-01

    Lung transplantation is limited by a scarcity of suitable donors resulting in high waiting list mortality. Ex vivo lung perfusion (EVLP) allows the evaluation and reconditioning of marginal donor lungs for use in transplantation. This study aimed to compare clinical outcome of patients transplanted with marginal organs by means of EVLP with a standard lung transplant cohort through a multicenter open trial. Group 1 (n = 9) included patients transplanted using EVLP reconditioned marginal lungs. Group 2 (n = 46) consisted of date-matched patients transplanted using standard transplantation of acceptable lungs. The primary composite endpoint included acute rejection and infection at 12 months after transplantation. There was no significant difference in the overall incidence of acute rejection (P = 0.754) and the number of treated infection episodes (proven/probable pneumonia; P = 0.857/0.368 and proven/probable tracheobronchitis; P = 0.226/0.529) up to 12 months after transplantation, between group 1 and group 2. Additionally, there was no significant difference in early clinical outcome, including intensive care unit stay, hospital stay, and 1 year mortality between the two groups (P = 0.338, P = 0.112 and P = 0.372, respectively). This multicenter study demonstrates that EVLP is associated with no adverse effect on clinical outcome, including the incidence of acute rejection and infection after lung transplantation.

  4. Standardizing CT lung density measure across scanner manufacturers.

    PubMed

    Chen-Mayer, Huaiyu Heather; Fuld, Matthew K; Hoppel, Bernice; Judy, Philip F; Sieren, Jered P; Guo, Junfeng; Lynch, David A; Possolo, Antonio; Fain, Sean B

    2017-03-01

    Computed Tomography (CT) imaging of the lung, reported in Hounsfield Units (HU), can be parameterized as a quantitative image biomarker for the diagnosis and monitoring of lung density changes due to emphysema, a type of chronic obstructive pulmonary disease (COPD). CT lung density metrics are global measurements based on lung CT number histograms, and are typically a quantity specifying either the percentage of voxels with CT numbers below a threshold, or a single CT number below which a fixed relative lung volume, nth percentile, falls. To reduce variability in the density metrics specified by CT attenuation, the Quantitative Imaging Biomarkers Alliance (QIBA) Lung Density Committee has organized efforts to conduct phantom studies in a variety of scanner models to establish a baseline for assessing the variations in patient studies that can be attributed to scanner calibration and measurement uncertainty. Data were obtained from a phantom study on CT scanners from four manufacturers with several protocols at various tube potential voltage (kVp) and exposure settings. Free from biological variation, these phantom studies provide an assessment of the accuracy and precision of the density metrics across platforms solely due to machine calibration and uncertainty of the reference materials. The phantom used in this study has three foam density references in the lung density region, which, after calibration against a suite of Standard Reference Materials (SRM) foams with certified physical density, establishes a HU-electron density relationship for each machine-protocol. We devised a 5-step calibration procedure combined with a simplified physical model that enabled the standardization of the CT numbers reported across a total of 22 scanner-protocol settings to a single energy (chosen at 80 keV). A standard deviation was calculated for overall CT numbers for each density, as well as by scanner and other variables, as a measure of the variability, before and after the

  5. [Suppression of WIFI transcript and protein in non-small cell lung carcinomas].

    PubMed

    Korobko, E V; Kalinichenko, S V; Shepelev, M V; Zborovskaia, I B; Allakhverdiev, A K; Zinov'eva, M V; Vinogradova, T V; Sverdlov, E D; Korobko, I V

    2007-01-01

    Changes in WIFI expression, an extracellular inhibitor of Wnt pathway, in non-small cell lung carcinomas were analyzed. Frequent (67% cases) suppression of WIFI transcript in non-small cell lung carcinomas were found. Our results, together with previously published data, suggest that inhibition of WIFI expression often occurs in squamous cell carcinomas and is less typical of adenocarcinomas. It was also found that a decrease in the WIFI transcript in tumors is parallel to concomitant suppression of the WIFI protein level. Our results provide further evidence that the WIFI suppression is a frequent event in the lung carcinogenesis, which might lead to disregulation of Wnt signaling pathway and contribute to tumor progression.

  6. Gene expression profiling allows distinction between primary and metastatic squamous cell carcinomas in the lung.

    PubMed

    Talbot, Simon G; Estilo, Cherry; Maghami, Ellie; Sarkaria, Inderpal S; Pham, Duy Khanh; O-charoenrat, Pornchai; Socci, Nicholas D; Ngai, Ivan; Carlson, Diane; Ghossein, Ronald; Viale, Agnes; Park, Bernard J; Rusch, Valerie W; Singh, Bhuvanesh

    2005-04-15

    Lung neoplasms commonly develop in patients previously treated for head and neck carcinomas. The derivation of these tumors, either as new primary lung cancers or as metastatic head and neck cancers, is difficult to establish based on clinical or histopathologic criteria since both are squamous cell carcinomas and have identical features under light microscopy. However, this distinction has significant treatment and prognostic implications. Gene expression profiling was performed on a panel of 52 sequentially collected patients with either primary lung (n = 21) or primary head and neck (n = 31) carcinomas using the Affymetrix HG_U95Av2 high-density oligonucleotide microarray. Unsupervised hierarchical clustering with Ward linkage and the Pearson correlation metric was performed. To assess robustness, bootstrap resampling was performed with 1,000 iterations. A t test of the normalized values for each gene was used to determine the genes responsible for segregating head and neck from lung primary carcinomas, and those with the most differential expression were used for later analyses. In the absence of a large "test" set of tumors, we used a supervised leave-one-out cross-validation to test how well we could predict the tumor origin. Once a gene expression profile was established, 12 lung lesions taken from patients with previously treated head and neck cancers were similarly analyzed by gene expression profiling to determine their sites of origin. Unsupervised clustering analysis separated the study cohort into two distinct groups which reliably remained segregated with bootstrap resampling. Group 1 consisted of 30 tongue carcinomas. Group 2 consisted of 21 lung cancers and 1 tongue carcinoma. The clustering was not changed even when normal lung or tongue profiles were subtracted from the corresponding carcinomatous lesions, and a leave-one-out cross-validation showed a 98% correct prediction (see Supplementary Data 1). A minimum set of 500 genes required to

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

    USDA-ARS?s Scientific Manuscript database

    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...

  8. [Therapeutic management of poorly differentiated neuroendocrine lung tumors and neuroendocrine carcinomas of the digestive system].

    PubMed

    Pellat, Anna; Wislez, Marie; Svrcek, Magali; Hammel, Pascal; Afchain, Pauline; André, Thierry

    2016-10-01

    Poorly differentiated neuroendocrine tumors are rare but their incidence is rising. High-grade neuroendocrine lung tumors, including small-cell lung cancer, are part of this group. Outside of the lung, they most often arise within the gastrointestinal tract (oesophagus, guts and pancreas) and are called neuroendocrine carcinomas. Due to their rarity, very little is known about neuroendocrine carcinomas of the pancreas and the gastrointestinal tract and few studies have been done. Therefore, most therapeutic recommendations are issued from studies on small-cell lung cancers. Histological scores have grown more accurate these past few years: poorly differentiated neuroendocrine tumors regroup various entities such as small-cells, large-cells and mix tumors, which seem to have different prognosis. They are diagnosed at a metastatic state in more than 50 % of cases. In localised disease, surgery is performed on selected patients. Adjuvant chemotherapy is administered in poorly differentiated neuroendocrine tumors of the lung and is an option in neuroendocrine carcinomas, without proof of efficacy. If not operable, radiochemotherapy is done for tumors of the lung, rectum, and eosophagus. If the disease is diagnosed at a metastatic state, chemotherapy is administered with a combination of platin salts (cisplatin or carboplatin) and etoposide. In poorly differentiated neuroendocrine tumors of the lung, prophylactic cranial irradiation is performed in localized disease if there is a good response to chemotherapy. Even if these therapies have improved the overall survival, no improvement has been made during the past four decades and the prognosis remains low.

  9. [The scintigraphic prediction of residual lung function after lobectomy in patients with bronchial carcinoma].

    PubMed

    Giordano, A; Calcagni, M L; Rossi, B; D'Ugo, D; Corbo, G M; Fumagalli, G; Valente, S; D'Andrea, G; Galli, G

    1995-04-01

    The scintigraphic prediction of residual pulmonary function after pneumonectomy has been validated in a number of studies while scintigraphy is not standardized in case of lobectomy. This study was aimed at investigating the accuracy of the scintigraphic prediction of post-lobectomy lung function using Wernly method. We examined 43 patients with bronchial carcinoma: 20 of them underwent pneumonectomy and 23 underwent lobectomy. The pulmonary function data (vital capacity, CV, and forced expiratory volume in one second, VEMS) predicted by quantitative lung scan were compared with those observed in the postoperative follow-up. A good correlation between predicted and observed data was obtained in both the pneumonectomized group (r = 0.77 and 0.78 for CV and VEMS, respectively; p < 0.005) and the lobectomized group (r = 0.74 and 0.79 for CV and VEMS, respectively: p < 0.005). It can be concluded that the method used for the scintigraphy prediction of post-lobectomy pulmonary function is as accurate as the post-pneumonectomy method and can be used reliably in the clinical practice.

  10. 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.

  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.

  12. Diagnostic accuracies of clinical studies in patients with small cell carcinoma of the lung

    SciTech Connect

    Chak, L.Y.; Paryani, S.B.; Sikic, B.I.; Lockbaum, P.; Torti, F.M.; Carter, S.K.

    1983-05-01

    The diagnostic accuracy of clinical studies done in 38 patients with small cell carcinoma of the lung was analyzed by comparing the test results to autopsy findings. The chest radiograph was accurate in 31 of 38 patients (82%). The accuracy of the chest radiograph was higher in evaluating the lung parenchyma and mediastinum than in evaluating the hilum and pleura. Computerized tomographic brain scan was accurate in 11 of 12 patients. However, all the diagnostic studies used for assessing the liver, including physical examination, serum liver enzyme and bilirubin measurements, and radionuclide liver scan, were only moderately accurate. More accurate studies for detecting liver metastasis in patients with small cell carcinoma are needed.

  13. β3 integrin expression is required for invadopodia-mediated ECM degradation in lung carcinoma cells

    PubMed Central

    Morales, Xabier; Salvo, Elizabeth; Garasa, Saray; Ortiz de Solórzano, Carlos; Martínez, Alfredo; Larrayoz, Ignacio M.; Rouzaut, Ana

    2017-01-01

    Cancer related deaths are primarily due to tumor metastasis. To facilitate their dissemination to distant sites, cancer cells develop invadopodia, actin-rich protrusions capable of degrading the surrounding extracellular matrix (ECM). We aimed to determine whether β3 integrin participates in invadopodia formed by lung carcinoma cells, based on our previous findings of specific TGF-β induction of β3 integrin dependent metastasis in animal models of lung carcinoma. In this study, we demonstrate that lung carcinoma cells form invadopodia in response to TGF-β exposure. Invadopodia formation and degradation activity is dependent on β3 integrin expression since β3 integrin deficient cells are not able to degrade gelatin-coated surfaces. Even more, transient over-expression of SRC did not restore invadopodia formation in β3 integrin deficient cells. Finally, we observed that blockade of PLC-dependent signaling leads to more intense labeling for β3 integrin in invadopodia. Our results suggest that β3 integrin function, and location, in lung cancer cells are essential for invadopodia formation, and this integrin regulates the activation of different signal pathways necessary for the invasive structure. β3 integrin has been associated with poor prognosis and increased metastasis in several carcinoma types, including lung cancer. Our findings provide new evidence to support the use of targeted therapies against this integrin to combat the onset of metastases. PMID:28767724

  14. CpG-ODN increases the release of VEGF in a mouse model of lung carcinoma.

    PubMed

    Sorrentino, Rosalinda; Morello, Silvana; Giordano, Maria Grazia; Arra, Claudio; Maiolino, Piera; Adcock, Ian M; Pinto, Aldo

    2011-06-15

    Vascular endothelial-derived growth factor (VEGF) plays a fundamental role in the formation of new vessels within the tumour mass. Increasing evidence has highlighted the involvement of Toll-like receptors (TLRs) in cancer. Of interest, TLR9 is over-expressed in human lung carcinoma tissues. The aim of our study was to determine whether TLR9 activation could alter VEGF release in a mouse model of lung carcinoma. Lewis lung carcinoma cells were intravenously (i.v.) inoculated and 10 days later, tumour-bearing mice were treated with CpG-ODN (CpG, a TLR9 ligand) or PBS. CpG administration enhanced VEGF release, which was associated with increased tumour lesions in the lung. CpG induced high levels of IL-6 expression and activation of STAT3 in tumour-bearing mice. Moreover, CpG induced VEGF release from primary fibroblasts and endothelial cells, which correlated with IL-6 and TGFβ production. This may explain the large influx of fibroblasts and the production of basic fibroblast growth factor (bFGF) in the tumour mass. The administration of a monoclonal antibody against VEGF A arrested tumour progression and induced a Th1-like response in CpG-treated tumour-bearing mice. In conclusion, our study demonstrates that the combination of CpG with anti-VEGF monoclonal antibody could be of potential therapeutic in lung carcinoma.

  15. The challenge of measuring lung structure. On the "Standards for the Quantitative Assessment of Lung Structure".

    PubMed

    Weibel, Ewald R

    2010-09-01

    The purpose of this review is to call attention of respiratory scientists to an Official Policy Statement jointly issued by the American Thoracic Society and the European Respiratory Society on "Standards for the Quantitative Assessment of Lung Structure", based on an extended report of a joint task force of 20 experts, and recently published in the Am. J. Respir. Crit. Care Med. This document provides investigators of normal and diseased lung structure with a review of the stereological methods that allow measurements to be done on sections. It critically discusses the preparation procedures, the conditions for unbiased sampling of the lung for microscopic study, and the potential applications of such methods. Here we present some case studies that underpin the importance of using accurate methods of structure quantification and outline paths into the future for structure-function studies on lung diseases.

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

    PubMed

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

    2016-04-29

    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. 2016 BMJ Publishing Group Ltd.

  17. Patterns of interstitial lung disease during everolimus treatment in patients with metastatic renal cell carcinoma.

    PubMed

    Mizuno, Ryuichi; Asano, Koichiro; Mikami, Shuji; Nagata, Hirohiko; Kaneko, Gou; Oya, Mototsugu

    2012-05-01

    To elucidate the patterns of interstitial lung disease during everolimus treatment in patients with metastatic renal cell carcinoma, we reviewed seven cases of everolimus-induced interstitial lung disease. Seven patients with metastatic renal cell carcinoma, which continued to progress despite treatment with sunitinib or sorafenib, developed interstitial lung disease after treatment with everolimus. Chest X-ray demonstrated diffuse infiltrates in lung fields, and chest computed tomography showed bilateral reticular and ground-glass opacities. Serum levels of lactate dehydrogenase (7/7), C-reactive protein (6/7), pulmonary surfactant associated protein D (1/7) and Krebs von den Lungen 6 (5/7) were elevated. The bronchoalveolar lavage fluid obtained from four patients with Grade 3 interstitial lung disease showed lymphocytosis. The transbronchial lung biopsy specimens showed interstitial lymphocytic infiltration and septal thickening of alveolar walls. In two cases with mild interstitial lung disease, the everolimus therapy was successfully continued. In four cases with Grade 3 interstitial lung disease, the drug was discontinued and steroid therapy was initiated. Pulmonary symptoms and radiological abnormalities resolved within 2 months. Serum Krebs von den Lungen 6 was elevated compared with baseline in all cases with interstitial lung disease. Some patients who developed mild interstitial lung disease during everolimus treatment could continue to receive the treatment. Even when severe interstitial lung disease developed, withdrawal of the drug and short-term use of high-dose steroids resulted in rapid recovery. Prompt recognition of interstitial lung disease exacerbation as well as exclusion of progressive disease or infection is of primary importance.

  18. 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

  19. Case of lung carcinoma revealed by vulvar metastasis associated with systemic scleroderma and literature review

    PubMed Central

    Mansouri, Safae; Glaria, Luis A.; Asmae, Naim; Flores, Luis F.

    2013-01-01

    Metastatic carcinoma to the vulva is rare, where the incidence is believed to be between 5% and 8%. However, malignant tumors have been described in 3–11% of systemic scleroderma (SSc) cases. We report the case of one patient, a 66-year-old postmenopausal woman, whose medical history was marked with rheumatic vascular disease (systemic scleroderma) since 1993 without muscular, renal, cardiac lesions or HTA (arterial hypertension) and without tobacco history. The woman presented with a new vulvar mass of the right labia in December 2011 that had progressively enlarged in size. CT scan of the abdominopelvic region demonstrated a lobular mass of the right labia with central necrosis, 7 cm on the wide axis, and the rectum and the vaginal wall were normal. No inguinal or iliac lymphadenopathy was noted. An outpatient excisional biopsy revealed a poorly differentiated malignant tumor suggestive of carcinoma. IHC: CK7+/CK20−, estrogen receptors−, AE 1 AE 3+, vimentine+, S100−, Desmina−, CD34−, KI 67: 20%. The thoracic scan revealed a large mass of 4 cm × 3 cm in the right lung base with right paratracheal lymphadenopathy 3 cm × 2 cm. A bronchoscopy revealed discrete stenosis of the mediastinal portion of the right bronchial tree. The bronchial biopsy also revealed poorly differentiated lung carcinoma, non-small cell, which was identical with the vulvar tumor. Conclusion The presence of the single lung lesion with only one lymphadenopathy paratracheal with pathological and immunohistochemical (IHC) profile similar to the vulvar lesion, and a particular IHC profile with CK7+ and CK20− was detected – that is more specific to the primitive pulmonary cancer, and the presence of only one sarcoma marker vementine+, desmine and actine−. Also the presence of KI 67: 20%, predicted the proliferative and great metastatic power of the lung tumor was observed. Additionally, lung cancer was the most frequent type and may develop in scleroderma as reported in

  20. 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.

  1. [Neuroendocrine tumors of the lungs. From small cell lung carcinoma to diffuse idiopathic pulmonary neuroendocrine cell hyperplasia].

    PubMed

    Schnabel, P A; Junker, K

    2014-11-01

    The new World Health Organization (WHO) classification announced for 2015 will for the first time present all neuroendocrine tumors (NET) of the lungs in one single section. In this classification high grade small cell lung carcinoma (SCLC) and large cell neuroendocrine carcinoma (LCNEC) will be discriminated from intermediate grade atypical carcinoid (AC) and low grade typical carcinoid as well as from the preinvasive lesion diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH). The LCNEC was previously listed under the section of large cell carcinomas. The LCNEC could previously be diagnosed according to the current WHO classification from 2004 which is designed for resection specimens. According to this the main diagnostic criteria are a neuroendocrine growth pattern which can be difficult or impossible to detect in biopsy material, non-small cell cytological features, more than 10 mitoses per 2 mm(2) (mean 70-80 per 2 mm(2)), tumor cell necrosis, and an immunohistochemical positivity for at least one neuroendocrine marker other than neuron-specific enolase (NSE). The presentation of all neuroendocrine tumors of the lungs in one section allows a more direct comparison and a better differential diagnostic discrimination of the different entities.

  2. Lymphoepithelioma-like carcinoma of the lung: an unusual case and literature review.

    PubMed

    Huang, Yuan-Chun; Hsueh, Ching; Ho, Shang-Yun; Liao, Chiung-Ying

    2013-01-01

    We described a case of lymphoepithelioma-like carcinoma (LELC) of the lung of a 65-year-old man with initial symptoms of intermittent chest pain and mild shortness of breath for 2 weeks. A right-lung mass was noted on chest computed tomography (CT) scan and was proved histopathologically as LELC of lung after video-assisted thorascopic lobectomy. He was successfully treated with lobectomy with postoperative adjuvant chemotherapy and is alive without signs of recurrence for 36 months after the diagnosis. It is important for clinicians, pathologists, and radiologists to understand the clinical, pathological, and radiological presentations of this neoplasm to avoid improper clinical decision making and misdiagnosis.

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

    PubMed Central

    2010-01-01

    Background Although human papillomavirus (HPV) genome has been detected in lung cancer, its prevalence is highly variable around the world. Higher frequencies have been reported in far-east Asian countries, when compared with European countries. The present study analysed the HPV-16 presence in 60 lung carcinomas from the Asian countries China, Pakistan and Papua New Guinea. Results HPV-16 was present in 8/59 (13%) samples. According to histological type, HPV-16 was detected in 8/18 (44%) squamous cell carcinomas (SQCs), which were mainly from Pakistan; 0/38 (0%) adenocarcinomas (ACs), which were mainly from China; and in 0/4 (0%) small cell carcinomas (SCLCs). The observed histological difference was statistically significant (p < 0.001). HPV-16 viral load was also determined using real-time polymerase chain reaction (qRT-PCR); it ranged between 411 to 2345 copies/100 ng of genomic DNA. HPV-16 genome was found integrated into the host genome in every HPV-16 positive carcinoma. Conclusion These results support the notion that HPV-16 infection is highly associated with SQCs in Pakistan. Our results show a frequent HPV-16 integration in SQCs, although the low viral load casts doubt respect a direct etiological role of HPV in lung carcinomas from Asia. Additional HPV-16 characterization is necessary to establish a direct or indirect etiological role of HPV in this malignancy. PMID:21080966

  4. A retrospective analysis of the clinicopathological characteristics of large cell carcinoma of the lung

    PubMed Central

    LIANG, RUI; CHEN, TIAN-XING; WANG, ZHI-QIANG; JIN, KE-WEI; ZHANG, LIAN-YU; YAN, QING-NA; ZHANG, HUI-HUA; WANG, WAN-PU

    2015-01-01

    The aim of the present study was to analyze and summarize the clinicopathological characteristics of large-cell lung carcinoma (LCLC) of the lung, in order to improve the definite diagnosis rate of LCLC. Clinicopathological data of 174 patients with LCLC, confirmed pathologically, were retrospectively reviewed. The 174 cases of LCLC accounted for 5.7% of the total lung cancer cases during the corresponding time period at the Affiliated Cancer Hospital of Tianjin Medical University (Tianjin, China), among which there were 131 males and 43 females with an average age of 61.4 years. The postoperative pathological diagnosis of the 174 cases showed 80 cases of classic LCLC, 64 cases of large cell neuroendocrine carcinoma (LCNEC), six cases of combined LCNEC, 19 cases of basaloid carcinoma, three cases of clear cell carcinoma and two cases of lymphoepithelioma-like carcinoma. Of the total 174 LCLC cases, 96 patients exhibited lymph node metastasis. LCLC is a highly aggressive malignancy with a high tendency of invasion and metastasis, although the incidence rate is low. A definite diagnosis of LCLC primarily relies on the pathological diagnosis. Each subtype of LCLC has its own pathomorphological and immunohistochemical characteristics. PMID:25452802

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

    USDA-ARS?s Scientific Manuscript database

    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

    USDA-ARS?s Scientific Manuscript database

    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. CIMAvax EGF vaccine for stage IIIb/IV non-small cell lung carcinoma

    PubMed Central

    Cheng, Jian Y.; Kananathan, Ratnavelu

    2012-01-01

    This case report documents the use of the CIMAvax Epidermal Growth Factor vaccine regimen in a 54 y old female with stage IIIb non-small cell lung carcinoma. Even after 48 mo since diagnosis her ECOG performance remains at zero. Further, this report documents a reaction to the vaccine of grade 3 severity not previously documented. PMID:22906936

  8. Adjuvant, specific, active immunotherapy for resectable squamous cell lung carcinoma: a 5-year survival analysis.

    PubMed

    Takita, H; Hollinshead, A C; Adler, R H; Bhayana, J; Ramundo, M; Moskowitz, R; Rao, U N; Raman, S

    1991-01-01

    In 1976 Stewart et al. (Annals of the New York Academy of Sciences 277:436-466) reported the effectiveness of adjuvant specific active immunotherapy of lung carcinoma in improving the postoperative survival of stage I lung carcinoma patients in a phase II study using lung carcinoma-associated antigen (TAA) and complete Freund's adjuvant (CFA). A phase III study was then designed by the authors to see the effects of specific active immunotherapy compared to the conventional management (no treatment) and to nonspecific immunotherapy. From 1976 to 1981, 85 patients with resectable (stages I and II) squamous cell lung carcinoma were entered into a randomized study: 1) control group; 2) specific immunotherapy group--three monthly doses of 500 micrograms of TAA emulsified with CFA; 3) nonspecific immunotherapy group--three monthly doses of CFA emulsified in saline. All the patients in the study received skin tests with 100 micrograms of the same TAA used for the immunotherapy. Recently, a 5-year follow-up of all the patients became available: The life table 5-year survival of group 1 was 34%, of group 2 was 75%, and of group 3 was 53%. The median survivals for the three groups were group 1, 38 months; group 2, 106 months; and group 3, 71 months. The difference was significant at P = .007 (Cox-Mantel test).

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

    SciTech Connect

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

    1984-12-01

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

  10. Effect of FHIT loss and p53 mutation on HPV-infected lung carcinoma development.

    PubMed

    Yu, Yan; Liu, Xiaofei; Yang, Yuxuan; Zhao, Xiaodan; Xue, Jianjun; Zhang, Weixiao; Yang, Aimin

    2015-07-01

    High-risk human papillomavirus (HPV)16/18 infection in the development of lung cancer has previously been identified, and fragile histidine triad (FHIT) loss and p53 mutation are frequently observed in the disease. However, the association between these factors has not been well studied. The present study aimed to further investigate the significance of HPV infection, FHIT loss and p53 mutations in the development of lung cancer and their possible associations. DNA was extracted from paraffin-embedded specimens from 88 cases of squamous cell carcinoma (SCC), 56 of adenocarcinoma (AC), 36 of small cell lung carcinoma (SCLC) and 110 non-cancer control cases of lung neoplasms. The prevalence of HPV infection was determined by polymerase chain reaction analysis, and FHIT loss and p53 mutations were detected by immunohistochemistry. The χ(2), Fisher's exact and Pearson correlation tests were applied for statistical analysis. The results of the present study demonstrated that HPVL1 (the major capsid protein of HPV), HPV16 and HPV18 infection were more prevalent in the lung cancer samples compared with the non-cancer controls (all P<0.001). FHIT loss occurred more frequently in the lung cancer samples (44.44%) compared with the non-cancer controls (7.25%) (P<0.001). FHIT loss in the HPVL1-positive group was significantly increased compared with the HPVL1-negative group in the lung cancer cases and the non-cancer controls (P<0.05). In the lung cancer cases, the p53 mutation rates in the HPVL1- and HPV16/18-positive groups were significantly increased compared with the HPVL1- and HPV16/18-negative groups (P<0.05). In the 180 lung cancer cases, the coexistence rate of FHIT loss and a history of smoking was 38.33% (69/180; Pearson contingency coefficient of r=0.318; P<0.001). FHIT loss and p53 mutation exhibited a synergistic effect on HPV-associated lung cancer (Pearson contingency coefficient r=0.357, P<0.001). The present study demonstrated that FHIT loss may be important

  11. 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.

  12. [The effect of sclareol lactone and sclareol glycol on artificially induced lung metastases of Lewis lung carcinoma (a preliminary report)].

    PubMed

    Astardzhieva, Z; Stoichkov, I

    1990-01-01

    The prophylactic effect of tetralabdanes, obtained by chemical decomposition of the natural diterpene sclareol (Il. Ognianov and T. Somleva) on the growth of artificially induced lung metastases was studied. After intravenous administration of 25 mg/kg of sclareol-lacton 30 minutes before the transplantation of tumorous cells of Lewis [correction of Luis] lung carcinoma the number of metastases was reduced with 37.5% but in a dose of 50 mg/kg from--33 to 63%. In a dose of 100 mg/kg of sclareol-lacton metastases were increased with 2--7%. Sclareolglycol administered in a dose of 25 mg/kg under the same experimental conditions, reduced lung metastases with 38%, but in a dose of 50 mg/kg--from 26% to 61%. Its administration in a dose of 100 mg/kg stimulated their formation with 62%.

  13. Small-cell carcinoma of the lung resembling a brachial plexus tumour.

    PubMed

    Ferreira, A J A; Peleteiro, M C; Correia, J H D; Jesus, S O; Goulão, A

    2005-06-01

    A small-cell carcinoma of the lung was identified in a six-year-old female German shepherd dog with a history of chronic lameness of the left forelimb, Horner's syndrome and sensory deficits on the caudal portion of the left forelimb below the elbow. A mass, the exact location of which was difficult to ascertain, was identified during radiographic examination of the thorax. It was easily identified, using magnetic resonance imaging, as an apical tumour of the left lung with dorsal extension and involvement of paraspinal structures, such as spinal nerve roots C8 to T1 and the sympathetic trunk. Postmortem examination confirmed a mass in the left apical lobe of the lung, compatible with a diagnosis of small-cell carcinoma by histopathology and immunohistochemistry. This clinical presentation is similar to Pancoast syndrome described in humans.

  14. 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

  15. Liposomal daunorubicin overcomes drug resistance in human breast, ovarian and lung carcinoma cells.

    PubMed

    Sadava, David; Coleman, Aaron; Kane, Susan E

    2002-11-01

    Multi-drug resistance due in part to membrane pumps such as P-glycoprotein (Pgp) is a major clinical problem in human cancers. We tested the ability of liposomally-encapsulated daunorubicin (DR) to overcome resistance to this drug. A widely used breast carcinoma cell line originally selected for resistance in doxorubicin (MCF7ADR) was 4-fold resistant to DR compared to the parent MCF7 cells (IC50 79 nM vs. 20 nM). Ovarian carcinoma cells (SKOV3) were made resistant by retroviral transduction of MDR1 cDNA and selection in vinblastine. The resulting SKOV3MGP1 cells were 130-fold resistant to DR compared to parent cells (IC50 5700 nM vs. 44 nM). Small-cell lung carcinoma cells (H69VP) originally selected for resistance to etoposide were 6-fold resistant to DR compared to H69 parent cells (IC50 180 nM vs. 30 nM). In all three cases, encapsulation of DR in liposomes as Daunoxome (Gilead) did not change the IC50 of parent cells relative to free DR. However, liposomal DR overcame resistance in MCF7ADR breast carcinoma cells (IC50 20 nM), SKOV3MGP1 ovarian carcinoma cells (IC50 237 nM) and H69VP small-cell lung carcinoma cells (IC50 27 nM). Empty liposomes did not affect the IC50 for free DR in the three resistant cell lines, nor did empty liposomes affect the IC50 for other drugs that are part of the multi-drug resistance phenotype (etoposide, vincristine) in lung carcinoma cells. These data indicate the possible value of liposomal DR in overcoming Pgp-mediated drug resistance in human cancer.

  16. Expression of urokinase-type plasminogen activator, stromelysin 1, stromelysin 3, and matrilysin genes in lung carcinomas.

    PubMed Central

    Bolon, I.; Devouassoux, M.; Robert, C.; Moro, D.; Brambilla, C.; Brambilla, E.

    1997-01-01

    We have previously shown that the extracellular-matrix-degrading enzymes, urokinase-type plasminogen activator (u-PA), stromelysin 1, stromelysin 3, and matrilysin, may play an important role in the transition from lung preneoplasia to invasive carcinoma. Using in situ hybridization and immunohistochemistry, we analyzed serial frozen sections for the expression of these enzymes in 89 lung carcinomas including 25 neuroendocrine (NE) carcinomas (10 small-cell lung carcinomas, 7 large-cell NE carcinomas, 1 atypical, and 7 typical carcinoids) and 64 non-small-cell, non-NE carcinomas (29 squamous and 7 basaloid carcinomas, 23 adenocarcinomas, and 5 large-cell carcinomas). Proteases, except matrilysin, were more often expressed in stromal than cancer cells. In non-small-cell, non-NE carcinomas, stromal co-expression of u-PA and stromelysin 3 was seen in 80 to 90% of the tumors and was highly correlated (P < 0.0001). Stromal u-PA and stromelysin 3 expression was linked to tumor size (P = 0.01 and 0.03, respectively) and lymph node involvement (P = 0.001 and 0.02, respectively). Epithelial expression of u-PA was correlated to tumor size (P = 0.04). Epithelial expression of stromelysin 3 predominated in squamous and basaloid carcinomas (P = 0.0005) and was inversely correlated to squamous differentiation (P = 0.018). Epithelial expression of matrilysin predominated in adenocarcinomas and large-cell carcinomas (P = 0.07). In NE carcinomas including small-cell lung carcinomas, stromal expression of u-PA was correlated to lymph node metastasis (P = 0.017). Epithelial expression of all enzymes were significantly less frequent in NE than in non-NE tumors. We conclude that 1) epithelial expression of matrix proteases in lung cancer is linked to cell phenotype (NE versus non-NE, squamous versus glandular) and 2) their stromal, rather than epithelial, expression influences local metastasis. Images Figure 1 PMID:9137088

  17. [Complete remission of endobronchial, parenchymal and hilar lymphatic lung metastases of prostatic carcinoma after anti-androgenic hormotherapy].

    PubMed

    Morrone, N; Volpe, V L; Dourado, A M; Coletta, E N

    1996-01-01

    A 65 year old male Negro had respiratory and urinary symptoms for the last 5 months. The work-up disclosed a prostatic carcinoma with metastases in bones, bronchus, lung parenchyma and hilar lymphnodes. Prostatic and bronchial biopsies revealed carcinoma; specific prostatic antigen was detected in both. A prostatectomy with bilateral orchiectomy was performed followed by anti-androgenic hormotherapy. Complete remission of metastatic bronchial, lung parenchyma and lymphatic lesions was observed; bone lesions did not change. lung and bronchial metastases of prostatic carcinoma may resemble primitive bronchial tumor; complete remission with anti-androgenic therapy is possible, saving the patient from unnecessary radio and/or chemotherapy.

  18. “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

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

    ClinicalTrials.gov

    2016-12-19

    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

  20. Integrative and Comparative Genomic Analysis of Lung Squamous Cell Carcinomas in East Asian Patients

    PubMed Central

    Kim, Youngwook; Hammerman, Peter S.; Kim, Jaegil; Yoon, Ji-ae; Lee, Yoomi; Sun, Jong-Mu; Wilkerson, Matthew D.; Pedamallu, Chandra Sekhar; Cibulskis, Kristian; Yoo, Yeong Kyung; Lawrence, Michael S.; Stojanov, Petar; Carter, Scott L.; McKenna, Aaron; Stewart, Chip; Sivachenko, Andrey Y.; Oh, In-Jae; Kim, Hong Kwan; Choi, Yong Soo; Kim, Kwhanmien; Shim, Young Mog; Kim, Kyu-Sik; Song, Sang-Yun; Na, Kook-Joo; Choi, Yoon-La; Hayes, D. Neil; Kim, Jhingook; Cho, Sukki; Kim, Young-Chul; Ahn, Jin Seok; Ahn, Myung-Ju; Getz, Gad; Meyerson, Matthew; Park, Keunchil

    2014-01-01

    Purpose Lung squamous cell carcinoma (SCC) is the second most prevalent type of lung cancer. Currently, no targeted therapeutics are approved for treatment of this cancer, largely because of a lack of systematic understanding of the molecular pathogenesis of the disease. To identify therapeutic targets and perform comparative analyses of lung SCC, we probed somatic genome alterations of lung SCC by using samples from Korean patients. Patients and Methods We performed whole-exome sequencing of DNA from 104 lung SCC samples from Korean patients and matched normal DNA. In addition, copy-number analysis and transcriptome analysis were conducted for a subset of these samples. Clinical association with cancer-specific somatic alterations was investigated. Results This cancer cohort is characterized by a high mutational burden with an average of 261 somatic exonic mutations per tumor and a mutational spectrum showing a signature of exposure to cigarette smoke. Seven genes demonstrated statistical enrichment for mutation: TP53, RB1, PTEN, NFE2L2, KEAP1, MLL2, and PIK3CA). Comparative analysis between Korean and North American lung SCC samples demonstrated a similar spectrum of alterations in these two populations in contrast to the differences seen in lung adenocarcinoma. We also uncovered recurrent occurrence of therapeutically actionable FGFR3-TACC3 fusion in lung SCC. Conclusion These findings provide new steps toward the identification of genomic target candidates for precision medicine in lung SCC, a disease with significant unmet medical needs. PMID:24323028

  1. Targeting FGFR in Squamous Cell Carcinoma of the Lung.

    PubMed

    Hashemi-Sadraei, Neda; Hanna, Nasser

    2017-07-06

    Unlike for adenocarcinomas of the lung, no molecular targeted therapies have yet been developed for squamous cell lung cancers, because targetable oncogenic aberrations are scarce in this tumor type. Recent discoveries have established that the fibroblast growth factor (FGF) signaling pathway plays a fundamental role in cancer development by supporting tumor angiogenesis and cancer cell proliferation via different mechanisms. Through comprehensive genomic studies, aberrations in the FGF pathway have been identified in various tumor types, including squamous cell lung cancer, making FGF receptor (FGFR) a potentially druggable target in this malignancy. Several multi-targeted tyrosine kinase inhibitors include FGFR in their target spectrum and a number of these compounds have been approved for clinical use in different cancers. Novel agents selectively targeting FGFRs have been developed and are currently under investigation in clinical trials, showing promising results. This article reviews FGFR aberrations and the clinical data involving selective and multikinase FGFR inhibitors in squamous cell lung cancer.

  2. 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

  3. Overexpression and activation of hepatocyte growth factor/scatter factor in human non-small-cell lung carcinomas.

    PubMed Central

    Olivero, M.; Rizzo, M.; Madeddu, R.; Casadio, C.; Pennacchietti, S.; Nicotra, M. R.; Prat, M.; Maggi, G.; Arena, N.; Natali, P. G.; Comoglio, P. M.; Di Renzo, M. F.

    1996-01-01

    Hepatocyte growth factor/scatter factor (HGF/SF) stimulates the invasive growth of epithelial cells via the c-MET oncogene-encoded receptor. In normal lung, both the receptor and the ligand are detected, and the latter is known to be a mitogenic and a motogenic factor for both cultured bronchial epithelial cells and non-small-cell carcinoma lines. Here, ligand and receptor expression was examined in 42 samples of primary human non-small-cell lung carcinoma of different histotype. Each carcinoma sample was compared with adjacent normal lung tissue. The Met/HGF receptor was found to be 2 to 10-fold increased in 25% of carcinoma samples (P = 0.0113). The ligand, HGF/SF, was found to be 10 to 100-fold overexpressed in carcinoma samples (P < 0.0001). Notably, while HGF/SF was occasionally detectable and found exclusively as a single-chain inactive precursor in normal tissues, it was constantly in the biologically-active heterodimeric form in carcinomas. Immunohistochemical staining showed homogeneous expression of both the receptor and the ligand in carcinoma samples, whereas staining was barely detectable in their normal counterparts. These data show that HGF/SF is overexpressed and consistently activated in non-small-cell lung carcinomas and may contribute to the invasive growth of lung cancer. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:8980383

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

    PubMed Central

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

    2014-01-01

    BAG3, member the HSP70 co-chaperones family, has been shown to play a relevant role in the survival, growth and invasiveness of different tumor types. In this study, we investigate the expression of BAG3 in 66 specimens from different lung tumors and the role of this protein in small cell lung cancer (SCLC) tumor growth. Normal lung tissue did not express BAG3 while we detected the expression of BAG3 by immunohistochemistry in all the 13 squamous cell carcinomas, 13 adenocarcinomas and 4 large cell carcinomas. Furthermore, we detected BAG3 expression in 22 of the 36 SCLCs analyzed. The role on SCLC cell survival was determined by down-regulating BAG3 levels in two human SCLC cell lines, i.e. H69 and H446, in vitro and measuring cisplatin induced apoptosis. Indeed down-regulation of BAG3 determines increased cell death and sensitizes cells to cisplatin treatment. The effect of BAG3 down-regulation on tumor growth was also investigated in an in vivo xenograft model by treating mice with an adenovirus expressing a specific bag3 siRNA. Treatment with bag3 siRNA-Ad significantly reduced tumor growth and improved animal survival. In conclusion we show that a subset of SCLCs over express BAG3 that exerts an anti-apoptotic effect resulting in resistance to chemotherapy. PMID:25149536

  5. 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.

  6. [What is the prognostic significance of histomorphology in small cell lung carcinoma?].

    PubMed

    Facilone, F; Cimmino, A; Assennato, G; Sardelli, P; Colucci, G A; Resta, L

    1993-01-01

    What is the prognostic significant of the histomorphology in the small cell carcinomas of the lung? After the WHO classification of the lung cancer (1981), several studies criticized the subdivision of the small cell carcinoma in three sub-types (oat-cell, intermediate cell and combined types). The role of histology in the prognostic predition has been devaluated. In order to verify the prognostic value of the morphology of the small cell types of lung cancer, we performed a multivariate analysis in 62 patients. The survival rate was analytically compared with the following parameters: nuclear maximum diameter, nuclear form, nuclear chromatism, chromatine distribution, presence of nucleolus, evidence of cytoplasm. The results showed that none of these parameters are able to express a prognostic value. According to the recent studies, we think that the small cell carcinoma of the lung is a neoplasia with a multiform histologic pattern. Differences observed in clinical management are not correlate with the morphology, but with other biological parameters still unknown.

  7. 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

  8. Automatic Segmentation of Lung Carcinoma Using 3D Texture Features in 18-FDG PET/CT.

    PubMed

    Markel, Daniel; Caldwell, Curtis; Alasti, Hamideh; Soliman, Hany; Ung, Yee; Lee, Justin; Sun, Alexander

    2013-01-01

    Target definition is the largest source of geometric uncertainty in radiation therapy. This is partly due to a lack of contrast between tumor and healthy soft tissue for computed tomography (CT) and due to blurriness, lower spatial resolution, and lack of a truly quantitative unit for positron emission tomography (PET). First-, second-, and higher-order statistics, Tamura, and structural features were characterized for PET and CT images of lung carcinoma and organs of the thorax. A combined decision tree (DT) with K-nearest neighbours (KNN) classifiers as nodes containing combinations of 3 features were trained and used for segmentation of the gross tumor volume. This approach was validated for 31 patients from two separate institutions and scanners. The results were compared with thresholding approaches, the fuzzy clustering method, the 3-level fuzzy locally adaptive Bayesian algorithm, the multivalued level set algorithm, and a single KNN using Hounsfield units and standard uptake value. The results showed the DTKNN classifier had the highest sensitivity of 73.9%, second highest average Dice coefficient of 0.607, and a specificity of 99.2% for classifying voxels when using a probabilistic ground truth provided by simultaneous truth and performance level estimation using contours drawn by 3 trained physicians.

  9. Automatic Segmentation of Lung Carcinoma Using 3D Texture Features in 18-FDG PET/CT

    PubMed Central

    Markel, Daniel; Caldwell, Curtis; Alasti, Hamideh; Soliman, Hany; Ung, Yee; Lee, Justin; Sun, Alexander

    2013-01-01

    Target definition is the largest source of geometric uncertainty in radiation therapy. This is partly due to a lack of contrast between tumor and healthy soft tissue for computed tomography (CT) and due to blurriness, lower spatial resolution, and lack of a truly quantitative unit for positron emission tomography (PET). First-, second-, and higher-order statistics, Tamura, and structural features were characterized for PET and CT images of lung carcinoma and organs of the thorax. A combined decision tree (DT) with K-nearest neighbours (KNN) classifiers as nodes containing combinations of 3 features were trained and used for segmentation of the gross tumor volume. This approach was validated for 31 patients from two separate institutions and scanners. The results were compared with thresholding approaches, the fuzzy clustering method, the 3-level fuzzy locally adaptive Bayesian algorithm, the multivalued level set algorithm, and a single KNN using Hounsfield units and standard uptake value. The results showed the DTKNN classifier had the highest sensitivity of 73.9%, second highest average Dice coefficient of 0.607, and a specificity of 99.2% for classifying voxels when using a probabilistic ground truth provided by simultaneous truth and performance level estimation using contours drawn by 3 trained physicians. PMID:23533750

  10. 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

  11. Late lung metastasis of a primary eccrine sweat gland carcinoma 10 years after initial surgical treatment: the first clinical documentation.

    PubMed

    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.

  12. Knockdown of Immature Colon Carcinoma Transcript 1 Inhibits Proliferation and Promotes Apoptosis of Non-Small Cell Lung Cancer Cells.

    PubMed

    Wang, Yiling; He, Jiantao; Zhang, Shenghui; Yang, Qingbo; Wang, Bo; Liu, Zhiyu; Wu, Xintian

    2016-07-13

    Non-small cell lung cancer, as the most frequent type lung cancer, has lower survival rate of 5 years, despite improvements in surgery and chemotherapy. Previous studies showed immature colon carcinoma transcript 1 is closely related to tumorigenesis of human cancer cells. In the present study, we found immature colon carcinoma transcript 1 was overexpressed in lung cancer tissues using Oncomine database mining, and the biological effect of immature colon carcinoma transcript 1 was investigated in non-small cell lung cancer cell lines 95D and A549. Lentivirus-mediated RNA interference was used to knock down immature colon carcinoma transcript 1 expression in 95D and A549 cells in vitro, and the knockdown efficiency was determined using quantitative real-time polymerase chain reaction and Western blot assay. Knockdown of immature colon carcinoma transcript 1 significantly suppressed non-small cell lung cancer cell proliferation and colony formation ability confirmed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and colony formation assay. Flow cytometry was applied to measure cell cycle arrest, and the result showed the cell cycle arrested in G2/M phase in 95D cells and arrested in G0/G1 phase in A549 cells. Furthermore, we measured the levels of cell cycle-associated proteins by Western blot analysis and found immature colon carcinoma transcript 1-mediated cell proliferation inhibition appeared due to downregulation of cell cycle activator cyclin D1 and upregulation of cell cycle inhibitor p21. In addition, immature colon carcinoma transcript 1 silencing significantly induced non-small cell lung cancer cell apoptosis by annexin V/7-amino-actinomycin D double-staining assay. All our data suggest that immature colon carcinoma transcript 1 may play an important role for non-small cell lung cancer cell proliferation and could be a potential molecular target for diagnosing and treating human non-small cell lung cancer.

  13. Radiofrequency Ablation of Non-Small-Cell Carcinoma of the Lung Under Real-Time FDG PET CT Guidance

    SciTech Connect

    Schoellnast, Helmut; Larson, Steven M.; Nehmeh, Sadek A.; Carrasquillo, Jorge A.; Thornton, Raymond H.; Solomon, Stephen B.

    2011-02-15

    Radiofrequency ablation (RFA) is a well-established method in treatment of patients with lung carcinomas who are not candidates for surgical resection. Usually computed tomographic (CT) guidance is used for the procedure, thus enabling needle placement and permitting evaluation of complications such as pneumothorax and bleeding. {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is generally used for tumor activity assessment and is therefore useful in follow-up after tumor treatment. A method that provides real-time image-based monitoring of RFA to ensure complete tumor ablation would be a valuable tool. In this report, we describe the behavior of preinjected FDG during PET CT-guided RFA of a non-small-cell lung carcinoma and discuss the value of FDG as a tool to provide intraprocedure monitor ablation. The size and the form of the activity changed during ablation. Ablation led to increase of the size and blurring and irregularity of the contour compared to pretreatment imaging. The maximal standardized uptake value decreased only slightly during the procedure. Therefore, before RFA, FDG PET can guide initial needle placement, but it does not serve as a monitoring tool to evaluate residual viable tissue during the procedure.

  14. Interstitial irradiation for unresectable carcinoma of the lung.

    PubMed

    Hilaris, B S; Martini, N; Batata, M; Beattie, E J

    1975-11-01

    From 1963 to 1971, 105 patients with histologically proved cancer of the lung were explored at Memorial Hospital and underwent interstitial implantation using encapsulated sources of radon 222 (53 patients) or iodine 125 (52 patients). These lung cancers were considered unresectable because of extension of the disease into the mediastinum with fixation or invasion of the major vessels, trachea, and esophagus or chest wall involvement. No apical lesions, which have a better prognosis, are included in this review. Sixty-nine patients had epidermoid cancer, 24 had adenocarcinoma, and the remaining 12 had various other histological types. All patients were staged according to the criteria proposed by the American Joint Committee using the TNM definitions (standing for tumor, nodes, and metastasis). Local control was obtained in 8 of 10 patients (80% with clinical Stage I and II unresectable cancers of the lung and in 44 of the 95 (46%) with clinical Stage III lung cancer. The two-year survival was 50% for Stages I and II and 7% for Stage III. Five patients have survived for five years or more. The complications, disease-free interval, local recurrences, distant metastases, and survival are presented and indications for this type of therapy outlined.

  15. Nodular amyloidosis of the lung and the breast mimicking breast carcinoma with pulmonary metastasis.

    PubMed

    Liaw, Y S; Kuo, S H; Yang, P C; Chen, C L; Luh, K T

    1995-05-01

    Nodular amyloidosis of the breast and lung is a rare condition of unknown aetiology. The disease runs a benign course, but offers a diagnostic problem due to nonspecific histological features. We describe the case of a 56 year old woman with a 5 year history of multiple nodules of both lungs and left breast, clinically mimicking breast carcinoma with pulmonary metastasis. To our knowledge, this is the first case of cytologically proven amyloidosis diagnosed by ultrasound-guided percutaneous transthoracic fine-needle aspiration of pulmonary nodules.

  16. Postmortem lung volume/body weight standards for term and preterm infants.

    PubMed

    De Paepe, Monique E; Shapiro, Svetlana; Hansen, Katrine; Gündoğan, Füsun

    2014-01-01

    Assessment of lung growth is a critical component of the perinatal autopsy. Increased lung liquid content may lead to overestimation of lung growth based on (wet) lung weight. In contrast, lung volume is not influenced by intraalveolar lung liquid. Our aim was to establish age-specific reference values for postmortem lung volume/BW in preterm and term infants. We performed a retrospective analysis of fetuses/infants (16-41 weeks' gestation) without (N = 134) or with (N = 79) risk factors for pulmonary hypoplasia. Lungs were inflated at standardized pressure and volumes determined by water immersion method. Lung volume increased 11-fold between 16 and 41 weeks' gestation, concomitant with a 16-fold increase in BW. Mean lung volume/BW remained constant at 33-34 ml/kg between 16 and 31 weeks' gestation and decreased to 23.4 ml/kg at term. Lung volume/BW of infants with severe risk factors (renal anomalies, diaphragmatic hernia) was significantly lower than age-matched standards. In this group, all fetuses/infants diagnosed as having lung hypoplasia by lung volume/BW also had lung hypoplasia LW/BW standards. However, in infants with "softer" risk factors (rupture of membranes, chromosomal anomalies), 5/26 cases diagnosed with lung hypoplasia based on lung volume/BW had normal LW/BW ratios. In these discrepant cases, lung sections showed significant inflammation and edema, likely accounting for increased wet lung weight. In conclusion, we determined age-specific lung volume/BW reference values for preterm and term infants. In selected situations assessment of lung volume/BW may represent a useful complementary tool to LW/BW for postmortem evaluation of lung size.

  17. Analyses of p53 antibodies in sera of patients with lung carcinoma define immunodominant regions in the p53 protein.

    PubMed Central

    Schlichtholz, B.; Trédaniel, J.; Lubin, R.; Zalcman, G.; Hirsch, A.; Soussi, T.

    1994-01-01

    Antibodies specific for human p53 were analysed in sera of lung cancer patients. We detected p53 antibodies in the sera of 24% (10/42) of patients with lung carcinoma. The distribution was as follows: 4/9 small-cell lung carcinomas (SCLCs), 2/18 squamous cell lung carcinomas (SCCs), 2/10 adenocarcinomas (ADCs) and 2/5 large-cell lung carcinomas (LCCs). p53 antibodies were always present at the time of diagnosis and did not appear during progression of the disease. Using an original peptide-mapping procedure, we precisely localised the p53 epitopes recognised by p53 antibodies. Immunodominant epitopes reacting with antibodies were localised in the amino and carboxy termini of the protein, similar to those found in breast carcinoma patients or in animals immunised with p53. In light of these data, we suggest that p53 antibodies occur via a self-immunisation process that is the consequence of p53 accumulation in tumour cells. p53 antibodies were also detected in two patients without detected malignant disease. One of these patients died 6 months later of lung carcinoma, suggesting that p53 antibodies may be a precocious marker of p53 alteration. Images Figure 2 PMID:7514026

  18. [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.

  19. Systemic AA amyloidosis in a patient with lung metastasis from renal cell carcinoma.

    PubMed

    Nobata, Hironobu; Suga, Norihiro; Itoh, Ayano; Miura, Naoto; Kitagawa, Wataru; Morita, Hiroyuki; Yokoi, Toyoharu; Banno, Shogo; Imai, Hirokazu

    2012-12-01

    AA amyloidosis occurs in patients with high levels of serum amyloid A protein (SAA), which is produced by liver cells in response to signals from several pro-inflammatory cytokines. Chronic inflammatory disease is a major cause of AA amyloidosis; however, malignant neoplasms are rarely reported to be associated with AA amyloidosis. We report herein a case of a solitary lung metastasis of renal cell carcinoma associated with systemic AA amyloidosis. Pathological specimens of the resected lung tumor demonstrated renal cell carcinoma, and the presence of IL-1β, IL-6, and TNF-α in the lymphocytes and plasma cells surrounding the tumor cells, and AA amyloid in the vascular area, but not in metastatic clear cells. Four weeks after surgery, serum IL-6, SAA, and CRP levels normalized. Although this case is very rare, it is full of interesting suggestions about the pathogenesis of malignancy-related systemic amyloidosis.

  20. Cryptococcosis mimicking lung carcinoma with brain metastases in an immunocompetent patient.

    PubMed

    Ang, Samantha Y L; Ng, Victor W L; Kumar, Shree Dinesh; Low, Sharon Y Y

    2017-01-01

    Cryptococcosis is a fungal infection caused by Cryptococcus spp. that enters the body via inhalation. This ubiquitous yeast has gained notoriety as an opportunistic pathogen in the immunosuppressed population. The authors report a case of a previously-well adult male presented with left-sided weakness. Imaging demonstrated a pulmonary mass and 2 contrast-enhancing intracranial lesions-all features suggestive of a primary lung carcinoma with brain metastases. However, further investigations confirmed disseminated cryptococcosis, without evidence of malignancy. The patient was successfully treated with a course of antifungals. To the authors' knowledge, this is the first reported case of dissemintated cryptococcosis in an immunocompetent adult male, simulating as primary lung carcinoma with brain metastases. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. 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

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

    PubMed Central

    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

    2012-01-01

    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

  3. Chaperonin (HSP60) and annexin-2 are candidate biomarkers for non-small cell lung carcinoma

    PubMed Central

    Ağababaoğlu, İsmail; Önen, Ahmet; Demir, Ayşe Banu; Aktaş, Safiye; Altun, Zekiye; Ersöz, Hasan; Şanlı, Aydın; Özdemir, Nezih; Akkoçlu, Atila

    2017-01-01

    Abstract Background: Lung cancer is responsible of 12.4% and 17.6% of all newly diagnosed cancer cases and mortality due to cancer, respectively, and 5-year survival rate despite all improved treatment options is 15%. This survival rate reaches 66% in the Stage 1 and surgically treated patients. Early diagnosis which could not be definitely and commonly achieved yet is extremely critical in obtaining high survival rate in this disease. For this reason; proteomic differences were evaluated using matrix assisted laser desorption ionization (MALDI) mass spectrometry in the subgroups of lung adenocarcinoma and squamous cell carcinoma. Methods: Fresh tissue samples of 36 malignant cases involving 83.3% (n = 30) men and 16.7% (n = 6) women patients were distributed into 2 groups as early and end stage lung cancer and each group were composed of subgroups including 18 squamous cell carcinoma (9 early stage cases, 9 end stage cases) and 18 adenocarcinoma cases (9 early stage cases, 9 end stage cases). The fresh tissues obtained from the tumoral and matched normal sites after surgical intervention. The differences in protein expression levels were determined by comparing proteomic changes in each patient. Results: In the subgroups of advanced stage adenocarcinoma; tumoral tissue revealed differences in expression of 2 proteins compared with normal parenchymal tissue. Of those; difference in protein expression in heat shock protein 60 (HSP60) was found statistically significant (P = 0.0001). Subgroups of early and advanced stage squamos cell carcinoma have differed in certain 20 protein expression of normal tissue and diseased squamos cell carcinoma. Of those, increased protein expression level of only annexin-2 protein was found statistically significant (P = 0.002). No significant difference was detected in early and advanced stage protein expressions of the tumoral tissues in the subgroups of adenocarcinoma and squamous cell carcinoma. Conclusions: We

  4. Best immunohistochemical panel in distinguishing adenocarcinoma from squamous cell carcinoma of lung: tissue microarray assay in resected lung cancer specimens.

    PubMed

    Kim, Mi Jin; Shin, Hyeong Chan; Shin, Kyeong Cheol; Ro, Jae Y

    2013-02-01

    The emergence of the targeted therapies for non-small cell lung carcinoma (NSCLC) has generated a need for accurate histologic subtyping of NSCLC. In this study, we assessed the utility of immunohistochemical markers that could be helpful in distinction between adenocarcinoma (ADC) and squamous cell carcinoma (SCC). We performed a battery of immunohistochemistry using tissue microarray for napsin-A, Thyroid transcription factor 1 (TTF-1), p63, cytokeratin (CK) 5/6, thrombomodulin (CD141), Epithelial-related antigen (MOC-31), carcinoembryonic antigen (CEA), Cyclooxygenase 2 (COX-2), high-molecular-weight CK (HMWCK), p27kip1 (p27), and Rb protein in 129 resected primary NSCLC with 81 ADCs and 48 SCCs and 10 metastatic ADC to the lung (primary in colon, 7 cases; stomach, 2 cases; vagina, 1 case). Cases of ADC and SCC were morphologically unequivocal and solid tumors with no definite squamous or glandular differentiation were excluded for this analysis. Napsin-A and TTF-1 were positive in 81% and 70% of ADC and in 0% and 2% of SCC, respectively, whereas P63 and CK5/6 were positive in 91% and 90% of SCC and in 9% and 4% of ADC, respectively (P < .001). CD141 stained significantly higher in SCC over ADC (positive in 2% of ADC and 46% of SCC. MOC-31, CEA, COX-2, HMWCK, p27, and Rb appeared to be not useful markers in distinction between ADC and SCC because of their low specificity. None of metastatic ADC to the lung showed positive for napsin-A and TTF-1. It was evident that combination of napsin-A, TTF-1, CK5/6, and p63 was the best immunohistochemical panel in differentiating ADC from SCC of the lung in this study. CD141 appeared to be a potential new marker for SCC with high specificity. Cyclooxygenase 2, MOC-31, CEA, HMWCK, p27, and Rb showed less specificity for differentiation ADC from SCC.

  5. Positive nuclear BAP1 immunostaining helps differentiate non-small cell lung carcinomas from malignant mesothelioma

    PubMed Central

    Carbone, Michele; Shimizu, David; Napolitano, Andrea; Tanji, Mika; Pass, Harvey I.; Yang, Haining; Pastorino, Sandra

    2016-01-01

    The differential diagnosis between pleural malignant mesothelioma (MM) and lung cancer is often challenging. Immunohistochemical (IHC) stains used to distinguish these malignancies include markers that are most often positive in MM and less frequently positive in carcinomas, and vice versa. However, in about 10–20% of the cases, the IHC results can be confusing and inconclusive, and novel markers are sought to increase the diagnostic accuracy. We stained 45 non-small cell lung cancer samples (32 adenocarcinomas and 13 squamous cell carcinomas) with a monoclonal antibody for BRCA1-associated protein 1 (BAP1) and also with an IHC panel we routinely use to help differentiate MM from carcinomas, which include, calretinin, Wilms Tumor 1, cytokeratin 5, podoplanin D2-40, pankeratin CAM5.2, thyroid transcription factor 1, Napsin-A, and p63. Nuclear BAP1 expression was also analyzed in 35 MM biopsies. All 45 non-small cell lung cancer biopsies stained positive for nuclear BAP1, whereas 22/35 (63%) MM biopsies lacked nuclear BAP1 staining, consistent with previous data. Lack of BAP1 nuclear staining was associated with MM (two-tailed Fisher's Exact Test, P = 5.4 × 10−11). Focal BAP1 staining was observed in a subset of samples, suggesting polyclonality. Diagnostic accuracy of other classical IHC markers was in agreement with previous studies. Our study indicated that absence of nuclear BAP1 stain helps differentiate MM from lung carcinomas. We suggest that BAP1 staining should be added to the IHC panel that is currently used to distinguish these malignancies. PMID:27447750

  6. Positive nuclear BAP1 immunostaining helps differentiate non-small cell lung carcinomas from malignant mesothelioma.

    PubMed

    Carbone, Michele; Shimizu, David; Napolitano, Andrea; Tanji, Mika; Pass, Harvey I; Yang, Haining; Pastorino, Sandra

    2016-09-13

    The differential diagnosis between pleural malignant mesothelioma (MM) and lung cancer is often challenging. Immunohistochemical (IHC) stains used to distinguish these malignancies include markers that are most often positive in MM and less frequently positive in carcinomas, and vice versa. However, in about 10-20% of the cases, the IHC results can be confusing and inconclusive, and novel markers are sought to increase the diagnostic accuracy.We stained 45 non-small cell lung cancer samples (32 adenocarcinomas and 13 squamous cell carcinomas) with a monoclonal antibody for BRCA1-associated protein 1 (BAP1) and also with an IHC panel we routinely use to help differentiate MM from carcinomas, which include, calretinin, Wilms Tumor 1, cytokeratin 5, podoplanin D2-40, pankeratin CAM5.2, thyroid transcription factor 1, Napsin-A, and p63. Nuclear BAP1 expression was also analyzed in 35 MM biopsies. All 45 non-small cell lung cancer biopsies stained positive for nuclear BAP1, whereas 22/35 (63%) MM biopsies lacked nuclear BAP1 staining, consistent with previous data. Lack of BAP1 nuclear staining was associated with MM (two-tailed Fisher's Exact Test, P = 5.4 x 10-11). Focal BAP1 staining was observed in a subset of samples, suggesting polyclonality. Diagnostic accuracy of other classical IHC markers was in agreement with previous studies. Our study indicated that absence of nuclear BAP1 stain helps differentiate MM from lung carcinomas. We suggest that BAP1 staining should be added to the IHC panel that is currently used to distinguish these malignancies.

  7. 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.

  8. Anti-tumor effect of cactus polysaccharides on lung squamous carcinoma cells (SK-MES-1).

    PubMed

    Li, W; Wu, D; Wei, B; Wang, S; Sun, Hx; Li, Xl; Zhang, F; Zhang, Cl; Xin, Y

    2014-01-01

    Cactus polysaccharides are the active components of Opuntia dillenii which have been used extensively in folk medicine. In this study, we investigate the anti-tumor effect of cactus polysaccharides on lung squamous carcinoma cells SK-MES-1. The inhibitory effect of Cactus polysaccharides on lung squamous carcinoma cells were detected by MTT assay. Cell cycle was determined by flow cytometry and cell apoptosis was determined by AnnexinV assay. Western-blotting was applied to detect P53 and PTEN protein expression in the cells treated with cactus polysaccharides. Results showed that different concentrations of wild cactus polysaccharides prevent SK-MES-1 cells growth and induces S phase arrest. The data also revealed that cactus polysaccharides cause apoptosis in SK-MES-1 cells determined by Annexin-V assay. Furthermore, cactus polysaccharides induced growth arrest and apoptosis may be due to the increase of P53 and phosphatase and tension homolog deleted on chromosome ten (PTEN) protein. Cactus polysaccharides have anti-tumor activity on lung squamous carcinoma cells.

  9. MORTALITY OF COAL-MINERS FROM CARCINOMA OF THE LUNG

    PubMed Central

    Goldman, K. P.

    1965-01-01

    The results are presented from an investigation into the mortality of miners and ex-miners employed by the National Coal Board, from a comprehensive survey of respiratory disease in a Welsh mining community, and from a study of the comparative mortality from lung cancer in Welsh mining and non-mining towns. These results, together with previously published data which have been reviewed, show that in Great Britain the death rate of coal-miners from cancer of the lung is appreciably lower than the national rate for men of comparable age. This occupational trend is not explicable by any of the factors which are known to influence the prevalence of the disease in the general population. In particular there is much evidence that the cigarette consumption of miners at least equals that of men in other occupations. The exclusion of this and other recognized aetiological factors suggests that the reduced mortality of miners from this disease is a specific effect of their occupation. This effect might be a consequence of the inhalation of coal-dust, for there is some evidence that the incidence of death from lung cancer is lowest among miners whose exposure to coal-dust has been greatest. PMID:14261709

  10. 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

  11. Tissue inhibitors of matrix metalloproteinases 1 and 2 and matrix metalloproteinase activity in the serum and lungs of mice with lewis lung carcinoma.

    PubMed

    Kisarova, Ya A; Korolenko, T A

    2012-10-01

    We studied the content of tissue inhibitors of matrix metalloproteinases 1 and 2 (TIMP-1 and TIMP-2) and activities of matrix metalloproteinases (MMP) in the serum and lungs of mice with Lewis lung carcinoma metastasizing into the lung. Metastasizing was associated with increased serum content of TIMP-1 and TIMP-2 (only on day 20 at the terminal stage of the tumor process). These data confirm the hypothesis on pro-tumorigenic role of TIMP-1 in the serum. Locally, the development of metastases was associated with a decrease in TIPM-1 concentration (day 7), an increase in TIMP-2 concentration (days 7 and 20), and elevated activity of MMP at all terms of the study (days 7, 15, and 20). Increased concentration of TIMP-2 in the lungs (but not in the serum) can be regarded as an indicator of Lewis lung carcinoma metastasizing.

  12. Developing Novel Therapeutic Approaches in Small Cell Lung Carcinoma Using Genetically Engineered Mouse Models and Human Circulating Tumor Cells

    DTIC Science & Technology

    2015-10-01

    Using Genetically Engineered Mouse Models and Human Circulating Tumor Cells PRINCIPAL INVESTIGATOR: Jeffrey Engelman MD PhD CONTRACTING...SUBTITLE Developiing Novel Therapeutic Approaches in Small Cell Lung 5a. CONTRACT NUMBER Carcinoma Using Genetically Engineered Mouse Models and 5b...biomarkers. 15. SUBJECT TERMS Small cell lung cancer (SCLC), Genetically engineered mouse model (GEMM), BH3 mimetic, TORC inhibitor, Apoptosis

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

    USDA-ARS?s Scientific Manuscript database

    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...

  14. Basaloid large cell lung carcinoma presenting as cutaneous metastasis at the colostomy site after abdominoperineal resection for rectal carcinoma.

    PubMed

    Sabater-Marco, Vicente; García-García, José Angel; Roig-Vila, José Vicente

    2013-08-01

    The occurrence of a tumor at the colostomy site after abdominoperineal resection for rectal carcinoma is rare and it may be related to a previously resected carcinoma or another primary tumor. We report a 61-year-old man who developed an ulcerated skin nodule at her colostomy site 6 years after resection of a rectal adenocarcinoma. Histopathologically, the skin nodule was composed of atypical large and pleomorphic cells with high mitotic rate and they were arranged in nests and within lymphatic channels in the dermis. The neoplastic cells were immunoreactive for cytokeratin (CK) AE1/3, CK7, CK34ßE12, epithelial membrane antigen and vimentin while detection of human papillomavirus and Epstein-Barr virus DNA was negative. A diagnosis of basaloid large cell carcinoma of pulmonary origin was suggested and it was confirmed by computed tomography-guided fine needle aspiration of a right subpleural mass. A metastatic tumor at the colostomy site is an exceptional finding and may be the first manifestation of lung cancer, especially if it consist of pleomorphic large cells with high mitotic rate and basaloid immunophenotype.

  15. Immunotherapy in urothelial carcinoma: fade or future standard?

    PubMed Central

    Breyer, Johannes; Burger, Maximilian

    2016-01-01

    Immunotherapy of non-muscle-invasive bladder carcinoma by Bacillus-Calmette-Guérin (BCG) instillation is a well-established treatment option since decades. Despite this fact, the immunocellular basis was first studied in recent years. New aspects of immunotherapy, also for progressed bladder carcinoma, might follow promising research on immunological targets. PMID:27785423

  16. 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

  17. Spinal Cord Ischemia Secondary to Epidural Metastasis from Small Cell Lung Carcinoma

    PubMed Central

    Yasui, Hirotoshi; Ozawa, Naoya; Mikami, Satoshi; Shimizu, Kenji; Hatta, Takahiro; Makino, Nami; Fukushima, Mayu; Baba, Satoshi; Makino, Yasushi

    2017-01-01

    Patient: Male, 56 Final Diagnosis: Small cell lung carcinoma Symptoms: Back pain • paralysis Medication: — Clinical Procedure: MRI Specialty: Pulmonology Objective: Unusual clinical course Background: Spinal cord ischemia is an uncommon event that is mainly caused by dissociation of the ascending aorta as a complication after aortic surgery. Spinal arteries can develop collateral circulation; therefore, the frequency of spinal infarction is about 1% of that in the brain. Few cases of spinal cord ischemia developing in the course of lung cancer have been reported. Case Report: We presented the case of a 56-year-old man with small cell lung carcinoma, cT4N2M1a (stage IV). He was treated with irradiation and 2 courses of platinum and etoposide combination chemotherapy. He complained of back pain followed by quadriplegia and sensory disturbance after cessation of chemotherapy. With a diagnosis of spinal cord metastasis, steroids were administered. However, diaphragmatic paralysis appeared a few hours later. He was started on palliative care and died after 6 days. Autopsy showed epidural metastasis and spinal ischemia at the C5 level. Conclusions: Epidural metastasis can compress the spinal artery and cause circulatory disorders. Spinal cord ischemia should be considered in patients with rapid paralysis in the course of lung cancer. PMID:28302996

  18. Antitumor Effects of JAK3 Inhibitor on the Model of Transplantable Lewis Lung Carcinoma and Mechanisms of Their Development.

    PubMed

    Zyuz'kov, G N; Amosova, E N; Chaikovskii, A V; Miroshnichenko, L A; Udut, E V; Rybalkina, O Yu; Zhdanov, V V; Udut, V V; Dygai, A M; Zueva, E P

    2016-07-01

    Mice with Lewis lung carcinoma were used to study the antitumor and antimetastatic effects of JAK3 inhibitor. The study revealed no effect of JAK3 inhibitor on the growth of primary tumor node, but found a pronounced inhibition of hematogenous spread of the pathologic process into the lungs. In vitro blockade of JAK3 in cultured Lewis lung carcinoma produced no effect on the count of the stem tumor cells and stimulated functions of committed elements. In addition, blockade of JAK3 significantly elevated maturation index of the tumor tissue.

  19. 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

  20. [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.

  1. Neutrophil Chemokines Secreted by Tumor Cells Mount a Lung Antimetastatic Response during Renal Cell Carcinoma Progression

    PubMed Central

    López-Lago, Miguel A.; Posner, Shai; Thodima, Venkata J.; Molina, Ana M.; Motzer, Robert J.; Chaganti, RSK

    2012-01-01

    The mechanism by which renal cell carcinoma (RCC) colonizes the lung microenvironment during metastasis remains largely unknown. To investigate this process, we grafted human RCC cells with varying lung metastatic potential in mice. Gene expression profiling of the mouse lung stromal compartment revealed a signature enriched for neutrophil-specific functions that was induced preferentially by poorly metastatic cells. Analysis of the gene expression signatures of tumor cell lines showed an inverse correlation between metastatic activity and the levels of a number of chemokines, including CXCL5 and IL8. Enforced depletion of CXCL5 and IL8 in these cell lines enabled us to establish a functional link between lung neutrophil infiltration, secretion of chemokines by cancer cells, and metastatic activity. We further show that human neutrophils display a higher cytotoxic activity against poorly metastatic cells compared to highly metastatic cells. Together, these results support a model in which neutrophils recruited to the lung by tumor-secreted chemokines build an antimetastatic barrier with loss of neutrophil chemokines in tumor cells acting as a critical rate-limiting step during lung metastatic seeding. PMID:22665059

  2. The distinct metabolic phenotype of lung squamous cell carcinoma defines selective vulnerability to glycolytic inhibition.

    PubMed

    Goodwin, Justin; Neugent, Michael L; Lee, Shin Yup; Choe, Joshua H; Choi, Hyunsung; Jenkins, Dana M R; Ruthenborg, Robin J; Robinson, Maddox W; Jeong, Ji Yun; Wake, Masaki; Abe, Hajime; Takeda, Norihiko; Endo, Hiroko; Inoue, Masahiro; Xuan, Zhenyu; Yoo, Hyuntae; Chen, Min; Ahn, Jung-Mo; Minna, John D; Helke, Kristi L; Singh, Pankaj K; Shackelford, David B; Kim, Jung-Whan

    2017-05-26

    Adenocarcinoma (ADC) and squamous cell carcinoma (SqCC) are the two predominant subtypes of non-small cell lung cancer (NSCLC) and are distinct in their histological, molecular and clinical presentation. However, metabolic signatures specific to individual NSCLC subtypes remain unknown. Here, we perform an integrative analysis of human NSCLC tumour samples, patient-derived xenografts, murine model of NSCLC, NSCLC cell lines and The Cancer Genome Atlas (TCGA) and reveal a markedly elevated expression of the GLUT1 glucose transporter in lung SqCC, which augments glucose uptake and glycolytic flux. We show that a critical reliance on glycolysis renders lung SqCC vulnerable to glycolytic inhibition, while lung ADC exhibits significant glucose independence. Clinically, elevated GLUT1-mediated glycolysis in lung SqCC strongly correlates with high (18)F-FDG uptake and poor prognosis. This previously undescribed metabolic heterogeneity of NSCLC subtypes implicates significant potential for the development of diagnostic, prognostic and targeted therapeutic strategies for lung SqCC, a cancer for which existing therapeutic options are clinically insufficient.

  3. Breast metastasis and lung large-cell neuroendocrine carcinoma: first clinical observation.

    PubMed

    Papa, Anselmo; Rossi, Luigi; Verrico, Monica; Di Cristofano, Claudio; Moretti, Valentina; Strudel, Martina; Zoratto, Federica; Minozzi, Marina; Tomao, Silverio

    2017-09-01

    The lung large-cell neuroendocrine carcinoma (LCNEC) is a very rare aggressive neuroendocrine tumor with a high propensity to metastasize and very poor prognosis. We report an atypical presentation of lung LCNEC was diagnosed from a metastatic nodule on the breast. Our patient is a 59-years-old woman that presented in March 2014 nonproductive cough. A CT scan showed multiple brain, lung, adrenal gland and liver secondary lesions; moreover, it revealed a breast right nodule near the chest measuring 1.8 cm. The breast nodule and lung lesions were biopsied and their histology and molecular diagnosis were LCNEC of the lung. To our knowledge, this is the first documented case of breast metastasis from LCNEC of the lung. Furthermore, breast metastasis from extramammary malignancy is uncommon and its diagnosis is difficult but important for proper management and prediction of prognosis. Therefore, a careful clinical history with a thorough clinical examination is needed to make the correct diagnosis. Moreover, metastasis to the breast should be considered in any patient with a known primary malignant tumor history who presents with a breast lump. Anyhow, pathological examination should be performed to differentiate the primary breast cancer from metastatic tumor. Therefore, an accurate diagnosis of breast metastases may not only avoid unnecessary breast resection, more importantly it is crucial to determine an appropriate and systemic treatment. © 2015 John Wiley & Sons Ltd.

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

    DOE PAGES

    Leng, Shuguang; Thomas, Cynthia L.; Snider, Amanda M.; ...

    2015-09-15

    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 usingmore » 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. Lastly, the associations are strongly supported by the functional relevance that the IL6 promoter SNP affects basal expression and carcinogen-induced IL-6 secretion« less

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

    SciTech Connect

    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.

    2015-09-15

    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. Lastly, the associations are strongly supported by the functional relevance that the IL6 promoter SNP affects basal expression and carcinogen-induced IL-6 secretion

  6. Bioluminescence-Based High-Throughput Screen Identifies Pharmacological Agents That Target Neurotransmitter Signaling in Small Cell Lung Carcinoma

    PubMed Central

    Improgo, Ma. Reina D.; Johnson, Christopher W.; Tapper, Andrew R.; Gardner, Paul D.

    2011-01-01

    Background Frontline treatment of small cell lung carcinoma (SCLC) relies heavily on chemotherapeutic agents and radiation therapy. Though SCLC patients respond well to initial cycles of chemotherapy, they eventually develop resistance. Identification of novel therapies against SCLC is therefore imperative. Methods and Findings We have designed a bioluminescence-based cell viability assay for high-throughput screening of anti-SCLC agents. The assay was first validated via standard pharmacological agents and RNA interference using two human SCLC cell lines. We then utilized the assay in a high-throughput screen using the LOPAC1280 compound library. The screening identified several drugs that target classic cancer signaling pathways as well as neuroendocrine markers in SCLC. In particular, perturbation of dopaminergic and serotonergic signaling inhibits SCLC cell viability. Conclusions The convergence of our pharmacological data with key SCLC pathway components reiterates the importance of neurotransmitter signaling in SCLC etiology and points to possible leads for drug development. PMID:21931655

  7. 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

  8. Identification of Key Transcription Factors Associated with Lung Squamous Cell Carcinoma

    PubMed Central

    Zhang, Feng; Chen, Xia; Wei, Ke; Liu, Daoming; Xu, Xiaodong; Zhang, Xing; Shi, Hong

    2017-01-01

    Background Lung squamous cell carcinoma (lung SCC) is a common type of lung cancer, but its mechanism of pathogenesis is unclear. The aim of this study was to identify key transcription factors in lung SCC and elucidate its mechanism. Material/Methods Six published microarray datasets of lung SCC were downloaded from Gene Expression Omnibus (GEO) for integrated bioinformatics analysis. Significance analysis of microarrays was used to identify differentially expressed genes (DEGs) between lung SCC and normal controls. The biological functions and signaling pathways of DEGs were mapped in the Gene Otology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database, respectively. A transcription factor gene regulatory network was used to obtain insights into the functions of DEGs. Results A total of 1,011 genes, including 539 upregulated genes and 462 downregulated genes, were filtered as DEGs between lung SCC and normal controls. DEGs were significantly enriched in cell cycle, DNA replication, p53 signaling pathway, pathways in cancer, adherens junction, and cell adhesion molecules signaling pathways. There were 57 transcription factors identified, which were used to construct a regulatory network. The network consisted of 736 interactions between 49 transcription factors and 486 DEGs. NFIC, BRCA1, and NFATC2 were the top 3 transcription factors that had the highest connectivity with DEGs and that regulated 83, 82, and 75 DEGs in the network, respectively. Conclusions NFIC, BRCA1, and NFATC2 might be the key transcription factors in the development of lung SCC by regulating the genes involved in cell cycle and DNA replication pathways. PMID:28081052

  9. 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

  10. Human papillomavirus-16 is integrated in lung carcinomas: a study in Chile

    PubMed Central

    Aguayo, F; Castillo, A; Koriyama, C; Higashi, M; Itoh, T; Capetillo, M; Shuyama, K; Corvalan, A; Eizuru, Y; Akiba, S

    2007-01-01

    The human papillomavirus (HPV) was detected in 20 (29%) out of 69 lung carcinomas (LCs) in Chile, by PCR and Southern blot, and was more frequently detected in squamous cell carcinoma (SQC) than in adenocarcinomas (46 vs 9%, P=0.001). HPV-16, positive in 11 cases, was the most frequently detected HPV genotype determined by DNA sequencing. HPV-16 E2/E6 ratio, estimated from real-time PCR analysis, was much lower than the unity, suggesting that at least a partial HPV-16 genome was integrated in all but one HPV-16-positive SQCs. The remaining one case was suspected to have only episomal HPV-16. Although the viral load was low in most of the LCs, a case showed the HPV-16 copy number as high as 8479 per nanogram DNA, which was even a few times higher than the minimum viral load of seven cervical carcinomas (observed viral load: 3356–609 392 per nanogram DNA). The expression of the HPV-16/18 E6 protein was found in only two HPV-16-positive SQCs (13%) but not in the case with the highest viral load. Although the viral load was in general very low and HPV E6 expression is none or weak, further studies seem warranted to examine aetiological involvement of high-risk HPV in lung carcinogenesis. PMID:17579626

  11. Epidermal Growth Factor Receptor Inhibition in the Management of Squamous Cell Carcinoma of the Lung

    PubMed Central

    Spaans, Johanna N.

    2016-01-01

    Molecular therapies targeting epidermal growth factor receptor (EGFR) have had a profound impact on the management of advanced non-small cell lung cancer (NSCLC). EGFR inhibition with EGFR tyrosine kinase inhibitors (EGFR-TKIs) and anti-EGFR monoclonal antibodies (mAbs) in squamous NSCLC (sqNSCLC) remains controversial in patients whose tumors are not known to harbor EGFR mutations. Recent meta-analyses of EGFR-inhibition randomized trials that are adequately powered for histological subgroup analysis and anti-EGFR trials limited to patients with squamous histology afford the opportunity to revisit EGFR treatment in sqNSCLC. In unselected patients with sqNSCLC who are not eligible for chemotherapy, EGFR-TKI therapy is a valid treatment option over placebo or best supportive care, with improved progression-free survival noted in randomized controlled trials in both the first- and second-line setting and improved overall survival (OS) in the second-line setting. In patients eligible for chemotherapy, first-line combination regimens with anti-EGFR mAbs have been shown to improve OS over chemotherapy alone in patients with squamous histology in meta-analysis and more recently in the SQUIRE sqNSCLC trial (chemotherapy with and without necitumumab). In sqNSCLC patients who respond to induction chemotherapy, maintenance therapy with erlotinib delays disease progression and may improve the survival of patients with stable disease. In the second-line setting, survival outcomes are comparable between chemotherapy and EGFR-TKIs in meta-analysis, with the latter being more tolerable as a second-line therapy. Newer-generation EGFR-TKI therapies may further benefit patients with sqNSCLC who have failed first-line chemotherapy, given the positive trial results from LUX-Lung 8 (afatinib vs. erlotinib). EGFR is a valid therapeutic target in unselected/EGFR wild-type patients with squamous cell carcinoma of the lung. With the recent approval of immune checkpoint inhibitors in the

  12. The Mayo Lung Project for early detection and localization of bronchogenic carcinoma: a status report.

    PubMed

    Fontana, R S; Sanderson, D R; Woolner, L B; Miller, W E; Bernatz, P E; Payne, W S; Taylor, W F

    1975-05-01

    The Mayo Lung Project (MLP) is a screening program designed to detect bronchogenic carcinoma at a curable stage. Screening tests include chest roentgenograms, three-day "pooled" sputum cytology studies, and lung-health questionnaires. These are being applied every four months to a study population of outpatients who have a high probability of developing lung cancer. Initial patient acceptance of the screening program has been excellent. Small asymptomatic lung cancers have been detected both roentgenographically and cytologically. The two procedures have complemented each other with little overlap. Chest roentgenography has proved most useful in diagnosing peripherally situated cancers, whereas sputum cytology studies have been most effective in identifying early squamous cancer involving major airways. At present, more cancers have been detected roentgenographically than cytologically, but the cytologically detected cases appear to have a better prognosis. Roentgenographically occult cancers have been localized with regularity, although the localization process is complicated. Theoretically, vigorous application of radiologic and cytologic screening, combined with optimum use of localizing procedures and treatment, could increase the five-year survival rate among lung cancer patients to nearly 50 percent. However, the actual survivorship attained will ultimately be determined by currently imponderable factors such as patient acceptance of longterm screening, frequency of multicentric respiratory cancers, and incidence of noncancerous smoking-related diseases, especially chronic obstructive pulmonary disease and ischemic heart disease.

  13. Inhibitory effects of docosahexaenoic acid on colon carcinoma 26 metastasis to the lung.

    PubMed Central

    Iigo, M.; Nakagawa, T.; Ishikawa, C.; Iwahori, Y.; Asamoto, M.; Yazawa, K.; Araki, E.; Tsuda, H.

    1997-01-01

    Unsaturated fatty acids, including n-3 polyunsaturated fatty acids (PUFAs) such as docosahexaenoic acid (C22:6, DHA) and eicosapentaenoic acid (C20:5, EPA), and a series of n-6 PUFAs were investigated for their anti-tumour and antimetastatic effects in a subcutaneous (s.c.) implanted highly metastatic colon carcinoma 26 (Co 26Lu) model. EPA and DHA exerted significant inhibitory effects on tumour growth at the implantation site and significantly decreased the numbers of lung metastatic nodules. Oleic acid also significantly inhibited lung metastatic nodules. Treatment with arachidonic acid showed a tendency for reduction in colonization. However, treatment with high doses of fatty acids, especially linoleic acid, increased the numbers of lung metastatic nodules. DHA and EPA only inhibited lung colonizations when administered together with the tumour cells, suggesting that their incorporation is necessary for an influence to be exerted. Chromatography confirmed that contents of fatty acids in both tumour tissues and plasma were indeed affected by the treatments. Tumour cells pretreated with fatty acids in vivo, in particular DHA, also showed a low potential for lung colony formation when transferred to new hosts. Thus, DHA treatment exerted marked antimetastatic activity associated with pronounced change in the fatty acid component of tumour cells. The results indicate that uptake of DHA into tumour cells results in altered tumour cell membrane characteristics and a decreased ability to metastasize. PMID:9043019

  14. 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

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

    PubMed Central

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

    1988-01-01

    It has been hypothesized that bombesin-like peptides produced by small cell lung carcinomas may sustain deregulated proliferation through an autocrine mechanism. We 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. We 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 Mn2+. 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. Images PMID:2451242

  16. Heterotypic paracrine signaling drives fibroblast senescence and tumor progression of large cell carcinoma of the lung

    PubMed Central

    Lugo, Roberto; Gabasa, Marta; Andriani, Francesca; Puig, Marta; Facchinetti, Federica; Ramírez, Josep; Gómez-Caro, Abel; Pastorino, Ugo; Fuster, Gemma; Almendros, Isaac; Gascón, Pere; Davalos, Albert; Reguart, Noemí; Roz, Luca; Alcaraz, Jordi

    2016-01-01

    Senescence in cancer cells acts as a tumor suppressor, whereas in fibroblasts enhances tumor growth. Senescence has been reported in tumor associated fibroblasts (TAFs) from a growing list of cancer subtypes. However, the presence of senescent TAFs in lung cancer remains undefined. We examined senescence in TAFs from primary lung cancer and paired control fibroblasts from unaffected tissue in three major histologic subtypes: adenocarcinoma (ADC), squamous cell carcinoma (SCC) and large cell carcinoma (LCC). Three independent senescence markers (senescence-associated beta-galactosidase, permanent growth arrest and spreading) were consistently observed in cultured LCC-TAFs only, revealing a selective premature senescence. Intriguingly, SCC-TAFs exhibited a poor growth response in the absence of senescence markers, indicating a dysfunctional phenotype rather than senescence. Co-culturing normal fibroblasts with LCC (but not ADC or SCC) cancer cells was sufficient to render fibroblasts senescent through oxidative stress, indicating that senescence in LCC-TAFs is driven by heterotypic signaling. In addition, senescent fibroblasts provided selective growth and invasive advantages to LCC cells in culture compared to normal fibroblasts. Likewise, senescent fibroblasts enhanced tumor growth and lung dissemination of tumor cells when co-injected with LCC cells in nude mice beyond the effects induced by control fibroblasts. These results define the subtype-specific aberrant phenotypes of lung TAFs, thereby challenging the common assumption that lung TAFs are a heterogeneous myofibroblast-like cell population regardless of their subtype. Importantly, because LCC often distinguishes itself in the clinic by its aggressive nature, we argue that senescent TAFs may contribute to the selective aggressive behavior of LCC tumors. PMID:27384989

  17. Heterotypic paracrine signaling drives fibroblast senescence and tumor progression of large cell carcinoma of the lung.

    PubMed

    Lugo, Roberto; Gabasa, Marta; Andriani, Francesca; Puig, Marta; Facchinetti, Federica; Ramírez, Josep; Gómez-Caro, Abel; Pastorino, Ugo; Fuster, Gemma; Almendros, Isaac; Gascón, Pere; Davalos, Albert; Reguart, Noemí; Roz, Luca; Alcaraz, Jordi

    2016-12-13

    Senescence in cancer cells acts as a tumor suppressor, whereas in fibroblasts enhances tumor growth. Senescence has been reported in tumor associated fibroblasts (TAFs) from a growing list of cancer subtypes. However, the presence of senescent TAFs in lung cancer remains undefined. We examined senescence in TAFs from primary lung cancer and paired control fibroblasts from unaffected tissue in three major histologic subtypes: adenocarcinoma (ADC), squamous cell carcinoma (SCC) and large cell carcinoma (LCC). Three independent senescence markers (senescence-associated beta-galactosidase, permanent growth arrest and spreading) were consistently observed in cultured LCC-TAFs only, revealing a selective premature senescence. Intriguingly, SCC-TAFs exhibited a poor growth response in the absence of senescence markers, indicating a dysfunctional phenotype rather than senescence. Co-culturing normal fibroblasts with LCC (but not ADC or SCC) cancer cells was sufficient to render fibroblasts senescent through oxidative stress, indicating that senescence in LCC-TAFs is driven by heterotypic signaling. In addition, senescent fibroblasts provided selective growth and invasive advantages to LCC cells in culture compared to normal fibroblasts. Likewise, senescent fibroblasts enhanced tumor growth and lung dissemination of tumor cells when co-injected with LCC cells in nude mice beyond the effects induced by control fibroblasts. These results define the subtype-specific aberrant phenotypes of lung TAFs, thereby challenging the common assumption that lung TAFs are a heterogeneous myofibroblast-like cell population regardless of their subtype. Importantly, because LCC often distinguishes itself in the clinic by its aggressive nature, we argue that senescent TAFs may contribute to the selective aggressive behavior of LCC tumors.

  18. Desmocollin-3: a new marker of squamous differentiation in undifferentiated large-cell carcinoma of the lung.

    PubMed

    Monica, Valentina; Ceppi, Paolo; Righi, Luisella; Tavaglione, Veronica; Volante, Marco; Pelosi, Giuseppe; Scagliotti, Giorgio V; Papotti, Mauro

    2009-05-01

    Lung cancer classification in small-cell and non-small-cell types was recently challenged by data on the differential efficacy of new cytotoxic agents in specific histotypes. An accurate histotype definition has therefore gained interest in both preoperative and surgical materials, but is a hard task especially in undifferentiated large-cell tumors lacking morphological signs of squamous or glandular differentiation. The responsiveness of these latter subtypes to new drugs apparently more selective for adenocarcinomas or squamous carcinomas is not fully understood, also due to the heterogeneity of diagnostic criteria for this tumor entity. Current immunohistochemical markers are not fully specific and new molecules are to be explored. On the basis of gene expression profiling data, reporting a remarkable differential expression of desmocollin-3 (a protein localized in desmosomal junctions of stratified epithelial) between adeno- and squamous cancers, we immunostained 62 cases of resected undifferentiated large-cell lung carcinomas for desmocollin-3 (and for TTF-1, p63 and mucin stain), to test its ability to identify a (residual) squamous phenotype, if present. Desmocollin-3 was expressed in almost half of the undifferentiated large-cell cancers and was mutually exclusive with TTF-1 (positive in 39%; the remaining 18 % of cases was double negative). Special large-cell carcinoma variants expressed desmocollin-3 in 6 of 6 basaloid, 7 of 12 clear-cell types, again mutually exclusive with TTF-1 expression. None of seven sarcomatoid carcinomas reacted for either marker. In 31 cytological samples diagnosed as 'non-small-cell lung carcinoma', desmocollin-3 was again mutually exclusive with TTF-1 and stained all squamous carcinomas, 1 of 19 adenocarcinoma only, and 50% of large-cell carcinoma (all histologically confirmed). This combined morphophenotypic approach may represent a valid adjunct (for both surgical and cytological samples) in the selection of patients with

  19. Polysialic acid of the neural cell adhesion molecule distinguishes small cell lung carcinoma from carcinoids.

    PubMed Central

    Komminoth, P.; Roth, J.; Lackie, P. M.; Bitter-Suermann, D.; Heitz, P. U.

    1991-01-01

    The neural cell adhesion molecule (NCAM) exists in various types of neuroendocrine cells and their tumors. A typical feature of NCAM is polysialic acid, of which the chain length is developmentally regulated. The authors have performed a comparative immunohistochemical study on small cell lung carcinomas and bronchial as well as gastrointestinal carcinoids with the monoclonal antibody (MAb) 735 reactive with the long-chain form of polysialic acid. The small cell lung carcinomas, irrespective of their histological type, were positive for polysialic acid. Metastatic tumor cell complexes also exhibited immunostaining. The tumor cell-surface-associated immunostaining for polysialic acid was sensitive to endoneuraminidase. The mature and atypical bronchial and gastrointestinal carcinoids were not immunoreactive for polysialic acid. Cytoplasmic staining in groups of cells of carcinoids (2 of 28 cases) was due to nonspecific antibody binding, which could be prevented by increased ion strength. These data indicate that neuroendocrine tumors of the lung can be distinguished by their content of highly sialylated NCAM. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:1651057

  20. Cellular and humoral factors in host susceptibility to Lewis lung carcinoma.

    PubMed

    Gundersen, S; Wibe, E; Gidlund, M; Godal, T

    1981-04-01

    Cellular and humoral anti-tumour reactivity in strains of mice highly susceptible (C57Bl/6) or less susceptible (C57Cl/6 x DBA/2 = B6D2F1) to Lewis lung carcinoma (LLC) was investigated. Natural killer cell activity in a 51Cr release assay against this tumour could be demonstrated with a good correlation to in vivo susceptibility. This has not been demonstrated earlier for solid, spontaneous tumours. T-cell deficiency (congenital athymic (nude mice)) did not affect the cumulative incidence of tumour take. However, the number of lung metastases was significantly reduced in nude mice. Treatment with antilymphocyte serum (ALS) increased the susceptibility to LLC in both strains. In a soft agar colony assay a marked reduction in the number of colonies was observed when tumour cells were incubated with serum from B6D2F1 mice as compared to serum from C57Bl/6 mice, prior to seeding. Apparently naturally occurring cellular, as well as humoral effector mechanisms are involved in host resistance to Lewis lung carcinoma in the mouse.

  1. Increased chromium and nickel content in lung tissue and bronchial carcinoma

    SciTech Connect

    Kollmeier, H.; Seemann, J.W.; Mueller, K.M.R.; Rothe, G.; Wittig, P.; Schejbal, V.B.

    1987-01-01

    In 25 random autopsies, chromium (Cr) and nickel (Ni) in lung tissue and regional lymph nodes were analysed by means of flameless atomic absorption spectrometry (AAS). The subjects originate from Bochum in the Ruhr District, which is defined as a particular pollution area with locally high Cr and Ni emissions. The subjects examined from Bochum (BO) and vicinity have Cr and Ni concentrations about 5 and 6 times higher than those in a previous series form Muenster (MS) and vicinity (outside the particular pollution area), which is used for comparison purposes. BO and MS data showed an age-dependent increase of chromium and nickel in the lung, and in both data sets as well as in the combined, the Cr and Ni values showed extremely high correlations. The Cr and Ni concentrations (BO) in lung (3.47 +/- 2.53 micrograms Cr/g, 1.09 +/- 1.43 micrograms Ni/g dry weight) and lymph node tissue (6.30 +/- 3.72 micrograms Cr/g, 1.00 +/- 0.58 micrograms Ni/g dry weight) do not show any correlation. The BO data contained four cases of bronchial carcinoma (all male), three of which showed pulmonary Cr and Ni concentrations that lie clearly above the predicted level. One case of bronchial carcinoma had extremely high Cr and Ni values; an occupational exposure as dental laboratory technician is taken into consideration.

  2. S100A7 promotes lung adenocarcinoma to squamous carcinoma transdifferentiation, and its expression is differentially regulated by the Hippo-YAP pathway in lung cancer cells

    PubMed Central

    Wang, Rui; Li, Yunguang; Hu, Enze; Kong, Fei; Wang, Junhao; Liu, Jin; Shao, Qirui; Hao, Ying; He, Dacheng; Xiao, Xueyuan

    2017-01-01

    Our previous study revealed that S100A7 was selectively expressed in lung squamous cell carcinoma tissues but not in adenocarcinoma. Thus far, the functions of S100A7 in lung cancer have remained largely unknown. Here, we reveal that S100A7 overexpression facilitates the transdifferentiation from adenocarcinoma (ADC) to squamous carcinoma (SCC) in several lung cancer cells, which is confirmed by an increase in DNp63 expression and a decrease in thyroid transcription factor 1 (TTF1) and aspartic proteinase napsin (napsin A) expression. Further study finds that activation of the Hippo pathway induces S100A7 expression and further confirms that nuclear YAP acts as a repressor of S100A7 in H292 cells. Subsequently, we verify that TEAD1 is required for YAP transcriptional repression of S100A7. More importantly, we determine that S100A7 overexpression partially rescues lung ADC to SCC transdifferentiation inhibited by YAP overexpression in all tested cells, suggesting that S100A7 and YAP have the opposite effects on lung ADC to SCC conversion. Taken together, our study demonstrates for the first time that S100A7 not only functions as a facilitator of adenous-squamous carcinoma phenotypic transition in lung cancer cells but also that its expression is differentially regulated by the Hippo-YAP pathway. PMID:28177901

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

    PubMed Central

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

    1989-01-01

    Activation of protooncogenes 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. Furthermore, in 7 of these 8 squamous-cell carcinomas, loss of heterozygosity from chromosome 17 was accompanied by loss of DNA sequences from chromosome 11. The spectrum of allelic sequences lost from chromosome 11 was, however, similar in every type of carcinoma studied, and the data show two regions commonly deleted from chromosome 11 (11pter-p15.5 and 11p13-q13) that may have a role in the pathogenesis of all these types of non-small-cell bronchogenic carcinoma. Loss of DNA sequences from chromosome 3 was seen in 16 of 31 cases where the constitutive DNA was heterozygous-i.e., informative. These data included only 6 of 16 cases where loss of heterozygosity involved a chromosomal locus previously shown to be lost consistently in small-cell lung cancer (DNF15S2). 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. Images PMID:2567993

  4. Analysis of Fifty Hotspot Mutations of Lung Squamous Cell Carcinoma in Never-smokers

    PubMed Central

    2017-01-01

    Smoking is the major risk factor for lung squamous cell carcinoma (SCC), although a small number of lung SCCs occurs in never-smokers. The purpose of this study was to compare 50 hotspot mutations of lung SCCs between never-smokers and smokers. We retrospectively reviewed the medical records of patients newly diagnosed with lung SCC between January 1, 2011 and December 31, 2013 in the Seoul National University Hospital. Formalin-fixed, paraffin-embedded tumor samples were used for analysis of hotspot mutations. Fifty cancer-related genes in never-smokers were compared to those in ever-smokers. Of 379 lung SCC patients, 19 (5.0%) were never-smokers. The median age of these 19 patients was 67 years (interquartile range 57–73 years), and 10 of these patients were women (52.5%). The incidence rates of stage I, II, III, and IV disease in this group were 26.4%, 5.3%, 31.6%, and 36.8%, respectively, and sequencing was performed successfully in 14 cases. In the 26 lung SCC tumor samples (12 from never-smokers and 14 from ever-smokers) sequenced using personal genome machine, the most common mutations were in TP53 (75.0%), RAS (66.7%), and STK11 (33.3%), but mutations were also found in EGFR, KIT, and PTEN. The distribution of hotspot mutations in never-smokers was similar to that in ever-smokers. There was no significant difference in overall survival between the 2 groups. The 50 hotspot mutations of lung SCC in never-smokers were similar to those of ever-smokers. PMID:28145643

  5. Pleomorphic carcinoma of the lung associated with loss of heterozygosity of p53 gene.

    PubMed

    Arita, Norimasa; Mikami, Yoshiki; Yoshida, Minako; Konishi, Ichiro; Horiike, Norio; Miyauchi, Katsutoshi; Miyazaki, Tatsuhiko; Nose, Masato; Ono, Masao

    2005-06-01

    We report a case with pleomorphic carcinoma of the lung in a 70-year-old man. Pleomorphic carcinoma is characterized by a heterogenous composition that includes epithelial and mesechymal malignancies. In the present case, the tumor was composed of a mixture of unequivocal squamous cell carcinoma and spindle cell components resembling sarcomatous overgrowth. The spindle component did not include a heterologous mesenchymal element characterized by overt differentiation for bone, cartilage, neuron or muscle tissue. To evaluate a state of differentiation of the spindle cell component, we immunohistochemically examined expression of the antigens including vimentin, cytokeratin, sarcomeric actin, alpha-smooth muscle actin, S-100 protein, CD34, Factor VIII, and CD68. The results showed sole expression of vimentin in the spindle cell component, suggesting an immature state of the mesenchymal lineage. Furthermore, the spindle cell component of this case was genetically characterized by loss of heterozygosity (LOH) at a codon 234 of exon 7 of the p53 gene. This mutation causes an amino-acid replacement (Tyr to Cys), which was previously proven to attenuate p53 function. The present case may suggest a relation between somatic alteration of the p53 gene and histogenesis of pleomorphic carcinoma.

  6. Human Lung Carcinoma Reaction against Metabolic Serum Deficiency Stress

    PubMed Central

    Nakhjavani, Maryam; Nikounezhad, Nastaran; Ashtarinezhad, Azadeh; Shirazi, Farshad H.

    2016-01-01

    Cancer treatment is still of the greatest challenges that health care providers and patients are facing. One of the unsolved problems in cancer treatment is cells’ reaction to metabolic stress caused by harsh nutritional conditions around tumor. In order to be able to treat this disease properly, it is important to understand the true nature of the disease. In fact, the cells inside the central part of the tumor lack sufficient access to blood vessels, nutrients, and growth signals. After tumor shrinkage, the cells are exposed to favorable environmental conditions and might regrow and cause tumor recurrence. The main purpose of this study was to investigate the effect of serum starvation, as a type of metabolic stress, on human lung cancer cell line, A549. These cells were treated with 10% (control), 0.5% and 0.25% serum for 1 to 5 days. At 24 h intervals, the cells were released with 10% serum supplemented media. Starved or released cells were studied for their cycle and morphology. The results showed that the cells were actually arrested at G1 phase and following exposure to optimal conditions, the cells could be back to their cycle again. Furthermore, sub-G1 apoptotic cells population was not increased within the starvation period, while control cells had significant increase in sub-G1 cells. Morphological studies also showed that starved cells could make denser colonies while control cells were entering death phase. These observations provide some evidence for the generation of some effective resistance phenomena in cancer cells against harsh metabolic conditions. PMID:28243278

  7. Metastatic lymphoepithelioma-like carcinoma of the lung treated with nivolumab: a case report and focused review of literature

    PubMed Central

    Kim, Chul; Rajan, Arun; DeBrito, Pedro A.

    2016-01-01

    In recent years, significant advances have been made in cancer immunotherapy. Here, we present the first report of a patient with lymphoepithelioma-like carcinoma (LELC) of the lung, an Epstein-Barr virus (EBV)-associated lung cancer, who was treated with nivolumab, a fully human IgG4 anti-PD-1 monoclonal antibody. We also carry out a focused review to identify and examine studies of LELC of the lung in the literature. This case report highlights the need to further assess the role of immune checkpoint inhibitors in LELC of the lung. PMID:28149767

  8. Case report demonstrating effectiveness of sorafenib in multiple lung and bone metastases of renal cell carcinoma

    PubMed Central

    HOSHI, MANABU; OEBISU, NAOTO; TAKADA, JUN; IWAI, TDASHI; NAKAMURA, HIROAKI

    2015-01-01

    The current study presents the case of a 59-year-old male with advanced-stage renal cell carcinoma and bone metastases in the proximal femur and ilium (cT3aN3M1; stage IV). Resection of the primary renal cell cancer and palliative surgery with a γ-nail for an impending fracture of the right proximal femur were performed, followed by radiotherapy. Sorafenib, a multi-kinase inhibitor that blocks the raf and tyrosine kinases of the vascular endothelial and platelet-derived growth factor receptors, was administered for 9 months, resulting in a marked improvement in the metastatic ilium and a reduction in the extent of the lung metastases. The patient suffered minor adverse effects, including a skin rash and mild diarrhea, but remained alive at the time of follow-up at 36 months post-surgery. Sorafenib demonstrated efficacy against the bone metastasis of metastatic renal cell carcinoma. PMID:25663922

  9. High-grade neuroendocrine carcinomas of the lung highly express enhancer of zeste homolog 2, but carcinoids do not.

    PubMed

    Findeis-Hosey, Jennifer J; Huang, Jiaoti; Li, Faqian; Yang, Qi; McMahon, Loralee A; Xu, Haodong

    2011-06-01

    Enhancer of zeste homolog 2, the catalytic subunit of polycomb repressive complex 2, is a histone methyltransferase and plays an important role in cell proliferation and cell cycle regulation. It has been shown to be overexpressed in a number of malignant neoplasms. This study aimed to determine the expression pattern of enhancer of zeste homolog 2 in neuroendocrine tumors of the lung and the potential of enhancer of zeste homolog 2 to serve as a biomarker to segregate carcinoids from high-grade neuroendocrine carcinomas. Fifty-four cases, including 25 typical carcinoids, 7 atypical carcinoids, 9 large-cell neuroendocrine carcinomas, and 13 small-cell lung carcinomas, were immunohistochemically studied using a monoclonal antibody against enhancer of zeste homolog 2. All 13 small-cell lung carcinomas demonstrated moderate to strong nuclear staining with 12 exhibiting more than 90% of tumor cells staining. All 9 large-cell neuroendocrine carcinomas were moderately to strongly positive for enhancer of zeste homolog 2, with 6 cases having staining in more than 80% of tumor cells. In contrast, all 25 typical carcinoids and 6 atypical carcinoids showed only rare scattered enhancer of zeste homolog 2-positive tumor cells, with 1 case of atypical carcinoid exhibiting moderate staining in 40% of tumor cells. A subsequent validation study of the 14 specimens of lung or mediastinal lymph node biopsy and fine-needle aspiration, including 6 small-cell lung carcinomas, 2 large-cell neuroendocrine carcinomas, 5 typical carcinoids, and 1 atypical carcinoid, was performed. Enhancer of zeste homolog 2 was diffusely and strongly positive in all small-cell lung carcinomas and large-cell neuroendocrine carcinomas, even with severe crush artifact, whereas it was only positive in rare tumor cells in carcinoids. These findings support the formulation that enhancer of zeste homolog 2 may play an important role in the regulation of biologic behavior of high-grade neuroendocrine carcinomas

  10. Primary epithelial myoepithelial carcinoma of lung, reporting of a rare entity, its molecular histogenesis and review of the literature.

    PubMed

    Arif, Farzana; Wu, Susan; Andaz, Shahriyour; Fox, Stewart

    2012-01-01

    Primary epithelial myoepithelial carcinoma of lung is a rare entity and is thought to arise from the submucosal bronchial glands distributed throughout the lower respiratory tract. Because of the rarity of this tumor, we describe one case of epithelial myoepithelial carcinoma arising in the bronchus intermedius and presenting as an endobronchial mass. A 57-year-old male patient presented with an incidental finding of an endobronchial mass located in the lumen of the right lower lobe bronchus and caused near total luminal occlusion of the bronchus. An endobronchial carcinoid tumor was entertained clinically. Subsequently the patient underwent an uneventful videothoracoscopic lobectomy of lower and middle lobes of the right lung. Morphologically and immunohistochemically the tumor was characterized by two cell populations with epithelial and myoepithelial cells forming duct-like structure. The final diagnosis of epithelial myoepithelial carcinoma of lung was rendered.

  11. CD147 promotes the proliferation, invasiveness, migration and angiogenesis of human lung carcinoma cells

    PubMed Central

    Yang, Shaoxing; Qi, Fei; Tang, Chuanhao; Wang, Hong; Qin, Haifeng; Li, Xiaoyan; Li, Jianjie; Wang, Weixia; Zhao, Changyun; Gao, Hongjun

    2017-01-01

    Cluster of differentiation (CD) 147 is a transmembrane glycoprotein that is highly expressed at the tumor cell surface, which stimulates fibroblasts to produce a large number of matrix metalloproteinases and promotes tumor invasion and metastasis and tumor-induced angiogenesis. The present study investigated the functions and the role of CD147 in the human lung carcinoma A549 cell line. The present study constructed expression and interference [small interfering (si) RNA] lentiviral vectors of CD147, which established stable overexpression and low expression of CD147 in the A549 cell line, named A549-CD147 and A549-siCD147, respectively. The differences in biological features between various levels of CD147 expression in A549 cells was investigated by cell counting kit-8 (CCK-8), Transwell, scratch and lumen formation assays. The results of the CCK-8 assay revealed that A549-CD147 cell proliferation was significantly increased and A549-siCD147 cell proliferation was decreased compared with the control groups. The A549-CD147 cells had the largest number of cells penetrating the Matrigel in the Transwell assay, which indicates that upregulation of CD147 expression increases the infiltration capacity of cells. The scratch assay revealed that A549-CD147 cells have the highest capacity for migration, while A549-siCD147 cells have the lowest. Quantitative polymerase chain reaction and western blot analysis demonstrated that vascular endothelial growth factor (VEGF) expression was proportional to the expression level of CD147 at the mRNA and protein level. The lumen formation assay revealed that the number of vessel lumens that human umbilical vein endothelial cells formed in the A549-CD147 cell supernatant was increased compared with the A549-siCD147 cells. Collectively, the present results suggest that CD147 is important in the promotion of lung carcinoma cell proliferation, invasion and metastasis and the upregulation of VEGF, which stimulates the angiogenesis of lung

  12. Review of the treatment of metastatic non small cell lung carcinoma: A practical approach

    PubMed Central

    Hirsh, Vera

    2011-01-01

    In recent years, as we have a better knowledge and understanding of the biology of non small cell lung carcinoma (NSCLC), which leads us to targeting biomarkers driving the NSCLC carcinogenesis and metastatic potential, we now have an increased number of options to offer our patients with NSCLC. We also realize the importance of distinguishing squamous and non squamous histology to guide our treatment decisions of NSCLC. The palliative care concomitant with therapies from the very start of the treatment also showed an impact on survival. This review examines the treatment options in all lines of therapy for metastatic NSCLC that have been approved in Canada, the United States, or Europe. PMID:21773076

  13. Regression of Hepatocellular Carcinoma Lung Metastases after Guyabano Fruit Extract Consumption.

    PubMed

    Gunasekaran, Senthil S; Emmadi, Rajyasree; Landers, Lisa A; Gaba, Ron C

    2016-01-01

    Hepatocellular carcinoma (HCC) is a leading cause of worldwide cancer-related mortality, and even with established treatment paradigms, its global burden demands greater research into therapeutic options. In the following case report, a patient suffering from HCC with lung metastasis demonstrated regression of metastatic disease while consuming guyabano fruit extract in the absence of conventional chemotherapy. While the antineoplastic effects of the guyabano fruit is well documented, there is sparse clinical documentation of HCC regression associated with it, and a better understanding of guyabano and its antineoplastic activity may trigger discovery of novel therapeutic options for this deadly disease.

  14. miR-448 is a novel prognostic factor of lung squamous cell carcinoma and regulates cells growth and metastasis by targeting DCLK1.

    PubMed

    Shan, Changting; Fei, Fan; Li, Fengzhu; Zhuang, Bo; Zheng, Yulong; Wan, Yufeng; Chen, Jianhui

    2017-03-15

    MicroRNA-448 (miR-448) has been showed to be low-expressed and function as tumor suppressor in most human cancers. However, there are limited reports on the clinical significance and biological function of miR-448 in lung squamous cell carcinoma. In this study, we observed that miR-448 expression was decreased in lung squamous cell carcinoma tissues and cell lines. Meanwhile, miR-448 expression associated with differentiated degree, T classification (tumor size), N classification (lymph node metastasis), M classification (distant metastasis), clinical stage and prognosis of lung squamous cell carcinoma patients. In survival analysis, low expression of miR-448 was a poor independent prognostic factor for lung squamous cell carcinoma patients. Moreover, gain-of-function and loss-of-function studies showed miR-448 acted as a tumor suppressor regulating lung squamous cell carcinoma cells growth and metastasis. Furthermore, DCLK1 has been identified as a potential target for miR-448 to regulate lung squamous cell carcinoma cells growth and metastasis. In conclusion, miR-448 low-expression was a poor prognostic factor for lung squamous cell carcinoma patients, and miR-448 served as a tumor suppressor in lung squamous cell carcinoma cells via targeting DCLK1.

  15. Metastatic squamous cell carcinoma of the anus to the lung confirmed with allelotyping.

    PubMed

    Roth, Rachel; Moffatt-Bruce, Susan; Leon, Marino E

    2014-01-01

    Histopathologic techniques are insufficient for distinguishing primary squamous cell carcinoma (SCC) from metastatic SCC, which is clinically important. A patient with SCC of the anus was found to also have SCC of the lung, and the question of metastatic versus synchronous primary diseases was raised. Immunohistochemical and hematoxylin and eosin (H&E) staining on sections of tissue could not discriminate between the two entities. Immunostain for p16 and chromogenic in situ hybridization for human papillomavirus (HPV) type 16 were positive in both tumors. Additionally, allelotyping for loss of heterozygosity displayed similar findings and confirmed the histopathological impression of anal SCC metastasis to the lung. The patient was treated with palliative chemotherapy instead of additional surgical treatment. When multiple tumors are present, determining metastatic versus synchronous primary tumors is necessary for appropriate treatment. Identification can be achieved using allelotyping for loss of heterozygosity.

  16. Paraneoplastic neurological syndrome as an initial indicator of small cell carcinoma of the lung.

    PubMed

    Porto, Lénea; Miranda, Mafalda; Gomes, Ana; André, Rui; Rodrigues, Bárbara

    2013-02-06

    Paraneoplastic syndromes are indirect manifestations of cancer due to functional peptides/hormones produced by a tumour, or due to cross reactivity between tumour and host antigens. Here the case of a 58-year-old woman presenting with ataxia, paraesthesia and subacute and progressive loss of vision is reported. The patient exhibited strong serum positivity for anti-Hu and anti-CV2 antibodies, and a chest CT scan showed a hypodense nodule in proximity of the right upper lobe bronchus and an enlarged ipsilateral paratracheal lymph node that was not visible on a lung x-ray. Histopathological examination of a biopsy specimen from this lymph node showed that small cell carcinoma of the lung was present. The patient's deficits were subsequently diagnosed as three coexisting paraneoplastic neurological syndromes (PNSs): subacute cerebellar ataxia, sensory neuropathy and retinopathy, respectively. Although rare, PNSs can be the first manifestations of cancer, and their rapid recognition facilitates an early treatment.

  17. Clubbed fingers and hypertrophic osteoarthropathy in a patient with squamous cell carcinoma of the lung.

    PubMed

    Yang, Wen-Chi; Lin, Shih-Chang; Liu, Ta-Chih; Chen, Chung-Jen; Yen, Jeng-Hsien; Ou, Tsan-Teng; Liu, Hong-Wen; Tsai, Wen-Chan

    2003-04-01

    Hypertrophic osteoarthropathy (HOA) is characterized by clubbed fingers and periosteal new bone formation. Etiologically, it can be divided into primary and secondary HOA, but its pathogenesis is uncertain. We report a 42-year-old male patient who suffered from painful clubbing fingers and toes. Serial examinations revealed periosteal new bone formation in the four limb long bones and a solid mass lesion in the right upper lung field. Pathologic examination of the resected mass lesion showed squamous cell carcinoma. After surgery and chemotherapy, the severity of clubbed fingers decreased and joint pain improved. Follow-up bone scan also suggested regression of the uptake of radioactivity in the four limb bones. We concluded that the HOA in this case was probably caused by lung cancer.

  18. Customised, Individualised Treatment of Metastatic Non-Small-Cell Lung Carcinoma (NSCLC)

    PubMed Central

    Furrukh, Muhammad; Al-Moundhri, Mansour; Zahid, Khawaja F.; Kumar, Shiyam; Burney, Ikram

    2013-01-01

    A series of phase II and randomised phase III trials in Asia and Europe have confirmed recently that advanced stage non-small-cell lung carcinoma patients with adenocarcinoma subtypes harbouring specific mutations when subjected to targeted therapy experience equivalent survival outcomes as those treated with chemotherapy and are spared from its side effects. The concept of chemotherapy for all is fading, and therapy optimisation has emerged as a paradigm shift in treatment. This article briefly describes cellular mechanisms involved in lung carcinogenesis which provide a molecular basis for targeted therapy. Advances in molecular biology have improved our understanding of mechanisms involved in primary or secondary drug resistance. Evolving biomarkers of prognostic and predictive importance, and the impact of translational research on outcomes are also covered. A marker is considered prognostic if it predicts the outcome, regardless of the treatment, and predictive if it predicts the outcome of a specific therapy. PMID:23862025

  19. Decreased lung carcinoma cell density on select polymer nanometer surface features for lung replacement therapies.

    PubMed

    Zhang, Lijuan; Chun, Young Wook; Webster, Thomas J

    2010-05-13

    Poly(lactic-co-glycolic) acid (PLGA) has been widely used as a biomaterial in regenerative medicine because of its biocompatibility and biodegradability properties. Previous studies have shown that cells (such as bladder smooth muscle cells, chondrocytes, and osteoblasts) respond differently to nanostructured PLGA surfaces compared with nanosmooth surfaces. The purpose of the present in vitro research was to prepare PLGA films with various nanometer surface features and determine whether lung cancer epithelial cells respond differently to such topographies. To create nanosurface features on PLGA, different sized (190 nm, 300 nm, 400 nm, and 530 nm diameter) polystyrene beads were used to cast polydimethylsiloxane (PDMS) molds which were used as templates to create nanofeatured PLGA films. Atomic force microscopy (AFM) images and root mean square roughness (RMS) values indicated that the intended spherical surface nanotopographies on PLGA with RMS values of 2.23, 5.03, 5.42, and 36.90 nm were formed by employing 190, 300, 400, and 530 nm beads. A solution evaporation method was also utilized to modify PLGA surface features by using 8 wt% (to obtain an AFM RMS value of 0.62 nm) and 4 wt% (to obtain an AFM RMS value of 2.23 nm) PLGA in chloroform solutions. Most importantly, lung cancer epithelial cells adhered less on the PLGA surfaces with RMS values of 0.62, 2.23, and 5.42 nm after four hours of culture compared with any other PLGA surface created here. After three days, PLGA surfaces with an RMS value of 0.62 nm had much lower cell density than any other sample. In this manner, PLGA with specific nanometer surface features may inhibit lung cancer cell density which may provide an important biomaterial for the treatment of lung cancer (from drug delivery to regenerative medicine).

  20. 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.

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

    PubMed Central

    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.

    2010-01-01

    The binding of exogenous nicotine to nicotinic acetylcholine receptors (nAChR) and the binding of endogenous acetylcholine to both nAChR and muscarinic acetylcholine receptors (mAChR) stimulates growth of both small cell and non-small cell lung carcinomas. Understanding how cholinergic signaling is upregulated in lung cancer may suggest new therapeutic approaches. Analysis of 28 squamous cell lung carcinomas (SCC) showed increased levels of a5 and β3 nAChR mRNA and increased levels of acetylcholine associated with increased levels of ChAT 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 upregulation 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 acetylcholine on growth of lung cancers may be through M3 mAChR antagonists which can limit the activation of MAPK 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 upregulated in SCC and blocking cholinergic signaling can limit basal and nicotine-stimulated growth of SCC. PMID:18559515

  2. ARF inhibits the growth and malignant progression of non-small-cell lung carcinoma.

    PubMed

    Busch, S E; Moser, R D; Gurley, K E; Kelly-Spratt, K S; Liggitt, H D; Kemp, C J

    2014-05-15

    Non-small-cell lung carcinoma (NSCLC) is among the deadliest of human cancers. The CDKN2A locus, which houses the INK4a and ARF tumor suppressor genes, is frequently altered in NSCLC. However, the specific role of ARF in pulmonary tumorigenesis remains unclear. KRAS and other oncogenes induce the expression of ARF, thus stabilizing p53 activity and arresting cell proliferation. To address the role of ARF in Kras-driven NSCLC, we compared the susceptibility of NIH/Ola strain wild-type and Arf-knockout mice to urethane-induced lung carcinogenesis. Lung tumor size, malignancy and associated morbidity were significantly increased in Arf(-/-) compared with Arf(+/+) animals at 25 weeks after induction. Pulmonary tumors from Arf-knockout mice exhibited increased cell proliferation and DNA damage compared with wild-type mice. A subgroup of tumors in Arf(-/-) animals presented as dedifferentiated and metastatic, with many characteristics of pulmonary sarcomatoid carcinoma, a neoplasm previously undocumented in mouse models. Our finding of a role for ARF in NSCLC is consistent with the observation that benign adenomas from Arf(+/+) mice robustly expressed ARF, while ARF expression was markedly reduced in malignant adenocarcinomas. ARF expression also frequently colocalized with the expression of p21(CIP1), a transcriptional target of p53, arguing that ARF induces the p53 checkpoint to arrest cell proliferation in vivo. Taken together, these findings demonstrate that induction of ARF is an early response in lung tumorigenesis that mounts a strong barrier against tumor growth and malignant progression.

  3. Whole exome sequencing of independent lung adenocarcinoma, lung squamous cell carcinoma, and malignant peritoneal mesothelioma: A case report.

    PubMed

    Vanni, Irene; Coco, Simona; Bonfiglio, Silvia; Cittaro, Davide; Genova, Carlo; Biello, Federica; Mora, Marco; Rossella, Valeria; Dal Bello, Maria Giovanna; Truini, Anna; Banelli, Barbara; Lazarevic, Dejan; Alama, Angela; Rijavec, Erika; Barletta, Giulia; Grossi, Francesco

    2016-11-01

    The presence of multiple primary tumors (MPT) in a single patient has been identified with an increasing frequency. A critical issue is to establish if the second tumor represents an independent primary cancer or a metastasis. Therefore, the assessment of MPT clonal origin might help understand the disease behavior and improve the management/prognosis of the patient.Herein, we report a 73-year-old male smoker who developed 2 primary lung cancers (adenocarcinoma and squamous cell carcinoma) and a malignant peritoneal mesothelioma (PM).Whole exome sequencing (WES) of the 3 tumors and of germline DNA was performed to determine the clonal origin and identify genetic cancer susceptibility.Both lung cancers were characterized by a high mutational rate with distinct mutational profiles and activation of tumor-specific pathways. Conversely, the PM harbored a relative low number of genetic variants and a novel mutation in the WT1 gene that might be involved in the carcinogenesis of nonasbestos-related mesothelioma. Finally, WES of the germinal DNA displayed several single nucleotide polymorphisms in DNA repair genes likely conferring higher cancer susceptibility.Overall, WES did not disclose any somatic genetic variant shared across the 3 tumors, suggesting their clonal independency; however, the carcinogenic effect of smoke combined with a deficiency in DNA repair genes and the patient advanced age might have been responsible for the MPT development. This case highlights the WES importance to define the clonal origin of MPT and susceptibility to cancer.

  4. PD-L1 expression in lung adenosquamous carcinomas compared with the more common variants of non-small cell lung cancer

    PubMed Central

    Shi, Xiaohua; Wu, Shafei; Sun, Jian; Liu, Yuanyuan; Zeng, Xuan; Liang, Zhiyong

    2017-01-01

    Lung adenosquamous cell carcinomas (ASCs) is a rare variant of NSCLC with a poorer prognosis and fewer treatment option than the more common variants. PD-L1 expression is reported to be the predictor of clinical response in trials of NSCLC. In our study, PD-L1 expression was evaluated via immunohistochemistry using a specific monoclonal antibody (SP263), and PD-L1 mRNA expression was evaluated via in situ hybridization. This study included 51 ASCs, 133 lung adenocarcinomas, and 83 lung squamous cell carcinomas (SCC). Similar results were obtained for PD-L1 expression measured at the mRNA and protein level (k coefficient, 0.851, P = 1.000). PD-L1 expression was significantly higher in the squamous versus glandular component of the 36 ASCs in which the components were analyzed separately. The PD-L1 expression rate was similar in the squamous cell component of ASCs and lung SCC (38.89% vs. 28.92%, P = 0.293), so does the adenocarcinoma component of ASCs and lung adenocarcinomas (11.11% vs 13.53%, P = 1.000). PD-L1 expression correlated significantly with lymphovascular invasion (P = 0.016), but not with EGFR, KRAS, and ALK mutations in lung ASCs. Anit-PD-L1 is a promising treatment option in lung ASC cases in which PD-L1 upregulated and EGFR mutations are present. PMID:28387300

  5. Lung Adenocarcinoma and Squamous Cell Carcinoma Gene Expression Subtypes Demonstrate Significant Differences in Tumor Immune Landscape.

    PubMed

    Faruki, Hawazin; Mayhew, Gregory M; Serody, Jonathan S; Hayes, D Neil; Perou, Charles M; Lai-Goldman, Myla

    2017-06-01

    Molecular subtyping of lung adenocarcinoma (AD) and lung squamous cell carcinoma (SCC) reveal biologically diverse tumors that vary in their genomic and clinical attributes. Published immune cell signatures and several lung AD and SCC gene expression data sets, including The Cancer Genome Atlas, were used to examine immune response in relation to AD and SCC expression subtypes. Expression of immune cell populations and other immune related genes, including CD274 molecule gene (CD274) (programmed death ligand 1), was investigated in the tumor microenvironment relative to the expression subtypes of the AD (terminal respiratory unit, proximal proliferative, and proximal inflammatory) and SCC (primitive, classical, secretory, and basal) subtypes. Lung AD and SCC expression subtypes demonstrated significant differences in tumor immune landscape. The proximal proliferative subtype of AD demonstrated low immune cell expression among ADs whereas the secretory subtype showed elevated immune cell expression among SCCs. Tumor expression subtype was a better predictor of immune cell expression than CD274 (programmed death ligand 1) in SCC tumors but was a comparable predictor in AD tumors. Nonsilent mutation burden was not correlated with immune cell expression across subtypes; however, major histocompatibility complex class II gene expression was highly correlated with immune cell expression. Increased immune and major histocompatibility complex II gene expression was associated with improved survival in the terminal respiratory unit and proximal inflammatory subtypes of AD and in the primitive subtype of SCC. Molecular expression subtypes of lung AD and SCC demonstrate key and reproducible differences in immune host response. Evaluation of tumor expression subtypes as potential biomarkers for immunotherapy should be investigated. Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

  6. The changing anatomic position of squamous cell carcinoma of the lung – a new conundrum

    PubMed Central

    Krimsky, William; Muganlinskaya, Nargiz; Sarkar, Saiyad; Vulchi, Manasa; Patel, Pujan; Rao, Suman; Hammer, Joel; Evans, Ruth; Qureshi, Muhammad; Harley, Daniel

    2016-01-01

    Background Traditionally, squamous cell carcinoma (SCC) of the lung is a central rather than a peripheral form of lung cancer. Rates of SCC in the lung periphery are typically sited in the 15–30% range. Recently, we observed that a significant portion of newly diagnosed SCC was located on a periphery. A comprehensive review of the tumor data at our facility, a busy teaching hospital with a large cohort of cancer patients, was undertaken to assess whether there had been a substantive change in the traditional epidemiologic distributions of the lung cancer, specifically with respect to SCC. Given the differences in cell biology and carcinogenesis of central versus peripheral SCC, a potential epidemiologic shift might suggest a change in tumor biology. Methods From May 12, 2012 through May 13, 2013, all histopathologically confirmed diagnoses of SCC of the lung were retrospectively reviewed. Each patient's lesion was then classified as peripheral or central based on CT evidence. Results A total of 56 patients were diagnosed with SCC. Of these, 55% (n=31) had peripheral and 45% (n=25) had central SCC. Twenty-nine patients did not have any prior history of malignancy. Of this subset of patients, 62% (n=18) had peripheral SCC, and 38% (n=11) had central SCC. Conclusion Our findings appear to correlate with our initial observation that, within our institution, there has been a substantive shift in the traditional distribution of SCC with the majority of these cancers now being diagnosed in the lung periphery as opposed to the more central locations. PMID:27987285

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

    PubMed Central

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

    2016-01-01

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

  8. An investigation of the chest radiographs in a controlled trial of busulphan, cyclophosphamide, and a placebo after resection for carcinoma of the lung.

    PubMed Central

    Stott, H; Stephens, R; Fox, W; Simon, G; Roy, D C

    1976-01-01

    A standard series of radiographs of 588 patients allocated at random to treatment with busulphan (B patients), cyclophosphamide (C patients), or a placebo (P patients) for two years after surgery for bronchial carcinoma were viewed in three stages (following procedures which avoided bias) by an independent assessor, unaware of the allocated treatment of any patient, with a view to identifying pulmonary changes due to busulphan. Radiographic appearances consistent with busulphan lung were not reported in any of the 195 B patients (receiving a mean dosage of 464 mg of busulphan over 301 days) or of the 192 C patients but were present in one of the 201 patients receiving placebo. PMID:781905

  9. 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

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

    PubMed

    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.

  11. 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.

  12. 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.

  13. FGFR1 amplifications in squamous cell carcinomas of the lung: diagnostic and therapeutic implications

    PubMed Central

    Schildhaus, Hans-Ulrich; Nogova, Lucia; Wolf, Jürgen

    2013-01-01

    Fibroblast growth factor receptor 1 (FGFR1) is a type 4 receptor tyrosine kinase. The receptor and its ligands play an important role in development and physiology. However, constitutive activation of FGFR1 by gene amplification, translocation or mutation is associated with various malignancies as, for example, breast cancer or myeloproliferative diseases. We have recently reported that FGFR1 amplification occurs in 20% of pulmonary squamous cell carcinomas, and preclinical tests have shown that these alterations are therapeutically tractable. These findings make FGFR1 amplification a potential biomarker for lung cancer treatment. Squamous cell carcinomas of the lung are characterized by an uneven FGFR1 gene copy number distribution. Therefore, fluorescence in situ hybridization assays need to address focality and heterogeneity of FGFR1 in these tumors. Here, we review our proposal for a reading and evaluation strategy. Furthermore, we highlight the emerging landscape of clinical trials with selective and unselective FGFR inhibitors and provide first response data from early clinical trials. PMID:25806220

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

    PubMed

    Padjas, Anna; Lesisz, Dominika; Lankoff, Anna; Banasik, Anna; Lisowska, Halina; Bakalarz, Robert; Góźdź, Stanisław; Wojcik, Andrzej

    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.

  15. 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

    2015-12-20

    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.

  16. IGFBP7 functions as a potential lymphangiogenesis inducer in non-small cell lung carcinoma.

    PubMed

    Zhao, Weipeng; Wang, Jun; Zhu, Bo; Duan, Yuzhong; Chen, Fanglin; Nian, Weiqi; Sun, Jianguo; Zhang, Bicheng; Tong, Zhongsheng; Chen, Zhengtang

    2016-03-01

    Lymphangiogenesis is not only involved in the processes of embryonic development, tissue repair and chronic inflammation, but also in tumor lymphatic metastasis. Metastatic tumor cells spreading through lymphatic vessels occur in non-small cell lung carcinoma (NSCLC), with regional lymph node metastasis often being the most important prognostic factor for carcinoma patients. Recent research has identified a range of lymphangiogenic growth factors that could conceivably play a great role in promoting tumor lymphangiogenesis and lymphatic metastasis. The most extensively accepted signaling pathways promoting lymphangiogenesis in tumors include the secreted lymphangiogenic proteins: vascular endothelial growth factor-C (VEGF-C) and VEGF-D, and their cognate receptor on lymphatic endothelium VEGF receptor-3 (VEGFR-3). Targeting VEGF pathway strategy sometimes failed to decrease tumor metastasis in vivo experiments and clinical trials. It is unclear whether the tumor cells induced the lymphangiogenesis process, while VEGF pathway could not completely illustrate the mechanism of tumor cell lymphatic metastasis. To explore the novel tumor lymphangiogenesis targets, we screened 181 candidate genes between high lymphatic vascular density (LVD) and low LVD in lung adenocarcinomas using Human Genome U133 Plus 2.0 Microarray. Insulin-like growth factor binding protein 7 (IGFBP7) was proven to be associated with metastatic clinicopathological features and high LVD. Furthermore, by assessing the capability of lymphatic endothelial cell forming lymphatic vessel-like structures in vitro, it appears to enhance lymphangiogenesis.

  17. Does Strong and Diffuse PAX-8 Positivity Occur in Primary Lung Carcinoma? An Immunohistochemical Study of 418 Cases and Review of the Literature.

    PubMed

    McHugh, Kelsey E; Arrossi, Andrea V; Farver, Carol F; Mukhopadhyay, Sanjay

    2017-08-02

    Although rare cases of PAX-8-positive primary lung carcinoma have been reported, details of staining distribution and intensity in such cases are limited. The aim of this study was to determine whether strong and diffuse PAX-8 staining can occur in primary lung carcinoma. Immunohistochemical staining for PAX-8 (Rabbit polyclonal, 10336-1-AP; Proteintech) was performed on whole-tissue sections from 418 resected primary lung carcinomas. PAX-8 was positive in 5/418 (1.2%) cases, all of which were large cell neuroendocrine carcinomas. Staining was weak to moderate in all 5 cases, and was seen in 5% to 30% of tumor cells. All other primary lung carcinomas (413/418) were negative for PAX-8. This study-the largest series of PAX-8-stained whole-tissue sections of primary lung carcinoma to date-shows that strong and diffuse staining for PAX-8 does not occur in primary lung carcinoma of any type. This staining pattern in a carcinoma in a lung specimen provides strong evidence of nonpulmonary origin.

  18. Standard Specimen Reference Set: Lung — EDRN Public Portal

    Cancer.gov

    The NCI/EDRN/SPORE Lung Cancer Biomarkers Group (LCBG) began its activities back in November 2004 and developed clear objectives and strategies on how to begin validating a series of candidate biomarkers for the early detection of lung cancer. The initial goal of the LCBG is to develop the requisite sample resources to validate serum/plasma biomarkers for the early diagnosis of lung cancer. Researchers may use these resources and process for continued biomarker refinement but this is not the primary activity of the LCBG.

  19. The maximum standardized FDG uptake on PET-CT in patients with non-small cell lung cancer

    PubMed Central

    2013-01-01

    Background Non-small cell lung cancer (NSCLC) accounts for approximately 80% of new diagnoses of pulmonary carcinoma. This study investigated the correlation between 18 F-fluorodeoxyglucose uptake in computerized tomography integrated positron emission tomography and tumor size, lymph node metastasis, and distant metastasis in patients with NSCLC. Methods The records of 151 NSCLC patients (139 male, 12 female; mean age 59.60 years) were evaluated retrospectively. Results Forty-one cases were adenocarcinomas; 45 squamous cell carcinomas; and 65 unspecified NSCLC. When the cases were categorized according to tumor size (group 1, ≤ 3 cm; group 2, > 3 and ≤ 5 cm; group 3, > 5 cm), the maximum standardized uptake value (SUVmax) was significantly lower in groups 1 and 2 compared with group 3 (p = 0.006 for each). Considering all cases, tumor SUVmax was not correlated with age, gender, or histopathological type. Lymph node metastases were pathologically proven in 24 cases: 24% of these were adenocarcinomas, 6% squamous cell carcinomas, and 16% unspecified NSCLC. Neither lymph node involvement nor distant metastases were correlated with tumor SUVmax, although lymph node size was positively correlated with lymph node SUVmax (r = 0.775; p < 0.001). Conclusions SUVmax was significantly associated with tumor size, but not with distant metastases or lymph node involvement. Therefore, SUVmax on positron emission tomography is not predictive of the presence of metastases. PMID:24148271

  20. Pleomorphic Carcinoma of the Lung with High Serum Beta-human Chorionic Gonadotropin Level and Gynecomastia

    PubMed Central

    Hasbal, Baris; Aydin, Kubra; Bozkurt, Mustafa; Namal, Esat; Oz, Buge; Kaynak, Kamil; Demir, Gokhan

    2010-01-01

    Although gynecomastia is a well-defined paraneoplastic syndrome in patients with non-small cell lung cancer, the association with pleomorphic carcinoma has not been reported. A 50-yr-old man presented with bilateral gynecomastia and elevated serum beta-human chorionic gonadotropin (βhCG) level. Chest tomography showed a mass in the right middle lobe. Right middle lobectomy and mediastinal lymph node dissection were performed. βhCG levels decreased rapidly after surgery. Histological examination revealed pleomorphic carcinoma with positive immunostaining for βhCG. Serum βhCG levels began to increase gradually on postoperatively 4th month. Computed tomography detected recurrence and chemotherapy was started. After second cycle of chemotherapy, βhCG levels decreased dramatically again and tomography showed regression in mass. Patient died 6 months later due to brain metastasis. βhCG expression may be associated with aggressive clinical course and increased risk of recurrence, also βhCG levels may be used to evaluate therapy response in patients with pleomorphic carcinoma. PMID:21165299

  1. Voriconazole Exposure and Risk of Cutaneous Squamous Cell Carcinoma, Aspergillus Colonization, Invasive Aspergillosis and Death in Lung Transplant Recipients.

    PubMed

    Mansh, M; Binstock, M; Williams, K; Hafeez, F; Kim, J; Glidden, D; Boettger, R; Hays, S; Kukreja, J; Golden, J; Asgari, M M; Chin-Hong, P; Singer, J P; Arron, S T

    2016-01-01

    Voriconazole is a triazole antifungal used to prevent and treat invasive fungal infections after lung transplantation, but it has been associated with an increased risk of developing cutaneous squamous cell carcinoma (SCC). Despite widespread use, there are no clear guidelines for optimal prophylactic regimens that balance the competing risks and benefits. We conducted a retrospective cohort study of all lung transplant recipients at the University of California, San Francisco, who were transplanted between October 1991 and December 2012 (n = 455) to investigate whether voriconazole exposure affected development of SCC, Aspergillus colonization, invasive aspergillosis and all-cause mortality. Voriconazole exposure was associated with a 73% increased risk of developing SCC (hazard ratio [HR] 1.73; 95% confidence interval [CI]: 1.04-2.88; p = 0.03), with each additional 30-day exposure at the standard dose increasing the risk by 3.0% (HR 1.03; 95% CI: 1.02-1.04; p < 0.001). Voriconazole exposure reduced risk of Aspergillus colonization by 50% (HR 0.50; 95% CI: 0.34-0.72; p < 0.001), but we were underpowered to detect risk reduction for invasive aspergillosis. Voriconazole exposure significantly reduced all-cause mortality among subjects who developed Aspergillus colonization (HR 0.34; 95% CI: 0.13-0.91; p = 0.03) but had no significant impact on those without colonization. Physicians should consider patient-specific factors that modify the potential risks and benefits of voriconazole for the care of lung transplant recipients.

  2. 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.

  3. 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.

  4. The use of P63 immunohistochemistry for the identification of squamous cell carcinoma of the lung.

    PubMed

    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

    2010-08-17

    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. 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. 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. P63 IHC is useful for the identification of lung SCCs.

  5. 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. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. 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

  7. 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.

  8. Immunotherapy for Lewis lung carcinoma utilizing dendritic cells infected with CK19 gene recombinant adenoviral vectors

    PubMed Central

    SUN, Q.F.; ZHAO, X.N.; PENG, C.L.; HAO, Y.T.; ZHAO, Y.P.; JIANG, N.; XUE, H.; GUO, J.Z.; YUN, C.H.; CONG, B.; ZHAO, X.G.

    2015-01-01

    Dendritic cells (DCs) as 'professional' antigen-presenting cells (APCs) initiate and regulate immune responses to various antigens. DC-based vaccines have become a promising modality in cancer immunotherapy. Cytokeratin 19 (CK19) protein is expressed at high levels in lung cancer and many other tumor cells, suggesting CK19 as a potential tumor-specific target for cancer immune therapy. We constructed a recombinant adenoviral vector containing the CK19 gene (rAd-CK19). DCs transfected with rAd-CK19 were used to vaccinate C57BL/6 mice bearing xenografts derived from Lewis lung carcinoma (LLC) cells. The transfected DCs gave rise to potent CK19-specific cytotoxic T lymphocytes (CTLs) capable of lysing LLC cells. Mice immunized with the rAd-CK19-DCs exhibited significantly attenuated tumor growth (including tumor volume and weight) when compared to the tumor growth of mice immunized with rAd-c DCs or DCs during the 24-day observation period (P<0.05). The results revealed that the mice vaccinated with the rAd-CK19-DCs exhibited a potent protective and therapeutic antitumor immunity to LLC cells in the subcutaneous model along with an inhibitive effect on tumor growth compared to the mice vaccinated with the rAd-c DCs or DCs alone. The present study proposes a meaningful mode of action utilizing rAd-CK19 DCs in lung cancer immunotherapy. PMID:26323510

  9. Scintillation Scanning of Lungs in Preoperative Assessment of Carcinoma of Bronchus

    PubMed Central

    Walker, R. H. Secker; Provan, J. L.

    1969-01-01

    Lung scans with the use of macroaggregated human serum albumin labelled with technetium-99m were carried out in 52 patients before thoracotomy. Forty-three patients had carcinoma of the bronchus. Tumours less than 2 cm. in diameter on the chest radiograph were not detected. Larger tumours showed defects in perfusion, ranging in size from the mass seen on the chest radiograph to almost absent perfusion of the entire lung. The extent of the defect in perfusion was closely related to involvement of the pulmonary vessels at the hilum by distortion, compression, or invasion by the tumour. Bronchial obstruction played a less important part in producing the defects. The larger the defect in perfusion the greater was the involvement of the hilar and mediastinal structures and the more extensive was the surgery required. When perfusion of the affected lung was less than one-third of the total the tumour was found to be unresectable. ImagesFig. 1Fig. 2Fig. 3Fig. 4 PMID:5800342

  10. Spinal Cord Ischemia Secondary to Epidural Metastasis from Small Cell Lung Carcinoma.

    PubMed

    Yasui, Hirotoshi; Ozawa, Naoya; Mikami, Satoshi; Shimizu, Kenji; Hatta, Takahiro; Makino, Nami; Fukushima, Mayu; Baba, Satoshi; Makino, Yasushi

    2017-03-17

    BACKGROUND Spinal cord ischemia is an uncommon event that is mainly caused by dissociation of the ascending aorta as a complication after aortic surgery. Spinal arteries can develop collateral circulation; therefore, the frequency of spinal infarction is about 1% of that in the brain. Few cases of spinal cord ischemia developing in the course of lung cancer have been reported. CASE REPORT We presented the case of a 56-year-old man with small cell lung carcinoma, cT4N2M1a (stage IV). He was treated with irradiation and 2 courses of platinum and etoposide combination chemotherapy. He complained of back pain followed by quadriplegia and sensory disturbance after cessation of chemotherapy. With a diagnosis of spinal cord metastasis, steroids were administered. However, diaphragmatic paralysis appeared a few hours later. He was started on palliative care and died after 6 days. Autopsy showed epidural metastasis and spinal ischemia at the C5 level. CONCLUSIONS Epidural metastasis can compress the spinal artery and cause circulatory disorders. Spinal cord ischemia should be considered in patients with rapid paralysis in the course of lung cancer.

  11. NSD3-NUT-expressing midline carcinoma of the lung: first characterization of primary cancer tissue.

    PubMed

    Suzuki, Shioto; Kurabe, Nobuya; Ohnishi, Ippei; Yasuda, Kazumasa; Aoshima, Yoichiro; Naito, Masaaki; Tanioka, Fumihiko; Sugimura, Haruhiko

    2015-05-01

    Nuclear protein in testis (NUT) midline carcinoma (NMC) is a rare, aggressive malignancy. Only two pediatric and three adult cases of pulmonary NMCs have been documented. In more than two-thirds of NMC cases, a gene fusion between NUT and BRD4 or BRD3 has been documented; other fusions are rare. A 36-year-old woman was admitted because of a rapidly progressing tumor of the lung with metastases to the breast and bone. A biopsy from the lung tumor revealed an undifferentiated neoplasm exhibiting round to oval nuclei with vesicular chromatin, prominent nucleoli, and scant cytoplasm. Immunohistochemical staining demonstrated focal EMA, cytokeratin AE1/AE3, cytokeratin CAM 5.2, p63, CD138, and vimentin positivity. Finally, the nuclear staining pattern for NUT confirmed a histopathological diagnosis of NMC. A 5'- rapid amplification of the cDNA end (RACE) procedure successfully identified the partner of the NUT translocation as NSD3, a recently discovered partner. Fluorescence in situ hybridization confirmed the NSD3-NUT gene rearrangement, whereas a BRD3/4-NUT fusion gene was not detected. We herein describe the first case of an NSD3-NUT-expressing NMC of the lung. The further accumulation of variant NMCs should provide clues to the establishment of new individualized therapy for NMCs. Copyright © 2014 Elsevier GmbH. All rights reserved.

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

    PubMed

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

    1991-10-01

    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.

  13. 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

  14. Nitrosothiol-Trapping-Based Proteomic Analysis of S-Nitrosylation in Human Lung Carcinoma Cells

    PubMed Central

    Ben-Lulu, Shani; Ziv, Tamar; Weisman-Shomer, Pnina; Benhar, Moran

    2017-01-01

    Nitrosylation of cysteines residues (S-nitrosylation) mediates many of the cellular effects of nitric oxide in normal and diseased cells. Recent research indicates that S-nitrosylation of certain proteins could play a role in tumor progression and responsiveness to therapy. However, the protein targets of S-nitrosylation in cancer cells remain largely unidentified. In this study, we used our recently developed nitrosothiol trapping approach to explore the nitrosoproteome of human A549 lung carcinoma cells treated with S-nitrosocysteine or pro-inflammatory cytokines. Using this approach, we identified about 300 putative nitrosylation targets in S-nitrosocysteine-treated A549 cells and approximately 400 targets in cytokine-stimulated cells. Among the more than 500 proteins identified in the two screens, the majority represent novel targets of S-nitrosylation, as revealed by comparison with publicly available nitrosoproteomic data. By coupling the trapping procedure with differential thiol labeling, we identified nearly 300 potential nitrosylation sites in about 150 proteins. The proteomic results were validated for several proteins by an independent approach. Bioinformatic analysis highlighted important cellular pathways that are targeted by S-nitrosylation, notably, cell cycle and inflammatory signaling. Taken together, our results identify new molecular targets of nitric oxide in lung cancer cells and suggest that S-nitrosylation may regulate signaling pathways that are critically involved in lung cancer progression. PMID:28081246

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

    USDA-ARS?s Scientific Manuscript database

    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...

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

    USDA-ARS?s Scientific Manuscript database

    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...

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

    USDA-ARS?s Scientific Manuscript database

    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...

  18. [Effects of expression silencing of MAGE3 by RNA interference on location and metastasis of lung carcinoma cells].

    PubMed

    Zhang, Guo-jun; Zhao, Guo-qiang; Hu, Jun; Zhang, Shi-jie

    2006-06-13

    To construct small interfering RNA (siRNA) expression vectors targeting human MAGE3 gene and to observe the effects of gene silencing of MAGE3 by RNA interference on location and metastasis of lung carcinoma cells. MAGE3 mRNA targeted hairpin siRNA was devised and the oligonucleotide strands of DNA fragments encoding the above siRNA were synthesized. After annealing of the complementary strands, the DNA fragments were cloned into pSUPERneoGFP, followed by amplification and DNA sequencing, then transfected into human lung carcinoma NCI-H446. The expression of MAGE3 gene mRNA and protein were examined by RT-PCR and Western blotting. Colony formation assay and Boyden chamber assay were performed to detect the effects of MAGE3 on colony formation and metastasis. The DNA fragments encoding MAGE3-targeted siRNA were cloned into the pSUPERneoGFP and confirmed by restrictive enzyme digestion and DNA sequencing. RT-PCR and Western blotting revealed a strongly decreased expression level of MAGE3. The lung carcinoma cells transfected by siRNA group was significantly lower than others, an effect on its colony formation and invasiveness. The colony formation of lung carcinoma cells transfected by siRNA in soft agar and the number of cells penetrating matrigel both reduced, there is significant difference compared with untransfected group and transfected empty vector. An siRNA vector targeting human MAGE3 gene has been successfully constructed. Expression silencing of MAGE3 by RNA interference could reduce location and metastasis of lung carcinoma cells effectively.

  19. Expression and clinical significance of CXCR5/CXCL13 in human non‑small cell lung carcinoma.

    PubMed

    Singh, Rajesh; Gupta, Pranav; Kloecker, Goetz H; Singh, Shailesh; Lillard, James W

    2014-12-01

    CXCR5 and/or CXCL13 expression is elevated in certain carcinomas and lymphomas. To determine if these factors are involved in progression of non-small cell lung cancer (LuCa), we evaluated their expression in patients with various forms of this disease. Lung biopsies from patients with non-neoplastic cells (n=8), squamous cell carcinoma (SCC; n=24), or adenocarcinoma (AC; n=54) were stained for CXCR5. Histopathological analysis of these samples showed significantly higher expression of CXCR5 (p<0.001) in carcinomas (i.e., SCCs and ACs) relative to non‑neoplastic lung tissue. Nuclear and membrane CXCR5 intensities were highest in ACs, with median values of 185 and 130, respectively, followed by SCCs with median values of 170 and 110, respectively. The lowest nuclear and membrane expressions of CXCR5 were found in non-neoplastic tissues, having median values of 142 and 90, respectively. Sera from SCC patients (n=17), AC patients (n=14), and healthy controls (n=9) were tested for the presence of CXCL13. Serum CXCL13 levels in LuCa patients were higher than in healthy controls. CXCR5 expression in cell lines of human non-small cell lung carcinoma (NCI-H1915) and small cell lung carcinoma (SW-1271) were evaluated by flow cytometry. CXCR5 expression was higher in NCI-H1915 cells relative to SW-1271 cells. The functional significance of CXCR5 expression was tested in a migration assay. In response to CXCL13, more NCI-H1915 cells migrated than SW-1271 cells. These findings suggest that the CXCR5‑CXCL13 axis influences LuCa progression. After validation in larger patient groups, CXCR5 and CXCL13 may prove useful as biomarkers for LuCa. Correspondingly, blockade of this axis could serve as an effective therapy for LuCa.

  20. Suppression of prostaglandin E2 receptor subtype EP2 by PPARgamma ligands inhibits human lung carcinoma cell growth.

    PubMed

    Han, ShouWei; Roman, Jesse

    2004-02-20

    Prostaglandin E(2) (PGE(2)), a major cyclooxygenase (COX-2) metabolite, plays important roles in tumor biology and its functions are mediated through one or more of its receptors EP1, EP2, EP3, and EP4. We have shown that the matrix glycoprotein fibronectin stimulates lung carcinoma cell proliferation via induction of COX-2 expression with subsequent PGE(2) protein biosynthesis. Ligands of peroxisome proliferator-activated receptor gamma (PPARgamma) inhibited this effect and induced cellular apoptosis. Here, we explore the role of the PGE(2) receptor EP2 in this process and whether the inhibition observed with PPARgamma ligands is related to effects on this receptor. We found that human non-small cell lung carcinoma cell lines (H1838 and H2106) express EP2 receptors, and that the inhibition of cell growth by PPARgamma ligands (GW1929, PGJ2, ciglitazone, troglitazone, and rosiglitazone [also known as BRL49653]) was associated with a significant decrease in EP2 mRNA and protein levels. The inhibitory effects of BRL49653 and ciglitazone, but not PGJ2, were reversed by a specific PPARgamma antagonist GW9662, suggesting the involvement of PPARgamma-dependent and -independent mechanisms. PPARgamma ligand treatment was associated with phosphorylation of extracellular regulated kinase (Erk), and inhibition of EP2 receptor expression by PPARgamma ligands was prevented by PD98095, an inhibitor of the MEK-1/Erk pathway. Butaprost, an EP2 agonist, like exogenous PGE(2) (dmPGE(2)), increased lung carcinoma cell growth, however, GW1929 and troglitazone blocked their effects. Our studies reveal a novel role for EP2 in mediating the proliferative effects of PGE(2) on lung carcinoma cells. PPARgamma ligands inhibit human lung carcinoma cell growth by decreasing the expression of EP2 receptors through Erk signaling and PPARgamma-dependent and -independent pathways.

  1. Expression and clinical significance of CXCR5/CXCL13 in human non-small cell lung carcinoma

    PubMed Central

    SINGH, RAJESH; GUPTA, PRANAV; KLOECKER, GOETZ H.; SINGH, SHAILESH; LILLARD, JAMES W.

    2014-01-01

    CXCR5 and/or CXCL13 expression is elevated in certain carcinomas and lymphomas. To determine if these factors are involved in progression of non-small cell lung cancer (LuCa), we evaluated their expression in patients with various forms of this disease. Lung biopsies from patients with non-neoplastic cells (n=8), squamous cell carcinoma (SCC; n=24), or adenocarcinoma (AC; n=54) were stained for CXCR5. Histopathological analysis of these samples showed significantly higher expression of CXCR5 (p<0.001) in carcinomas (i.e., SCCs and ACs) relative to non-neoplastic lung tissue. Nuclear and membrane CXCR5 intensities were highest in ACs, with median values of 185 and 130, respectively, followed by SCCs with median values of 170 and 110, respectively. The lowest nuclear and membrane expressions of CXCR5 were found in non-neoplastic tissues, having median values of 142 and 90, respectively. Sera from SCC patients (n=17), AC patients (n=14), and healthy controls (n=9) were tested for the presence of CXCL13. Serum CXCL13 levels in LuCa patients were higher than in healthy controls. CXCR5 expression in cell lines of human non-small cell lung carcinoma (NCI-H1915) and small cell lung carcinoma (SW-1271) were evaluated by flow cytometry. CXCR5 expression was higher in NCI-H1915 cells relative to SW-1271 cells. The functional significance of CXCR5 expression was tested in a migration assay. In response to CXCL13, more NCI-H1915 cells migrated than SW-1271 cells. These findings suggest that the CXCR5-CXCL13 axis influences LuCa progression. After validation in larger patient groups, CXCR5 and CXCL13 may prove useful as biomarkers for LuCa. Correspondingly, blockade of this axis could serve as an effective therapy for LuCa. PMID:25271023

  2. BOK displays cell death-independent tumor suppressor activity in non-small-cell lung carcinoma.

    PubMed

    Moravcikova, Erika; Krepela, Evzen; Donnenberg, Vera S; Donnenberg, Albert D; Benkova, Kamila; Rabachini, Tatiana; Fernandez-Marrero, Yuniel; Bachmann, Daniel; Kaufmann, Thomas

    2017-11-15

    As the genomic region containing the Bcl-2-related ovarian killer (BOK) locus is frequently deleted in certain human cancers, BOK is hypothesized to have a tumor suppressor function. In the present study, we analyzed primary non-small-cell lung carcinoma (NSCLC) tumors and matched lung tissues from 102 surgically treated patients. We show that BOK protein levels are significantly downregulated in NSCLC tumors as compared to lung tissues (p < 0.001). In particular, we found BOK downregulation in NSCLC tumors of grades two (p = 0.004, n = 35) and three (p = 0.031, n = 39) as well as in tumors with metastases to hilar (pN1) (p = 0.047, n = 31) and mediastinal/subcarinal lymph nodes (pN2) (p = 0.021, n = 18) as opposed to grade one tumors (p = 0.688, n = 7) and tumors without lymph node metastases (p = 0.112, n = 51). Importantly, in lymph node-positive patients, BOK expression greater than the median value was associated with longer survival (p = 0.002, Mantel test). Using in vitro approaches, we provide evidence that BOK overexpression is inefficient in inducing apoptosis but that it inhibits TGFβ-induced migration and epithelial-to-mesenchymal transition (EMT) in lung adenocarcinoma-derived A549 cells. We have identified epigenetic mechanisms, in particular BOK promoter methylation, as an important means to silence BOK expression in NSCLC cells. Taken together, our data point toward a novel mechanism by which BOK acts as a tumor suppressor in NSCLC by inhibiting EMT. Consequently, the restoration of BOK levels in low-BOK-expressing tumors might favor the overall survival of NSCLC patients. © 2017 UICC.

  3. Comparative oncological studies of feline bronchioloalveolar lung carcinoma, its derived cell line and xenograft.

    PubMed

    Grossman, Deborah A; Hiti, Alan L; McNiel, Elizabeth A; Ye, Yin; Alpaugh, Mary L; Barsky, Sanford H

    2002-07-01

    Although certain neoplasms are unique to man, others occur across species. One such neoplasm is bronchioloalveolar lung carcinoma (BAC), a neoplasm of the Type II pneumocyte that affects humans, sheep, and small animals (dogs and cats). Human BAC occurs largely in nonsmokers. Sheep BAC is caused by the jaagsiekte retrovirus and is endemic and contagious. Feline BAC is neither endemic nor contagious and occurs sporadically and spontaneously in older purebred cats. In these respects, feline BAC is more closely similar to human BAC than sheep BAC (jaagsiekte) is. To study feline BAC further, we established the first immortal cell line (SPARKY) and transplantable scid mouse xenograft (Sparky-X) from a malignant pleural effusion of a 12-year-old Persian male with autopsy-confirmed BAC. SPARKY exhibited a Type II pneumocyte phenotype characterized by surfactant and thyroid-transcription factor-1 immunoreactivities and lamellar bodies. SPARKY's karyotype was aneuploid (66 chromosomes: 38, normal cat) and showed evidence of genomic instability analogous to human lung cancers. p53 showed a homozygous G to T transversion at codon 167, the feline equivalent of human codon 175, one of the many hot spots mutated in the lung cancers of smokers. H-ras and K-ras were not altered. By reverse transcription-PCR, SPARKY lacked expression of retroviral JSRVgag transcripts that were present in the lungs of sheep BAC (jaagsiekte). Unlike human BAC xenografts, SPARKY-X retained its unique lepidic BAC growth pattern even though it was grown in murine s.c. tissues. This property may be related to the ability of SPARKY-X to up-regulate its surfactant genes (SP-A, SP-B, and SP-D). These studies of feline BAC may allow insights into the human disease that are not possible by studying human BAC directly.

  4. Large-cell lung carcinoma with basaloid architecture and neuroendocrine differentiation: a new type of combined large-cell neuroendocrine carcinoma.

    PubMed

    Morbini, Patrizia; Inghilleri, Simona

    2011-04-01

    One of the main differential diagnostic issues in pulmonary large-cell carcinomas is that involving neuroendocrine (NE) and basaloid histotypes. The differential diagnosis of basaloid versus large-cell NE carcinoma requires immunohistochemical determination of NE markers because of morphological overlap between the 2 entities. The authors report a unique case of lung carcinoma with basaloid architecture and NE immunohistochemical features observed in a 64-year-old male smoker who underwent upper left lobectomy for a neoplastic stenosis of the lobar bronchus. The patient died 14 months after surgery. Histological examination showed multiple peripheral nodules of moderately enlarged neoplastic cells with irregular nuclei, with granular chromatin and frequent nucleoli, and diffuse in situ neoplasia involving bronchi, peribronchial glands, and small airways. Immunohistochemistry documented diffuse expression of CD56 in neoplastic cells and isolated cell groups immunoreactive for basal cell markers. The reported case was considered an as-yet-undescribed tumor showing both basaloid and NE differentiation.

  5. Valproic acid improves second-line regimen of small cell lung carcinoma in preclinical models

    PubMed Central

    Hubaux, Roland; Vandermeers, Fabian; Cosse, Jean-Philippe; Crisanti, Cecilia; Kapoor, Veena; Albelda, Steven M.; Mascaux, Céline; Delvenne, Philippe; Hubert, Pascale

    2015-01-01

    With 5-year survival rates below 5%, small cell lung carcinoma (SCLC) has very poor prognosis and requires improved therapies. Despite an excellent overall response to first-line therapy, relapses are frequent and further treatments are disappointing. The goal of the study was to improve second-line therapy of SCLC. The effect of chemotherapeutic agents was evaluated in cell lines (apoptosis, reactive oxygen species, and RNA and protein expression) and in mouse models (tumour development). We demonstrate here that valproic acid, a histone deacetylase inhibitor, improves the efficacy of a second-line regimen (vindesine, doxorubicin and cyclophosphamide) in SCLC cells and in mouse models. Transcriptomic profiling integrating microRNA and mRNA data identifies key signalling pathways in the response of SCLC cells to valproic acid, opening new prospects for improved therapies. PMID:27730151

  6. Glucose metabolism provide distinct prosurvival benefits to non-small cell lung carcinomas.

    PubMed

    Wu, Rongrong; Galan-Acosta, Lorena; Norberg, Erik

    2015-05-08

    Heterogeneity within the same tumor type has been described to be complex and occur at multiple levels. Less is known about the heterogeneity at the level of metabolism, within a tumor set, yet metabolic pathways are highly relevant to survival signaling in tumors. In this study, we profiled the glucose metabolism of several non-small cell lung carcinoma (NSCLC) cell lines and could show that, NSCLC display distinct glycolytic metabolism. Genetic and pharmacological perturbation of glycolysis was selectively toxic to NSCLCs with high rates of glycolysis. Furthermore, high expression of hexokinase-2, localized at the mitochondria, was a feature of the NSCLCs dependent on glucose catabolism. Our study provides evidence for quantitative metabolic diversity in NSCLCs and indicates that glucose metabolism provide differential prosurvival benefits to NSCLCs.

  7. 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.

  8. Signaling pathway for aloe-emodin-induced apoptosis in human H460 lung nonsmall carcinoma cell.

    PubMed

    Yeh, Feng-Tsgh; Wu, Chun-Hsiung; Lee, Hong-Zin

    2003-08-10

    Aloe-emodin (1,8-dihydroxy-3-(hydroxymethyl)-anthraquinone) is an active component from the root and rhizome of Rheum palmatum that has been reported to exhibit antitumor effects through an unknown mechanism. Our study investigated the mechanisms of aloe-emodin-induced cell death in the human lung nonsmall cell carcinoma cell line H460. Aloe-emodin (40 microM)-induced apoptosis of H460 cells involves modulation of cAMP-dependent protein kinase, protein kinase C, Bcl-2, caspase-3 and p38 protein expression. The relationship of various signals involved in cell death, such as cAMP-dependent protein kinase, protein kinase C, Bcl-2, caspase-3 and p38, has been investigated in the regulation of apoptotic cell death of aloe-emodin. We demonstrated that the expression of p38 is an important determinant of apoptotic death induced by aloe-emodin.

  9. Hormone production by cultures of small-cell carcinoma of the lung.

    PubMed

    Sorenson, G D; Pettengill, O S; Brinck-Johnsen, T; Cate, C C; Maurer, L H

    1981-03-15

    Continuous cell lines have been established from a variety of biopsy and postmortem species of tumor from patients with small-cell carcinoma of the lung (SCCL) and have been maintained over several years. The medium from the cultures has been assayed for peptide, glycoprotein, and steroid hormones. Significant amounts of 14 hormones including calcitonin, adrenocorticotropin (ACTH), parathormone, luteinizing hormone, chorionic gonadotropin, glucagon, growth hormone, somatostatin, prolactin, beta-endorpin, lipotropin, oxytocin-neurophysin, vasopressin-neurophysin, and estradiol have been demonstrated. Up to ten different hormones have been produced by a single cell line. Most produce ACTH and all evaluated so far produce estradiol. These studies indicate that cells from SCCL have a potential for producing a wide variety of hormones and that this characteristic can be maintained for prolonged periods of culture in vitro.

  10. 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.

  11. Extreme leukocytosis and leukemoid reaction associated with the lung sarcomatoid carcinoma: an unusual case report

    PubMed Central

    Wang, Danyang; Zhang, Haiyan; Yu, Fengkuan; Fang, Baijun

    2017-01-01

    Purpose To report a rare case of extreme leukocytosis and leukemoid reaction associated with lung sarcomatoid carcinoma (LSC) and increase people’s awareness of the disease. Patients and methods A 58-year-old male patient was diagnosed with LSC; however, after the end of the second course of chemotherapy, his white blood cells increased gradually without fever or use of medications such as granulocyte colony-stimulating factor and steroids. A bone marrow biopsy then confirmed it to be a leukemoid reaction. Results The patient died of multiple organ failure 2 months after being diagnosed with leukocytosis. Conclusion LSC associated with leukemoid reaction is very rare and the prognosis is poor. When a patient’s white blood cells are extremely elevated, we should think of the possible causes of the tumor itself and identify it with other diseases. However, more data and evidence are still needed to find an effective adjuvant therapy for these patients. PMID:28096688

  12. Sequential hemibody and local irradiation with combination chemotherapy for small cell lung carcinoma: a preliminary analysis

    SciTech Connect

    Powell, B.L.; Jackson, D.V. Jr.; Scarantino, C.W.; Pope, E.; Choplin, R.; Craig, J.B.; Atkins, J.N.; Cooper, M.R.; Hopkins, J.O.; McMahan, R.

    1985-03-01

    Sequential hemibody irradiation (SHB) was integrated with combination chemotherapy and local irradiation (LRT) in the induction and consolidation phases of a therapeutic protocol for small cell lung carcinoma (SCLC). Forty-one previously untreated patients were entered into this program. Among 38 evaluable patients (20 with limited disease (LD) and 18 with extensive disease (ED)), the overall response rate was 63% (90% in LD and 33% in ED patients). The estimated overall survival is 8.1 months. The major toxicity has been myelosuppression - especially thrombocytopenia. The frequency of previously described acute radiation syndromes and radiation pneumonitis associated with hemibody irradiation have been substantially decreased at the current dosage with premedication and shielding techniques.

  13. Radiotherapy in the elderly with lung carcinoma: the experience of the Italian "Geriatric Radiation Oncology Group".

    PubMed

    Gava, A; Bertossi, L; Zorat, P L; Ausili-Cefaro, G; Olmi, P; Pavanato, G; Mandoliti, G; Polico, C

    1997-01-01

    One hundred ninety-six patients aged > or = 70 years, with non small-cell lung carcinoma and no evidence of metastasis on staging, observed over a 6-month period in 20 Italian Radiotherapy Centers, were analyzed in order to assess indications for treatment, tolerance of radiotherapy (assessed in terms of completion of planned doses and toxicity), and quality of life using the Performance Status and a concise activity of life test. Of the 196 patients studied in 20 Italian Centers, 182 (98%) underwent radiotherapy, 109(60%) of whom with radical intent and 73 (40%) with palliative intent. Of 179 assessable patients undergoing radiation treatment, 163 (91%) completed the treatment as originally planned. Of the 64 assessable patients who completed palliative radiotherapy, relief of symptoms was observed in a percentage ranging from 78% to 86%. Analysis of parameters assessing the quality of life, showed no significant differences in general and functional conditions, as assessed before and upon completion of radiotherapy.

  14. Expression of vascular endothelial growth factor mRNA in non-small-cell lung carcinomas

    PubMed Central

    Fontanini, G; Boldrini, L; Chinè, S; Pisaturo, F; Basolo, F; Calcinai, A; Lucchi, M; Mussi, A; Angeletti, C A; Bevilacqua, G

    1999-01-01

    The vascular endothelial growth factor (VEGF) has been shown to be strictly related to vascular permeability and endothelial cell growth under physiological and pathological conditions. In tumour development and progression, VEGF plays a pivotal role in the development of the tumoral vascular network, and useful information in the progression of human cancer can be obtained by analysing the vascular endothelial growth factor expression of the tumours. In this study, we investigated the vascular endothelial growth factor transcript expression in non-small-cell lung carcinomas to evaluate the significance of this factor in a group of cancers in which the vascular pattern has been shown to significantly affect progression. Surgical samples of 42 patients with NSCLC were studied using reverse transcription polymerase chain reaction (PCR) analysis and in situ hybridization. Thirty-three out of 42 cases (78.6%) showed VEGF transcript expression predominantly as transcripts for the secretory forms of VEGF (isoforms 121 and 165). In situ hybridization, performed on 24 out of 42 samples, showed that the VEGF transcript expression was in several cases present in the cytoplasm both of neoplastic and normal cells, even if the VEGF mRNA was less expressed in the corresponding non-tumoral part. The VEGF 121 expression was associated with hilar and/or mediastinal nodal involvement (P = 0.02), and, taken together, the VEGF isoforms were shown to significantly influence overall (P = 0.02) and disease-free survival (P = 0.03). As a regulator of tumour angiogenesis, VEGF may represent a useful indicator of progression and poor prognosis in non-small-cell lung carcinomas. © 1999 Cancer Research Campaign PMID:9888482

  15. [Bronchioloalveolar carcinoma in Spain: a rare and different form of lung cancer].

    PubMed

    López Encuentra, Angel; Pozo Rodríguez, Francisco; Martín de Nicolás, José Luis; Villena, Victoria; Sayas Catalán, Javier

    2006-08-01

    To describe a series of cases of bronchioloalveolar carcinoma (BAC) treated surgically between 1993 and 1997 in the 19 hospitals that make up the Bronchogenic Carcinoma Cooperative Group of the Spanish Society of Pulmonology and Thoracic Surgery (GCCB-S). From a total of 2,944 cases of non-small cell lung cancer (NSCLC), 82 (3%) were BAC. The clinical characteristics and prognosis of patients with BAC were compared with those of the remaining 2,862 patients with NSCLC. The percentage of men was lower for BAC than for other types of NSCLC (64.6% compared with 93.5%; P< .001) and BAC was associated with less comorbidity (50% vs 62%; P< .05), particularly in terms of chronic obstructive pulmonary disease (33% vs 47.2%; P< .05). Other characteristics showing significant differences were the higher frequency of BAC as a chance finding and the lower likelihood of weight loss or reduced performance status at the time of diagnosis. Classification as stage cI was significantly more common in patients with BAC (87% vs 75%; P.001), and this difference between groups was more pronounced for stage pI (68.5% vs 47%; P< .01). Only taking into account patients classified as stage pI with complete resection of NSCLC and following exclusion of operative mortality, patients with BAC presented an overall 5-year survival of 65% (95% confidence interval [CI], 51%-79%), compared with a significantly lower survival of 53% (95% CI, 50%-56%; P< .05) in patients with other forms of NSCLC. In Spain, among cases of lung cancer treated by surgery, BAC is very rare (3%) and displays clinical characteristics that are different from other forms of NSCLC. Controlling for the most basic prognostic factors (stage pI and complete resection), survival is significantly higher for BAC.

  16. [Effectiveness of Nivolumab in Large-Cell Neuroendocrine Carcinoma of the Lung - A Report of Two Cases].

    PubMed

    Daido, Wakako; Yamasaki, Masahiro; Saito, Naomi; Ishiyama, Sayaka; Deguchi, Naoko; Taniwaki, Masaya; Daga, Haruko; Ohashi, Nobuyuki

    2017-01-01

    The anti-programmed death-1 antibody nivolumab is an important treatment option for non-small-cell lung carcinoma.However, its effectiveness for large-cell neuroendocrine carcinomas(LCNEC)is still controversial.Here, we report 2 cases of LCNECs that responded to nivolumab.Case 1: A 62-year-old man received chemotherapy and radiotherapy for stage III A lung adenocarcinoma.One year later, another lung lesion was observed and diagnosed as LCNEC using surgical lung biopsy.Although he subsequently received some chemotherapy regimens, the patient developed new brain metastasis, expanded mediastinal lesion, and increased levels of the tumor marker pro-gastrin releasing peptide(ProGRP).We started nivolumab as the sixth-line treatment.In response, ProGRP levels significantly decreased and the mediastinal lesion became smaller.Case 2: A 55-year-old man was diagnosed with stage III A LCNEC and received chemotherapy and radiotherapy.The primary lesion was controlled; however, lung metastases developed and chemotherapy was unable to control them.We provided treatment with nivolumab as the third-line therapy.The tumor marker ProGRP decreased and the lung metastases became smaller. Nivolumab can be a valuable treatment option for LCNEC.

  17. Developing a radiomics framework for classifying non-small cell lung carcinoma subtypes

    NASA Astrophysics Data System (ADS)

    Yu, Dongdong; Zang, Yali; Dong, Di; Zhou, Mu; Gevaert, Olivier; Fang, Mengjie; Shi, Jingyun; Tian, Jie

    2017-03-01

    Patient-targeted treatment of non-small cell lung carcinoma (NSCLC) has been well documented according to the histologic subtypes over the past decade. In parallel, recent development of quantitative image biomarkers has recently been highlighted as important diagnostic tools to facilitate histological subtype classification. In this study, we present a radiomics analysis that classifies the adenocarcinoma (ADC) and squamous cell carcinoma (SqCC). We extract 52-dimensional, CT-based features (7 statistical features and 45 image texture features) to represent each nodule. We evaluate our approach on a clinical dataset including 324 ADCs and 110 SqCCs patients with CT image scans. Classification of these features is performed with four different machine-learning classifiers including Support Vector Machines with Radial Basis Function kernel (RBF-SVM), Random forest (RF), K-nearest neighbor (KNN), and RUSBoost algorithms. To improve the classifiers' performance, optimal feature subset is selected from the original feature set by using an iterative forward inclusion and backward eliminating algorithm. Extensive experimental results demonstrate that radiomics features achieve encouraging classification results on both complete feature set (AUC=0.89) and optimal feature subset (AUC=0.91).

  18. Histochemical evidence of osteoclastic degradation of extracellular matrix in osteolytic metastasis originating from human lung small carcinoma (SBC-5) cells.

    PubMed

    Li, Minqi; Amizuka, Norio; Takeuchi, Kiichi; Freitas, Paulo H L; Kawano, Yoshiro; Hoshino, Masaaki; Oda, Kimimitsu; Nozawa-Inoue, Kayoko; Maeda, Takeyasu

    2006-02-01

    The aim of this study was to assess the dynamics of osteoclast migration and the degradation of unmineralized extracellular matrix in an osteolytic metastasis by examining a well-standardized lung cancer metastasis model of nude mice. SBC-5 human lung small carcinoma cells were injected into the left cardiac ventricle of 6-week-old BALB/c nu/nu mice under anesthesia. At 25-30 days after injection, the animals were sacrificed and their femora and/or tibiae were removed for histochemical analyses. Metastatic lesions were shown to occupy a considerable area extending from the metaphyses to the bone marrow region. Tartrate resistant acid phosphatase (TRAPase)-positive osteoclasts were found in association with an alkaline phosphatase (ALPase)-positive osteoblastic layer lining the bone surface, but could also be localized in the ALPase-negative stromal tissues that border the tumor nodules. These stromal tissues were markedly positive for osteopontin, and contained a significant number of TRAPase-positive osteoclasts expressing immunoreactivity for CD44. We thus speculated that, mediating its affinity for CD44, osteopontin may serve to facilitate osteoclastic migration after their formation associated with ALPase-positive osteoblasts. We next examined the localization of cathepsin K and matrix metallo-proteinase-9 (MMP-9) in osteoclasts. Osteoclasts adjacent to the bone surfaces were positive for both proteins, whereas those in the stromal tissues in the tumor nests showed only MMP-9 immunoreactivity. Immunoelectron microscopy disclosed the presence of MMP-9 in the Golgi apparatus and in vesicular structures at the baso-lateral cytoplasmic region of the osteoclasts found in the stromal tissue. MMP-9-positive vesicular structures also contained fragmented extracellular materials. Thus, osteoclasts appear to either select an optimized function, namely secreting proteolytic enzymes from ruffled borders during bone resorption, or recognize the surrounding extracellular

  19. A Grading System Combining Tumor Budding and Nuclear Diameter Predicts Prognosis in Resected Lung Squamous Cell Carcinoma.

    PubMed

    Kadota, Kyuichi; Miyai, Yumi; Katsuki, Naomi; Kushida, Yoshio; Matsunaga, Toru; Okuda, Masaya; Yokomise, Hiroyasu; Kanaji, Nobuhiro; Bandoh, Shuji; Haba, Reiji

    2017-06-01

    For lung squamous cell carcinomas, there are no histologic findings that have been universally accepted as prognostic factors. Tumor budding and nuclear grade have been recognized as prognostic factors in other carcinomas. In this study, we investigated whether pathologic findings could determine clinical outcome in Japanese patients with lung squamous cell carcinomas. Tumor slides from surgically resected lung squamous cell carcinomas (1999 to 2012) were reviewed (n=216). Tumors were evaluated for histologic subtypes, differentiation, tumor budding, nuclear diameter, and mitosis. Recurrence-free survival (RFS) and overall survival (OS) were analyzed using the log-rank test and the Cox proportional hazards model. Tumor budding and large nuclei were independent prognostic factors of a worse RFS (P<0.001 and P=0.002, respectively) and a worse OS (P<0.001 and P=0.038, respectively) on multivariate analysis after adjustment for pathologic stage and lymphatic invasion. However, histologic subtypes, differentiation, and mitotic count did not correlate with prognosis. A grading system combining tumor budding and nuclear diameter was an independent prognostic factors of a worse RFS (grade 2 vs. 1, hazard ratio [HR]=2.91; P<0.001, and grade 3 vs. 1, HR=7.60, P<0.001) and a worse OS (grade 2 vs. 1, HR=2.15; P=0.014, and grade 3 vs. 1, HR=4.54, P<0.001). We found that a grading system combining tumor budding and nuclear diameter was a significant prognostic factor among Japanese patients with resected lung squamous cell carcinoma.

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

    PubMed

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

    2015-04-30

    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.

  1. 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

  2. Tumor lipids and liver lipid metabolism in the model human lung carcinoma/nude mice.

    PubMed

    de Antueno, R J; Niedfeld, G; De Tomás, M E; Mercuri, O F; Quintans, C

    1987-06-01

    Tumor lipids were studied in the experimental model Human Lung Carcinoma/nude mice as well as the effect of this human neoplasm on the host liver lipid metabolism. Fatty acid profiles from tumoral lipids revealed the loss of specificity for fatty acid composition in triglycerides. Host liver fatty acid composition and cholesterol metabolism were affected by the implanted human lung tissue. A noticeable increase ratio between saturated/unsaturated fatty acids was observed in host liver fatty acid phospholipids (1.17 +/- 0.17) in comparison to control liver (0.84 +/- 0.04). Cholesterol synthesis was assessed "in vivo" by means of [14C]acetate incorporation. The specific radioactivity of [14C] cholesterol was increased by a factor of about 6 in host liver as compared with control liver. This observation along with the marked decrease in the cholesterol content of host liver and the hypocholesterolemia detected in the host mice led us to suggest an increase in the liver cholesterol catabolism promoted by the presence of the tumor.

  3. A systemic administration of liposomal curcumin inhibits radiation pneumonitis and sensitizes lung carcinoma to radiation

    PubMed Central

    Shi, Hua-shan; Gao, Xiang; Li, Dan; Zhang, Qiong-wen; Wang, Yong-sheng; Zheng, Yu; Cai, Lu-Lu; Zhong, Ren-ming; Rui, Ao; Li, Zhi-yong; Zheng, Hao; Chen, Xian-cheng; Chen, Li-juan

    2012-01-01

    Radiation pneumonitis (RP) is an important dose-limiting toxicity during thoracic radiotherapy. Previous investigations have shown that curcumin is used for the treatment of inflammatory conditions and cancer, suggesting that curcumin may prevent RP and sensitize cancer cells to irradiation. However, the clinical advancement of curcumin is limited by its poor water solubility and low bioavailability after oral administration. Here, a water-soluble liposomal curcumin system was developed to investigate its prevention and sensitizing effects by an intravenous administration manner in mice models. The results showed that liposomal curcumin inhibited nuclear factor-κB pathway and downregulated inflammatory factors including tumor necrosis factor-α, interleukin (IL)-6, IL-8, and transforming growth factor-β induced by thoracic irradiation. Furthermore, the combined treatment with liposomal curcumin and radiotherapy increased intratumoral apoptosis and microvessel responses to irradiation in vivo. The significantly enhanced inhibition of tumor growth also was observed in a murine lung carcinoma (LL/2) model. There were no obvious toxicities observed in mice. The current results indicate that liposomal curcumin can effectively mitigate RP, reduce the fibrosis of lung, and sensitize LL/2 cells to irradiation. This study also suggests that the systemic administration of liposomal curcumin is safe and deserves to be investigated for further clinical application. PMID:22679371

  4. Antitumor activity of Corynebacterium parvum and retinyl palmitate used in combination on the Lewis lung carcinoma.

    PubMed

    Pavelic, Z P; Dave, S; Bialkowski, S; Priore, R L; Greco, W R

    1980-12-01

    The effects of Corynebacterium parvum and retinyl palmitate given at various levels, schedules, and routes of administration on primary Lewis lung carcinoma and its metastases have been evaluated in C57BL/6J mice given s.c. inoculations of 5 X 10(5) tumor cells. Single i.v., but not i.p., s.c., or i.m., administration of C. parvum (0.35 mg/mouse given on Days 0, 1, or 3) reduced growth of tumor and prolonged survival time. Retinyl palmitate (3000 IU/mouse/day) given alone i.p. either before, after, or both before and after tumor inoculation showed no effect on tumor growth, survival of mice, or lung metastases. The combination of retinyl palmitate i.p. (6 daily injections of 1500 IU/mouse after tumor implantation) and C. parvum (0.175 mg/mouse) given i.v. resulted in an increase in life span over control of 146% and appeared to be therapeutically synergistic. This combination produced 90-day cures in about 20% of the treated animals, all of which were found to be tumor free. Two nonparametric statistical procedures, the Kruskal-Wallis and the Dunn test, were used to assess the effects of treatments on survival time and tumor growth and may be generally applicable to animal tumor studies. They provide multiple comparisons of different treatments and allow the inclusion of long-term survivors into the analysis.

  5. 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.

  6. 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

  7. 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

  8. Determination of safe margin in the surgical pathologic specimens of non-small cell carcinoma of the lung.

    PubMed

    Feizi, Iraj; Sokouti, Mohsen; Golzari, Samad E J; Gojazede, Morteza; Farahnak, Mohammad Reza; Hashemzadeh, Shahriar; Rahimi-Rad, Mohammad Hossein

    2013-01-01

    Local recurrences of the tumor at the surgical margin are serious problems in pulmonary resections for lung cancer. The aim of this study is to determine the involved margins and safe distances of the resection sites from tumor for prevention of local recurrences. In this prospective study, 66 patients operated for non-small cell lung carcinoma (NSCLC) from Jan 2006 to Sep 2008 were evaluated. After performing pulmonary resections, multiple biopsies were taken up from 5 mm (A), 10 mm (B), 15 mm (C), and 20 mm (D) distance from tumor. The specimens were studied histopathologically. From a total of66 patients with NSCLC admitted to our referral hospital, 25 (38%) had adenocarcinoma, 18 (27.3%) squamous cell carcinoma, 5 (7.5%) large cell carcinoma, 4 (6%) bronchoalveolar cell carcinoma, 4 (6%) adenoid cystic carcinoma, 3 (4.6%) malignant carcinoid tumor and 7 (10.6%) had metastasis. The most common symptoms were dyspnea and cough. Histopathologically tumor positive margins were found in 84.8% (A), 10.6% (B), 4.5% (C), and 0% (D). There was a significant statistically difference between tumor involvement at distances 5 mm (A) versus 10-20 mm (B-D) (P <0.001). A 20 mm distance from the gross tumor is considered as a safe surgical margin in any type of malignant pulmonary resections for prevention of local surgical recurrences if there was no pathologic examination before surgery.

  9. Plasmacytoid dendritic cells alter the antitumor activity of CpG-oligodeoxynucleotides in a mouse model of lung carcinoma.

    PubMed

    Sorrentino, Rosalinda; Morello, Silvana; Luciano, Antonio; Crother, Timothy R; Maiolino, Piera; Bonavita, Eduardo; Arra, Claudio; Adcock, Ian M; Arditi, Moshe; Pinto, Aldo

    2010-10-15

    The effect of CpG-oligodeoxynucleotides (CpG) has been studied on a number of tumors. Although CpG may facilitate tumor regression in mouse models of melanoma, its activity in lung cancer is unclear. The aim of our study was to elucidate the effect of CpG (0.5-50 μg/mouse) in a mouse model of Lewis lung carcinoma cell-induced lung cancer. Lung tumor growth increased at 3 and 7 d after a single administration of CpG. This was associated with a greater influx of plasmacytoid dendritic cells (pDCs), immature myeloid dendritic cells, and greater recruitment of regulatory T cells. Depletion of pDCs using a specific Ab (m927) reversed the immune-suppressive environment and resulted in a decreased lung tumor burden, accompanied by a greater influx of active myeloid dendritic cells and CD8(+) T cells, and a higher production of Th1- and Th17-like cytokines. Furthermore, the rate of apoptosis in the lungs of mice treated with CpG increased following the depletion of pDCs. CpG treatment alone does not lead to tumor regression in the lung. However, ablation of pDCs renders CpG a good adjuvant for lung cancer chemotherapy in this experimental model.

  10. S0819: 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

    2017-03-16

    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

  11. 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

    2008-12-05

    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.

  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. EGFR and KRAS mutations in lung carcinoma: molecular testing by using cytology specimens.

    PubMed

    Billah, Shahreen; Stewart, John; Staerkel, Gregg; Chen, Su; Gong, Yun; Guo, Ming

    2011-04-25

    The aim of this study was to validate clinical utilization of routinely prepared cytology specimens for molecular testing to detect EGFR or KRAS mutations in lung cancer. From September 2009 to April 2010, the authors collected 209 cytology specimens from patients with lung cancer at the MD Anderson Cancer Center Department of Pathology. The specimens included 99 cases of endobronchial ultrasound-guided (EBUS) fine-needle aspiration (FNA), 67 cases of computed tomography (CT)-guided FNA, 27 cases of body fluid, 10 cases of ultrasound-guided of superficial FNA, and 6 cases of other cytology specimens. DNA sequencing for EGFR exons 18-21 and KRAS codons 12, 13, and 61 was performed. The overall specimen insufficiency rate was low (6.2%). EBUS (4%) and body-fluid cases (3.7%) showed lower insufficiency rates than the other cases. Similar insufficiency rates were observed in smears (6.1%) and cell-block sections (6.4%). EGFR mutations were detected in 19.4% (34 of 175) of nonsmall cell lung carcinoma (NSCLC) with a significantly higher frequency in adenocarcinoma (29%, 29 of 100) than in nonadenocarcinoma (7%, 5 of 75, P = .002). KRAS mutations were detected in 23.6% (41 of 174) of NSCLCs with no statistical differences between adenocarcinoma (26%, 26 of 102) and nonadenocarcinoma (21%, 17 of 72, P = .86). Higher frequencies of EGFR mutations in exons 19 and 21 (65%) than in exons 18 and 20 were detected. Our findings support clinical utilization of routinely prepared cytology specimens, including EBUS, CT/US. FNAs and body fluid specimens, as a reliable source for molecular testing to detect EGFR or KRAS mutations in patients with NSCLC. Copyright © 2011 American Cancer Society.

  14. Trichomonas vaginalis induces cytopathic effect on human lung alveolar basal carcinoma epithelial cell line A549.

    PubMed

    Salvador-Membreve, Daile Meek C; Jacinto, Sonia D; Rivera, Windell L

    2014-12-01

    Trichomonas vaginalis, the causative agent of trichomoniasis is generally known to inhabit the genitourinary tract. However, several case reports with supporting molecular and immunological identifications have documented its occurrence in the respiratory tract of neonates and adults. In addition, the reports have documented that its occurrence is associated with respiratory failures. The medical significance or consequence of this association is unclear. Thus, to establish the possible outcome from the interaction of T. vaginalis with lung cells, the cytopathic effects of the parasites were evaluated using monolayer cultures of the human lung alveolar basal carcinoma epithelial cell line A549. The possible effect of association of T. vaginalis with A549 epithelial cells was analyzed using phase-contrast, scanning electron microscopy and fluorescence microscopy. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), crystal-violet and TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP nick-end labelling) assays were conducted for cytotoxicity testing. The results demonstrate that T. vaginalis: (1) adheres to A549 epithelial cells, suggesting a density-dependent parasite-cell association; (2) adherence on A549 is through flagella, membrane and axostyle; (3) causes cell detachment and cytotoxicity (50-72.4%) to A549 and this effect is a function of parasite density; and (4) induces apoptosis in A549 about 20% after 6 h of incubation. These observations indicate that T. vaginalis causes cytopathic effects on A549 cell. To date, this is the first report showing a possible interaction of T. vaginalis with the lung cells using A549 monolayer cultures. Further studies are recommended to completely elucidate this association.

  15. FoxO6 inhibits cell proliferation in lung carcinoma through up-regulation of USP7.

    PubMed

    Hu, Hong-Jun; Zhang, Li-Guo; Wang, Zhen-Hua; Guo, Xi-Xi

    2015-07-01

    Emerging evidence has suggested that misregulation of oncogenes and/or tumor suppressors has a crucial role in the development of lung carcinoma. The present study demonstrated that the expression levels of forkhead box O6 (FOXO6) were downregulated in lung cancer tissue samples, as compared with those in adjacent normal tissue. Overexpression of FOXO6 inhibited the proliferation of A549 human lung cancer cells, whereas knockdown of endogenous FOXO6 expression enhanced cell proliferation. Furthermore, ectopic FOXO6 expression induced the expression of ubiquitin-specific-processing protease 7 (USP7). As a result of this regulation, FOXO6 overexpression led to an elevation of p53 protein expression levels in A549 cells. In conclusion, the results of the present study indicated that the FOXO6/USP7 molecular network has an important role in the regulation of lung cancer development.

  16. Urinary metabolomic study of non-small cell lung carcinoma based on ultra high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry.

    PubMed

    Wu, Qian; Wang, Yan; Gu, Xue; Zhou, Junyi; Zhang, Huiping; Lv, Wang; Chen, Zhe; Yan, Chao

    2014-07-01

    Metabolic profiles from human urine reveal the significant difference of carnitine and acylcarnitines levels between non-small cell lung carcinoma patients and healthy controls. Urine samples from cancer patients and healthy individuals were assayed in this metabolomic study using ultra high performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. The data were normalized by the sum of all intensities and creatinine calibration, respectively, before orthogonal partial least squares discriminant analysis. Twenty differential metabolites were identified based on standard compounds or tandem mass spectrometry fragments. Among them, some medium-/long-chain acylcarnitines, for example, cis-3,4-methylene heptanoylcarnitine, were found to be downregulated while carnitine was upregulated in urine samples from the cancer group compared to the control group. Receiver operating characteristic analysis of the two groups showed that the area under curve for the combination of carnitine and 11 selected acylcarnitines was 0.958. This study suggests that the developed carnitine and acylcarnitines profiling method has the potential to be used for screening non-small cell lung carcinoma.

  17. 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

  18. High-resolution CT findings of primary lung cancer with cavitation: a comparison between adenocarcinoma and squamous cell carcinoma.

    PubMed

    Kunihiro, Y; Kobayashi, T; Tanaka, N; Matsumoto, T; Okada, M; Kamiya, M; Ueda, K; Kawano, H; Matsunaga, N

    2016-11-01

    To evaluate the high-resolution computed tomography (CT) findings of primary lung cancer with cavitation and compare the findings in adenocarcinoma and squamous cell carcinoma. The high-resolution CT findings of tumours with cavitation were retrospectively evaluated in 60 patients. Forty-seven of the lesions were diagnosed as adenocarcinomas; 13 were diagnosed as squamous cell carcinomas. The diameters of the tumour and cavity, the maximum thickness of the cavity wall, shape of the cavity wall, the number of cavities, and the presence of ground-glass opacity, bronchial obstruction, intratumoural bronchiectasis, emphysema, and honeycombing were evaluated. The mechanisms of cavity formation were examined according to the pathological features. The maximum thickness of the cavity wall was significantly greater in squamous cell carcinomas than in adenocarcinomas (p=0.002). Ground-glass opacity and intratumoural bronchiectasis were significantly more common in adenocarcinomas than in squamous cell carcinomas (p<0.001 and p=0.040, respectively). Regarding the pathological findings, intratumoural bronchiectasis with or without alveolar wall destruction contributed to a significant difference between adenocarcinoma and squamous cell carcinoma (p<0.001; odds ratio [OR], 20.35; 95% confidence interval [CI], 3.87-107.10). The cavity wall tends to be thicker in squamous cell carcinomas than in adenocarcinomas. The presence of ground-glass opacity and intratumoural bronchiectasis is strongly suggestive of adenocarcinoma. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  19. Urine and bladder washing cytology for detection of urothelial carcinoma: standard test with new possibilities

    PubMed Central

    Flezar, Margareta Strojan

    2010-01-01

    Background Light microscopic evaluation of cell morphology in preparations from urine or bladder washing containing exfoliated cells is a standard and primary method for the detection of bladder cancer and also malignancy from other parts of the urinary tract. The cytopathologic examination is a valuable method to detect an early recurrence of malignancy or new primary carcinoma during the follow-up of patients after the treatment of bladder cancer. Conclusions Characteristic cellular and nuclear signs of malignancy indicate invasive or in situ urothelial carcinoma or high-grade papillary urothelial carcinoma. However, low sensitivity of the method reflects the unreliable cytopathologic diagnosis of low-grade urothelial neoplasms as cellular and nuclear signs of malignancy in these neoplasms are poorly manifested. Many different markers were developed to improve the diagnosis of bladder carcinoma on urinary samples. UroVysion™ test is among the newest and most promising tests. By the method of in situ hybridization one can detect specific cytogenetic changes of urothelial carcinoma. PMID:22933917

  20. Radiation enhanced efficiency of combined electromagnetic hyperthermia and chemotherapy of lung carcinoma using cisplatin functionalized magnetic nanoparticles.

    PubMed

    Babincová, M; Kontrisova, K; Durdík, S; Bergemann, C; Sourivong, P

    2014-02-01

    The effect of trimodality treatment consisting of hyperthermia, cisplatin and radiation was investigated in two non-small lung carcinoma cell lines with different sensitivities to cisplatin. Hyperthermia treatment was performed using heat released via Neél and Brown relaxation of magnetic nanoparticles in an alternating magnetic field. Radiation with dose 1.5 Gy was performed after 15 min electromagnetic hyperthermia and cisplatin treatment. Electromagnetic hyperthermia enhanced cisplatin-induced radiosensitization in both the cisplatin-sensitive H460 (viability 11.2 +/- 1.8 %) and cisplatin-resistant A549 (viability 14.5 +/- 2.3 %) lung carcinoma cell line. Proposed nanotechnology based trimodality cancer treatment may have therefore important clinical applications.

  1. Evaluation of the Feasibility of Screening Patients for Early Signs of Lung Carcinoma in Web Search Logs.

    PubMed

    White, Ryen W; Horvitz, Eric

    2017-03-01

    A statistical model that predicts the appearance of strong evidence of a lung carcinoma diagnosis via analysis of large-scale anonymized logs of web search queries from millions of people across the United States. To evaluate the feasibility of screening patients at risk of lung carcinoma via analysis of signals from online search activity. We identified people who issue special queries that provide strong evidence of a recent diagnosis of lung carcinoma. We then considered patterns of symptoms expressed as searches about concerning symptoms over several months prior to the appearance of the landmark web queries. We built statistical classifiers that predict the future appearance of landmark queries based on the search log signals. This was a retrospective log analysis of the online activity of millions of web searchers seeking health-related information online. Of web searchers who queried for symptoms related to lung carcinoma, some (n = 5443 of 4 813 985) later issued queries that provide strong evidence of recent clinical diagnosis of lung carcinoma and are regarded as positive cases in our analysis. Additional evidence on the reliability of these queries as representing clinical diagnoses is based on the significant increase in follow-on searches for treatments and medications for these searchers and on the correlation between lung carcinoma incidence rates and our log-based statistics. The remaining symptom searchers (n = 4 808 542) are regarded as negative cases. Performance of the statistical model for early detection from online search behavior, for different lead times, different sets of signals, and different cohorts of searchers stratified by potential risk. The statistical classifier predicting the future appearance of landmark web queries based on search log signals identified searchers who later input queries consistent with a lung carcinoma diagnosis, with a true-positive rate ranging from 3% to 57% for false-positive rates ranging

  2. Effect of Allium sativum (garlic) diallyl disulfide (DADS) on human non-small cell lung carcinoma H1299 cells.

    PubMed

    Hui, C; Jun, W; Ya, L N; Ming, X

    2008-04-01

    This study was undertaken to elucidate the effect of diallyl disulfide from Allium sativum, an oil-soluble organosulfur compound found in garlic, in suppressing human non-small cell lung carcinoma H1299 cells. A potent increase in apoptotic cells has accompanied 1) a decrease in cell viability, 2) an increase of the fraction of G2/M-phase cells by up to 48.80 %, and 3) a transient increase of the phospho-p42/44 (phosphorylated p42/44 MAPK) in a time- and concentration-dependent manner. These results indicated that diallyl disulfide could induce apoptosis in human non-small cell lung carcinoma H1299 cells via, at least partly, G2/M-phase block of the cell cycle, related to a rise in MAPK phosphorylation.

  3. Development of Marjolin's ulcer within one month of burn injury with synchronous primary lung squamous cell carcinoma in an elderly patient: report of a case with allelotyping.

    PubMed

    Wooldridge, Adam N; Griesser, Michael J; Scharschmidt, Thomas; Iwenofu, O Hans

    2011-12-01

    Marjolin's ulcer defines the occurrence of malignancy, usually squamous cell carcinoma, in the setting of a post-traumatic scar often following thermal injury. The latency period from the time of injury to the onset of malignant transformation averages 30 years with the earliest documented incidence occurring 6 weeks after injury. In addition, the occurrence of multiple primary malignancies is a rare event. To our knowledge, we report the first case in the literature of a well-differentiated squamous cell carcinoma developing within 1 month of thermal injury to an elderly patient's right index finger with an incidental synchronous primary lung moderately differentiated squamous cell carcinoma that was morphologically and genetically different as confirmed by allelotyping. There is scant precedent literature on acute Marjolin's ulcers, and the most acute cases have arisen 6 weeks post-burn. There is also little published literature on the incidence of multiple primary malignancies. The quoted incidence of this event is <1%. Clinicians should be aware of the possibility of malignant transformation at the site of prior thermal injury. Biopsy remains the gold standard for diagnosis for Marjolin's ulcer. MRI is the most important diagnostic imaging tool because it will demonstrate the margins and extent of the lesion. Due to the aggressive nature of Marjolin's ulcer, treatment is usually surgical and dependent upon grading. When multiple lesions are detected after staging of a presumed neoplasm, the possibility of multiple primary maligancies should be considered. Allelotyping is a process that can be utilized to determine if multiple masses are related.

  4. Large cell neuroendocrine carcinoma of the lung: CT and FDG PET findings.

    PubMed

    Lee, Kyung Won; Lee, Youkyung; Oh, So Won; Jin, Kwang Nam; Goo, Jin Mo

    2015-11-01

    To evaluate the CT and (18)fluorine FDG PET findings of large cell neuroendocrine carcinomas (LCNECs) of the lung and to evaluate whether CT and FDG PET findings can help predict the clinical outcome. Thirty-one patients (Male:Female=29:2; mean age, 69 years) who underwent surgical resection of an LCNEC of the lung were included in this retrospective study. The tumours were assessed with respect to morphologic characteristics and the maximum standardised uptake value (SUVmax) on pre-operative CT and FDG PET. For patients undergoing curative resection (n=26), disease-free survival was evaluated using the Kaplan-Meier test. The prognostic significance was assessed using a multivariate Cox proportional hazards regression analysis. The mean tumour diameter was 3.8 ± 2.1cm. Eight tumours (25.8%) were located centrally in the lung, and 23 (74.2%) were located peripherally. The margins were lobulated in 29 patients (93.5%) and well defined in 20 (64.5%). The mean SUVmax was 9.0 ± 3.8. The five-year disease-free survival rate was 46.3%. The shorter disease-free survival was related to the TNM stage greater than stage I, no lobulated margin of a tumour, a SUVmax >12.9 of a tumour, a long diameter >5.6 cm of a tumour, or female gender (P=0.115, P=0.134, P=0.056, P=0.168, P=0.113, respectively). The multivariate analysis indicated that a long diameter >5.6 cm (hazard ratio, 9.265; 90% confidence interval (CI), 1.996-42.992; P=0.017), female gender (hazard ratio, 5.579; 90% CI, 1.398-22.264; P=0.041), no lobulated margin (hazard ratio, 9.955; 90% CI, 1.433-69.136; P=0.051), and SUVmax >12.9 (hazard ratio, 4.062; 90% CI, 1.235-13.368; P=0.053) were independent predictors of shorter disease-free survival. LCNECs of the lung more commonly occurred peripherally and exhibited well-defined and lobulated margins on CT. The mean SUVmax was consistent with malignant tumours. Female gender, a larger tumour diameter, no lobulated margin, and higher SUVmax were poor prognostic

  5. Mitochondrial dysfunction is an essential step for killing of non-small cell lung carcinomas resistant to conventional treatment.

    PubMed

    Joseph, Bertrand; Marchetti, Philippe; Formstecher, Pierre; Kroemer, Guido; Lewensohn, Rolf; Zhivotovsky, Boris

    2002-01-03

    Apoptosis, a tightly controlled multi-step mechanism of cell death, is important for anti-cancer therapy-based elimination of tumor cells. However, this process is not always efficient. Small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC) cells display different susceptibility to undergo apoptosis induced by anticancer treatment. In contrast to SCLC, NSCLC cells are cross-resistant to a broad spectrum of apoptotic stimuli, including receptor stimulation, cytotoxic drugs and gamma-radiation. Since resistance of tumor cells to treatment often accounts for the failure of traditional forms of cancer therapy, in the present study attempts to find a potent broad-range apoptosis inductor, which can kill therapy-resistant NSCLC cells were undertaken and the mechanism of apoptosis induction by this drug was investigated in detail. We found that staurosporine (STS) had cell killing effect on both types of lung carcinomas. Release of cytochrome c, activation of apical and effector caspases followed by cleavage of their nuclear substrates and morphological changes specific for apoptosis were observed in STS-treated cells. In contrast to treatment with radiation or chemotherapy drugs, STS induces mitochondrial dysfunction followed by translocation of AIF into the nuclei. These events preceded the activation of nuclear apoptosis. Thus, in lung carcinomas two cell death pathways, caspase-dependent and caspase-independent, coexist. In NSCLC cells, where the caspase-dependent pathway is less efficient, the triggering of an AIF-mediated caspase-independent mechanism circumvents the resistance of these cells to treatment.

  6. Erlotinib pretreatment improves photodynamic therapy of non-small cell lung carcinoma xenografts via multiple mechanisms

    PubMed Central

    Gallagher-Colombo, Shannon M.; Miller, Joann; Cengel, Keith A.; Putt, Mary E.; Vinogradov, Sergei A.; Busch, Theresa M.

    2015-01-01

    Aberrant expression of the epidermal growth factor receptor (EGFR) is a common characteristic of many cancers including non-small cell lung carcinoma (NSCLC), head and neck squamous cell carcinoma, and ovarian cancer. While EGFR is currently a favorite molecular target for treatment of these cancers, inhibition of the receptor with small molecule inhibitors (i.e.- erlotinib) or monoclonal antibodies (i.e.- cetuximab) does not provide long-term therapeutic benefit as standalone treatment. Interestingly, we have found that addition of erlotinib to photodynamic therapy (PDT) can improve treatment response in typically erlotinib-resistant NSCLC tumor xenografts. Ninety-day complete response rates of 63% are achieved when erlotinib is administered in three doses before PDT of H460 human tumor xenografts, compared to 16% after PDT-alone. Similar benefit is found when erlotinib is added to PDT of A549 NCSLC xenografts. Improved response is accompanied by increased vascular shutdown, and erlotinib increases the in vitro cytotoxicity of PDT to endothelial cells. Tumor uptake of the photosensitizer (benzoporphyrin derivative monoacid ring A; BPD) is increased by the in vivo administration of erlotinib; nevertheless, this elevation of BPD levels only partially accounts for the benefit of erlotinib to PDT. Thus, pretreatment with erlotinib augments multiple mechanisms of PDT effect that collectively lead to large improvements in therapeutic efficacy. These data demonstrate that short-duration administration of erlotinib before PDT can greatly improve the responsiveness of even erlotinib-resistant tumors to treatment. Results will inform clinical investigation of EGFR-targeting therapeutics in conjunction with PDT. PMID:26054596

  7. Apoptosis and cell cycle disturbances induced by coumarin and 7-hydroxycoumarin on human lung carcinoma cell lines.

    PubMed

    Lopez-Gonzalez, Jose Sullivan; Prado-Garcia, Heriberto; Aguilar-Cazares, Dolores; Molina-Guarneros, Juan A; Morales-Fuentes, Jorge; Mandoki, Juan Jose

    2004-03-01

    Coumarin and 7-hydroxycoumarin have anti-tumour actions in vitro and in vivo. There are no previous reports on the cytostatic and apoptotic actions of coumarin and 7-hydroxycoumarin in non-small cell lung carcinoma (NSCLC) cell lines. Here we report on: (1) the inhibition of cell proliferation, (2) the phase in which cell cycle arrest occurs, and (3) the induction of apoptosis. Inhibition of cell proliferation was determined by 3H-thymidine incorporation. The effects on cell cycle phases were determined at 100 microg/ml of coumarin or 7-hydroxycoumarin using propidium iodide and flow cytometry. Higher concentrations were used to study apoptosis, detected by: (1) morphological cell changes, (2) subG1 peak detection and (3) Annexin-V assay. Peripheral blood mononuclear cells (PBMC) stimulated with phytohemagglutinin were used as controls. The actions of these compounds depended on drug concentrations and on histological cell type. Coumarin and 7-hydroxycoumarin inhibited cell growth by inducing cell cycle arrest in the G1 phase in all the lung carcinoma cell lines. Apoptosis required large concentrations of the coumarin compounds and was observed in adenocarcinomas. Apoptosis was not associated with intra-nucleosomal DNA fragmentation. Apoptosis was not observed in squamous lung carcinoma cell lines, but an increase in G1 cell cycle arrest was detected. In PBMC, only large concentrations of the coumarin compounds elicited a cystostatic action. Coumarins in combination with other anti-neoplastic drugs might increase the effectiveness of NSCLC treatments.

  8. Longitudinally Extensive Transverse Myelitis with Intramedullary Metastasis of Small-Cell Lung Carcinoma: An Autopsy Case Report

    PubMed Central

    Tanaka, Ryota; Tsutsumi, Satoshi; Oji, Yutaka; Saeki, Harumi; Yasumoto, Yukimasa; Ito, Masanori; Hattori, Nobutaka; Urabe, Takao

    2013-01-01

    Background. Longitudinally extensive transverse myelitis (LETM) is characterized by spinal cord inflammation extending vertically through three or more vertebral segments. The widespread use of MRI revealed LETM more frequency than ever. We report the case of a patient with pathologically confirmed small-cell lung carcinoma metastasis into the spinal cord presenting as LETM. Case Presentation. A 74-year-old man developed rapidly progressive sensorimotor disturbance and vesicorectal dysfunction. T2-weighted magnetic resonance imaging of the spine revealed LETM at the level of from T3 to conus medullaris; gadolinium enhancement showed concurrent tumor in the thoracic spinal cord from T10 to T11. Systemic survey identified a nodular mass in the lung that was verified as small-cell carcinoma. Following initial failed treatment by high-dose steroid, the patient underwent an emergent microsurgical tumor resection. Histological examination was identical with the lung carcinoma. The patient died of tumor progression at the 47th day after admission. At autopsy, only changes of edema were found in the gray matter of the cord, while tumor cells were not noted in it. Conclusion. Metastasis may rarely present symptoms of LETM. Prompt identification of underlying etiology by contrast examination and systemic survey is crucial for the patient assumed as LETM. PMID:24455343

  9. COPD increases the risk of squamous histological subtype in smokers who develop non-small cell lung carcinoma

    PubMed Central

    Papi, A; Casoni, G; Caramori, G; Guzzinati, I; Boschetto, P; Ravenna, F; Calia, N; Petruzzelli, S; Corbetta, L; Cavallesco, G; Forini, E; Saetta, M; Ciaccia, A; Fabbri, L

    2004-01-01

    Background: Squamous cell carcinoma has a stronger association with tobacco smoking than other non-small cell lung cancers (NSCLC). A study was undertaken to determine whether chronic obstructive pulmonary disease (COPD) is a risk factor for the squamous cell carcinoma histological subtype in smokers with surgically resectable NSCLC. Methods: Using a case-control design, subjects with a surgically confirmed diagnosis of squamous cell carcinoma were enrolled from smokers undergoing lung resection for NSCLC in the District Hospital of Ferrara, Italy. Control subjects were smokers who underwent lung resection for NSCLC in the same hospital and had a surgically confirmed diagnosis of NSCLC of any histological type other than squamous cell. Results: Eighty six cases and 54 controls (mainly adenocarcinoma, n = 50) were enrolled. The presence of COPD was found to increase the risk for the squamous cell histological subtype by more than four times. Conversely, the presence of chronic bronchitis was found to decrease the risk for this histological subtype by more than four times. Among patients with chronic bronchitis (n = 77), those with COPD had a 3.5 times higher risk of having the squamous cell histological subtype. Conclusions: These data suggest that, among smokers with surgically resectable NSCLC, COPD is a risk factor for the squamous cell histological subtype and chronic bronchitis, particularly when not associated with COPD, is a risk factor for the adenocarcinoma histological subtype. PMID:15282388

  10. Protein kinase C involvement in aloe-emodin- and emodin-induced apoptosis in lung carcinoma cell.

    PubMed

    Lee, H Z

    2001-11-01

    1. This study demonstrated aloe-emodin- and emodin-induced apoptosis in lung carcinoma cell lines CH27 (human lung squamous carcinoma cell) and H460 (human lung non-small cell carcinoma cell). Aloe-emodin- and emodin-induced apoptosis was characterized by nuclear morphological changes and DNA fragmentation. 2. During apoptosis, an increase in cytochrome c of cytosolic fraction and activation of caspase-3, identified by the cleavage of its proform, were observed. 3. To elucidate whether the expression of protein kinase C (PKC) isozymes are involved in aloe-emodin- and emodin-induced apoptosis, this study examined the changes of PKC isozymes by Western blotting techniques during aloe-emodin- and emodin-induced apoptosis. 4. The expression of PKC isozymes involved in aloe-emodin- and emodin-induced apoptosis of CH27 and H460 cells. In this study, aloe-emodin and emodin induced the changes of each of PKC isozymes in CH27 and H460 cells. 5. The decrease in the expression of PKC delta and epsilon may play a critical role in aloe-emodin- and emodin-induced apoptosis in CH27 and H460 cells. 6. The present study also demonstrated that PKC stimulation occurs at a site downstream of caspase-3 in the emodin-mediated apoptotic pathway.

  11. Pulmonary CYP2A13 levels are associated with early occurrence of lung cancer-Its implication in mutagenesis of non-small cell lung carcinoma.

    PubMed

    Chiang, Huai-Chih; Lee, Huei; Chao, How-Ran; Chiou, Yu-Hu; Tsou, Tsui-Chun

    2013-10-01

    CYP2A13, a human pulmonary specific cytochrome P450 enzyme, plays an important role in susceptibility to tobacco-specific nitrosamines (TSNAs)-induced lung cancer in humans. The pattern of CYP2A13 distribution in respiratory tract affects the susceptibility of the lung to carcinogens. CYP2A13 is expressed in the epithelium of trachea and bronchi; however its pattern of expression in human lung cancer remains largely unknown. This study aimed to determine the CYP2A13 expression in specimens from human non-small cell lung carcinomas (NSCLCs), i.e., adenocarcinoma and squamous carcinoma, by immunohistochemical (IHC) analysis and to identify the potential linkage between tumor CYP2A13 levels and some clinicopathological characteristics of NSCLC patients in Taiwan. The tumor CYP2A13 IHC staining signal was strong in 76% of the 112 study subjects. Study subjects (especially non-smoking or lung adenocarcinoma patients) with higher tumor CYP2A13 levels were younger. Multiple logistic regression analysis revealed that in younger subjects (age ≤ 66) and heavy smokers (pack-years ≥ 40), the odds ratio (OR) for positive tumor CYP2A13 staining was significantly higher than that for negative tumor CYP2A13 staining. Moreover, the association of EGFR gene mutations and positive tumor CYP2A13 staining was also revealed. In conclusion, these findings suggest the potential involvement of pulmonary CYP2A13 in the early occurrence of NSCLC as well as in the development of EGFR gene mutations.

  12. 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

    2017-04-03

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

  13. Prognostic value of LIPC in non-small cell lung carcinoma

    PubMed Central

    Galluzzi, Lorenzo; Goubar, Aicha; Olaussen, Ken André; Vitale, Ilio; Senovilla, Laura; Michels, Judith; Robin, Angélique; Dorvault, Nicolas; Besse, Benjamin; Validire, Pierre; Fouret, Pierre; Behrens, Carmen; Wistuba, Ignacio Ivan; Soria, Jean-Charles; Kroemer, Guido

    2013-01-01

    Non-small cell lung carcinoma (NSCLC) is the most common form of lung cancer and is associated with a high mortality rate worldwide. The majority of individuals bearing NSCLC are treated with surgery plus adjuvant cisplatin, an initially effective therapeutic regimen that, however, is unable to prevent relapse within 5 years after tumor resection in an elevated proportion of patients. The factors that predict the clinical course of NSCLC and its sensitivity to therapy remain largely obscure. One notable exception is provided by pyridoxal kinase (PDXK), the enzyme that generates the bioactive form of vitamin B6. PDXK has recently been shown to be required for optimal cisplatin responses in vitro and in vivo and to constitute a bona fide prognostic marker in the NSCLC setting. Together with PDXK, 84 additional factors were identified that influence the response of NSCLC cells to cisplatin, in vitro including the hepatic lipase LIPC. Here, we report that the intratumoral levels of LIPC, as assessed by immunohistochemistry in two independent cohorts of NSCLC patients, positively correlate with disease outcome. In one out of two cohorts studied, the overall survival of NSCLC patients bearing LIPChigh lesions was unaffected, if not slightly worsened, by cisplatin-based adjuvant therapy. Conversely, the overall survival of patients with LIPClow lesions was prolonged by post-operative cisplatin. Pending validation in appropriate clinical series, these results suggest that LIPClow NSCLC patients would be those who mainly benefit from adjuvant cisplatin therapy. Thus, the expression levels of LIPC appear to have an independent prognostic value (and perhaps a predictive potential) in the setting of NSCLC. If these findings were confirmed by additional studies, LIPC expression levels might allow not only for NSCLC patient stratification, but also for the implementation of personalized therapeutic approaches. PMID:23343765

  14. FGFR gene alterations in lung squamous cell carcinoma are potential targets for the multikinase inhibitor nintedanib.

    PubMed

    Hibi, Masaaki; Kaneda, Hiroyasu; Tanizaki, Junko; Sakai, Kazuko; Togashi, Yosuke; Terashima, Masato; De Velasco, Marco Antonio; Fujita, Yoshihiko; Banno, Eri; Nakamura, Yu; Takeda, Masayuki; Ito, Akihiko; Mitsudomi, Tetsuya; Nakagawa, Kazuhiko; Okamoto, Isamu; Nishio, Kazuto

    2016-11-01

    Fibroblast growth factor receptor (FGFR) gene alterations are relatively frequent in lung squamous cell carcinoma (LSCC) and are a potential targets for therapy with FGFR inhibitors. However, little is known regarding the clinicopathologic features associated with FGFR alterations. The angiokinase inhibitor nintedanib has shown promising activity in clinical trials for non-small cell lung cancer. We have now applied next-generation sequencing (NGS) to characterize FGFR alterations in LSCC patients as well as examined the antitumor activity of nintedanib in LSCC cell lines positive for FGFR1 copy number gain (CNG). The effects of nintedanib on the proliferation of and FGFR signaling in LSCC cell lines were examined in vitro, and its effects on tumor formation were examined in vivo. A total of 75 clinical LSCC specimens were screened for FGFR alterations by NGS. Nintedanib inhibited the proliferation of FGFR1 CNG-positive LSCC cell lines in association with attenuation of the FGFR1-ERK signaling pathway in vitro and in vivo. FGFR1 CNG (10.7%), FGFR1 mutation (2.7%), FGFR2 mutation (2.7%), FGFR4 mutation (5.3%), and FGFR3 fusion (1.3%) were detected in LSCC specimens by NGS. Clinicopathologic features did not differ between LSCC patients positive or negative for FGFR alterations. However, among the 36 patients with disease recurrence after surgery, prognosis was significantly worse for those harboring FGFR alterations. Screening for FGFR alterations by NGS warrants further study as a means to identify patients with LSCC recurrence after surgery who might benefit from nintedanib therapy.

  15. 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.

  16. Fucoidan from Undaria pinnatifida induces apoptosis in A549 human lung carcinoma cells.

    PubMed

    Boo, Hye-Jin; Hyun, Jae-Hee; Kim, Sang-Cheol; Kang, Jung-Il; Kim, Min-Kyoung; Kim, Sun-Yeou; Cho, Heeyeong; Yoo, Eun-Sook; Kang, Hee-Kyoung

    2011-07-01

    Fucoidan, a sulfated polysaccharide, has various biological activities, such as anticancer, antiangiogenic and antiinflammatory effects; however, the mechanisms of action of fucoidan on anticancer activity have not been fully elucidated. The anticancer effects of fucoidan from Undaria pinnatifida on A549 human lung carcinoma cells were examined. Treatment of A549 cells with fucoidan resulted in potent antiproliferative activity. Also, some typical apoptotic characteristics, such as chromatin condensation and an increase in the population of sub-G1 hypodiploid cells, were observed. With respect to the mechanism underlying the induction of apoptosis, fucoidan reduced Bcl-2 expression, but the expression of Bax was increased in a dose-dependent manner compared with the controls. Furthermore, fucoidan induced caspase-9 activation, but decreased the level of procaspase-3. Cleavage of poly-ADP-ribose polymerase (PARP), a vital substrate of effector caspase, was found. The study further investigated the role of the MAPK and PI3K/Akt pathways with respect to the apoptotic effect of fucoidan, and showed that fucoidan activates ERK1/2 in A549 cells. Unlike ERK1/2, however, treatment with fucoidan resulted in the down-regulation of phospho-p38 expression. In addition, fucoidan resulted in the down-regulation of phospho-PI3K/Akt. Together, these results indicate that fucoidan induces apoptosis of A549 human lung cancer cells through down-regulation of p38, PI3K/Akt, and the activation of the ERK1/2 MAPK pathway.

  17. 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.

  18. Large Cell Neuroendocrine Carcinoma of the Lung: Clinico-Pathologic Features, Treatment, and Outcomes.

    PubMed

    Naidoo, Jarushka; Santos-Zabala, Maria L; Iyriboz, Tunc; Woo, Kaitlin M; Sima, Camelia S; Fiore, John J; Kris, Mark G; Riely, Gregory J; Lito, Piro; Iqbal, Afsheen; Veach, Stephen; Smith-Marrone, Stephanie; Sarkaria, Inderpal S; Krug, Lee M; Rudin, Charles M; Travis, William D; Rekhtman, Natasha; Pietanza, Maria C

    2016-09-01

    Large cell neuroendocrine carcinoma (LCNEC) accounts for approximately 3% of lung cancers. Pathologic classification and optimal therapies are debated. We report the clinicopathologic features, treatment and survival of a series of patients with stage IV LCNEC. Cases of pathologically-confirmed stage IV LCNEC evaluated at Memorial Sloan Kettering Cancer Center from 2006 to 2013 were identified. We collected demographic, treatment, and survival data. Available radiology was evaluated by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria. Forty-nine patients with stage IV LCNEC were identified. The median age was 64 years, 63% of patients were male, and 88% were smokers. Twenty-three patients (n = 23/49; 47%) had brain metastases, 17 at diagnosis and 6 during the disease course. Seventeen LCNEC patients (35%) had molecular testing, of which 24% had KRAS mutations (n = 4/17). Treatment data for first-line metastatic disease was available on 37 patients: 70% (n = 26) received platinum/etoposide and 30% (n = 11) received other regimens. RECIST was completed on 23 patients with available imaging; objective response rate was 37% (95% confidence interval, 16%-62%) with platinum/etoposide, while those treated with other first-line regimens did not achieve a response. Median overall survival was 10.2 months (95% confidence interval, 8.6-16.4 months) for the entire cohort. Patients with stage IV LCNEC have a high incidence of brain metastases. KRAS mutations are common. Patients with stage IV LCNEC do not respond as well to platinum/etoposide compared with historic data for extensive stage small-cell lung cancer; however, the prognosis is similar. Prospective studies are needed to define optimum therapy for stage IV LCNEC. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Does periodic lung screening of films meets standards?

    PubMed Central

    Binay, Songul; Arbak, Peri; Safak, Alp Alper; Balbay, Ege Gulec; Bilgin, Cahit; Karatas, Naciye

    2016-01-01

    Objective: To determine whether the workers’ periodic chest x-ray screening techniques in accordance with the quality standards is the responsibility of physicians. Evaluation of differences of interpretations by physicians in different levels of education and the importance of standardization of interpretation. Methods: Previously taken chest radiographs of 400 workers who are working in a factory producing the glass run channels were evaluated according to technical and quality standards by three observers (pulmonologist, radiologist, pulmonologist assistant). There was a perfect concordance between radiologist and pulmonologist for the underpenetrated films. Whereas there was perfect concordance between pulmonologist and pulmonologist assistant for over penetrated films. Results: Pulmonologist (52%) has interpreted the dose of the films as regular more than other observers (radiologist; 44.3%, pulmonologist assistant; 30.4%). The frequency of interpretation of the films as taken in inspiratory phase by the pulmonologist (81.7%) was less than other observers (radiologist; 92.1%, pulmonologist assistant; 92.6%). The rate of the pulmonologist (53.5%) was higher than the other observers (radiologist; 44.6%, pulmonologist assistant; 41.8%) for the assessment of the positioning of the patients as symmetrical. Pulmonologist assistant (15.3%) was the one who most commonly reported the parenchymal findings (radiologist; 2.2%, pulmonologist; 12.9%). Conclusion: It is necessary to reorganize the technical standards and exposure procedures for improving the quality of the chest radiographs. The reappraisal of all interpreters and continuous training of technicians is required. PMID:28083054

  20. 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.

  1. Squamous cell carcinoma of pancreas: an unusual site of relapse from early-stage lung cancer: 12-month postsurgery

    PubMed Central

    Sharma, Anand; Alfa-Wali, Maryam; Rodriguez-Justo, Manuel; Polychronis, Andreas

    2013-01-01

    A 57-year-old man presented with abdominal pain and backache, weight loss of 10 kg and irregular bowel movements. He was previously diagnosed with Stage IB squamous cell carcinoma of lung and had undergone lobectomy 12 months previously. Investigations including imaging revealed a cystic mass in the body and tail of the pancreas which was biopsied and it was confirmed to be a recurrence of the squamous lung cancer involving the pancreas. He was treated with systemic chemotherapy and has shown a partial response on repeat imaging. This case illustrates a rare and unusual site of relapse in lung cancer after adjuvant therapy and a key message for follow-up surveillance for these patients. PMID:23608858

  2. Iron deficiency anemia as initial presentation of a non-small cell lung carcinoma: A case report

    PubMed Central

    Linsen, Philip V.M.; Linsen, Victor M.J.; Buunk, Gerba; Arnold, Dorothee E.; Aerts, Joachim G.J.V.

    2015-01-01

    Duodenal metastases secondary to lung cancer are very rare and most of the time asymptomatic. When symptomatic they usually present with bowel obstruction or perforation. We here describe the case of a 68 year-old man with a solitary metastasis in the duodenum from a non-small cell lung carcinoma (NSCLC). The patient presented with reduced exercise tolerance and iron deficiency anemia without clinical gastrointestinal blood loss. Further investigation showed a tumor in the left upper lung lobe and a duodenal metastasis for which he received chemotherapy. To the best of our knowledge this is the first case report of iron deficiency anemia as initial presentation of a duodenal metastasis from a NSCLC. PMID:26744672

  3. The Calcium-Sensing Receptor Is Necessary for the Rapid Development of Hypercalcemia in Human Lung Squamous Cell Carcinoma12

    PubMed Central

    Lorch, Gwendolen; Viatchenko-Karpinski, Serge; Ho, Hsiang-Ting; Dirksen, Wessel P; Toribio, Ramiro E; Foley, John; Györke, Sandor; Rosol, Thomas J

    2011-01-01

    The calcium-sensing receptor (CaR) is responsible for the regulation of extracellular calcium (Ca2+o) homeostasis. CaR activation has been shown to increase proliferation in several cancer cell lines; however, its presence or function has never been documented in lung cancer. We report that Ca2+o-activated CaR results in MAPK-mediated stimulation of parathyroid hormone-related protein (PTHrP) production in human lung squamous cell carcinoma (SCC) lines and humoral hypercalcemia of malignancy (HHM) in vivo. Furthermore, a single nucleotide polymorphism in CaR identified from a hypercalcemia-inducing lung SCC reduced the receptor's activation threshold leading to increased PTHrP expression and secretion. Increasing the expression of either wild-type CaR or a CaR variant with a single nucleotide polymorphism in the cytoplasmic domain was both necessary and sufficient for lung SCC to induce HHM. Because lung cancer patients who frequently develop HHM and PTHrP expression in lung cancer has been only partially explained, the significance of our findings indicates that CaR variants may provide a positive feedback between PTHrP and calcium and result in the syndrome of HHM. PMID:21532883

  4. Inherited variation at chromosome 12p13.33 including RAD52 influences squamous cell lung carcinoma risk

    PubMed Central

    Shi, Jianxin; Chatterjee, Nilanjan; Rotunno, Melissa; Wang, Yufei; Pesatori, Angela C.; Consonni, Dario; Li, Peng; Wheeler, William; Broderick, Peter; Henrion, Marc; Eisen, Timothy; Wang, Zhaoming; Chen, Wei; Dong, Qiong; Albanes, Demetrius; Thun, Michael; Spitz, Margaret R.; Bertazzi, Pier Alberto; Caporaso, Neil E.; Chanock, Stephen J.; Amos, Christopher I.; Houlston, Richard S.; Landi, Maria Teresa

    2011-01-01

    While lung cancer is largely caused by tobacco smoking, inherited genetic factors play a role in its etiology. Genome-wide association studies (GWAS) in Europeans have robustly demonstrated only three polymorphic variations influencing lung cancer risk. Tumor heterogeneity may have hampered the detection of association signal when all lung cancer subtypes were analyzed together. In a GWAS of 5,355 European smoking lung cancer cases and 4,344 smoking controls, we conducted a pathway-based analysis in lung cancer histologic subtypes with 19,082 SNPs mapping to 917 genes in the HuGE-defined “inflammation” pathway. We identified a susceptibility locus for squamous cell lung carcinoma (SQ) at 12p13.33 (RAD52, rs6489769), and replicated the association in three independent samples totaling 3,359 SQ cases and 9,100 controls (odds ratio=1.20, Pcombined=2.3×10−8). Significance The combination of pathway-based approaches and information on disease specific subtypes can improve the identification of cancer susceptibility loci in heterogeneous diseases. PMID:22585858

  5. Enhanced cell killing in lewis lung carcinoma and a human pancreatic-carcinoma xenograft by the combination of cytotoxic drugs and misonidazole.

    PubMed

    Stephens, T C; Courtenay, V D; Mills, J; Peacock, J H; Rose, C M; Spooner, D

    1981-04-01

    The "chemosensitizing" properties of the radiosensitizer misonidazole (MISO) were examined in 2 tumour systems, murine Lewis lung carcinoma and human pancreatic adenocarcinoma xenografted into immune-suppressed mice, using a soft-agar colony assay to measure tumour-cell survival. In mice bearing Lewis lung tumour, the administration of MISO simultaneously with melphalan, cyclophosphamide. CCNU, FU or vincristine gave substantial enhancement of cytotoxicity (DEFs from 1.5 to 3.5). However, no enhancement was seen with bleomycin, VP 16-213 or cis-Pt. The same level of enhancement of cyclophosphamide effect (DEF = 2.0) was seen with both cell survival and growth delay end-points effect (DEF = 2.0) was seen with both cell survival and growth delay end-points of tumour response. Enhancement was also seen in the human tumour xenograft with melphalan, cyclophosphamide and MeCCNU, using a cell survival assay, but cis-Pt was again not enhanced.

  6. 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

  7. 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.

  8. Effects and mechanisms of aloe-emodin on cell death in human lung squamous cell carcinoma.

    PubMed

    Lee, H Z; Hsu, S L; Liu, M C; Wu, C H

    2001-11-23

    Aloe-emodin (1,8-dihydroxy-3-(hydroxymethyl)-anthraquinone) is an active component from the root and rhizome of Rheum palmatum. The study investigated the effects and mechanisms of aloe-emodin-induced cell death in human lung squamous cell carcinoma cell line CH27. Aloe-emodin (40 microM)-induced CH27 cell apoptosis was confirmed by DNA fragmentation (DNA ladders and sub-G(1) formation). Aloe-emodin-induced apoptosis of CH27 cells involved modulation of the expression of Bcl-2 family proteins, such as BclX(L), Bag-1, and Bak, and was associated with the translocation of Bak and Bax from cytosolic to particulate fractions. Aloe-emodin-treated CH27 cells had an increased relative abundance of cytochrome c in the cytosolic fraction. Results demonstrated that the activation of caspase-3, caspase-8, and caspase-9 is an important determinant of apoptotic death induced by aloe-emodin. These results suggest that aloe-emodin induces CH27 cell death by the Bax and Fas death pathway.

  9. 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

  10. 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.

  11. Neuroendocrine differentiation is an independent prognostic factor in chemotherapy-treated nonsmall cell lung carcinoma.

    PubMed

    Schleusener, J T; Tazelaar, H D; Jung, S H; Cha, S S; Cera, P J; Myers, J L; Creagan, E T; Goldberg, R M; Marschke, R F

    1996-04-01

    Neuroendocrine differentiation can be identified in 10-30% of patients with nonsmall cell lung carcinoma (NSCLC) by immunohistochemical or electron microscopic techniques. However, its clinical significance is not well established. Tumors from 107 patients with Stage IIIA, IIIB, and IV NSCLC treated with cisplatin/etoposide with or without hydrazine in the North Central Cancer Treatment Group and Mayo Clinic protocols were analyzed immunohistochemically with antibodies to chromogranin A (CGA), Leu 7 (CD 57), and synaptophysin (SY). These results were compared with clinical outcomes. Keratin AE1/AE3, used as a control, was positive in 99.1% of cases; 34.6% had positive staining for at least 1 neuroendocrine marker, and 11.3% had positive staining for 2 or more markers. CGA was positive in 4.7%, Leu 7 in 18.7%, and SY in 24.3% of cases. A significant increase in survival was seen in patients with tumors expressing any one neuroendocrine marker or any combination of neuroendocrine markers (P < or = 0.01). There was no correlation between the presence of neuroendocrine differentiation and either response to chemotherapy or time to disease progression (P > 0.3), nor was there any correlation between chemotherapy response, time to progression, or survival with staining intensity or percent of cells positive per case. Neuroendocrine differentiation may be of prognostic significance in patients with advanced stage NSCLC treated with chemotherapy.

  12. Heterogeneity of macrophage infiltration and therapeutic response in lung carcinoma revealed by 3D organ imaging

    PubMed Central

    Cuccarese, Michael F.; Dubach, J. Matthew; Pfirschke, Christina; Engblom, Camilla; Garris, Christopher; Miller, Miles A.; Pittet, Mikael J.; Weissleder, Ralph

    2017-01-01

    Involvement of the immune system in tumour progression is at the forefront of cancer research. Analysis of the tumour immune microenvironment has yielded a wealth of information on tumour biology, and alterations in some immune subtypes, such as tumour-associated macrophages (TAM), can be strong prognostic indicators. Here, we use optical tissue clearing and a TAM-targeting injectable fluorescent nanoparticle (NP) to examine three-dimensional TAM composition, tumour-to-tumour heterogeneity, response to colony-stimulating factor 1 receptor (CSF-1R) blockade and nanoparticle-based drug delivery in murine pulmonary carcinoma. The method allows for rapid tumour volume assessment and spatial information on TAM infiltration at the cellular level in entire lungs. This method reveals that TAM density was heterogeneous across tumours in the same animal, overall TAM density is different among separate pulmonary tumour models, nanotherapeutic drug delivery correlated with TAM heterogeneity, and successful response to CSF-1R blockade is characterized by enhanced TAM penetration throughout and within tumours. PMID:28176769

  13. Frequency of brain metastasis in adenocarcinoma and large cell carcinoma of the lung: correlation with survival

    SciTech Connect

    Komaki, R.; Cox, J.D.; Stark, R.

    1983-10-01

    From January 1970 through December 1981, 469 patients with histologically or cytologically proven adenocarcinoma (AC) (349) and large cell carcinoma (LC) (120) of the lung were seen at the Department of Radiation Oncology, Medical College of Wisconsin Affiliated Hospitals. One quarter (126/469) of these patients had brain metastasis: 48 patients presented with brain metastasis and 78 patients subsequently developed brain metastasis. Brain was the dominant site of metastasis in 82 patients who received only cranial + thoracic irradiation; 37 patients (17 simultaneous, 20 metachronous) also required irradiation of other sites of metastasis. All 17 patients with LC, and 47/61 (77%) with AC who developed metachronous brain metastasis did so within one year. The cumulative probability of brain metastasis increased with survival to the levels predicted by autopsy studies. Therapeutic brain irradiation may result in long-term survival in patients with single organ brain metastasis. Since patients with AC and LC so frequently develop brain metastasis and the brain may be the only site of metastasis, prophylactic cranial irradiation may significantly reduce morbidity and mortality from these diseases.

  14. Radiotherapy plus razoxane for advanced limited extent carcinoma of the lung

    SciTech Connect

    Corder, M.P.; Tewfik, H.H.; Clamon, G.H.; Platz, C.E.; Leimert, J.T.; Herbst, K.D.; Byfield, J.E.

    1984-05-01

    Forty-four patients with limited extent American Joint Committee on Cancer Stage II-III non-small cell carcinoma of the lung were randomly assigned to potentially curative radiation therapy plus one of two schedules of razoxane. The weekly schedule was 1 gram per square meter body surface area (BSA) every 8 hours for two doses per week, and the daily schedule was a fixed dose of 250 mg per day. The 50% Kaplan-Meier survival estimate for both groups combined was 9 months. There was no survival difference between the two dose-schedules. Toxicity was formidable with an 82% incidence of esophagitis, and a 20% incidence of grade III-IV esophagitis. Fifty-nine percent of patients developed hematologic toxicity. This was greater with the weekly dose-schedule (P . 0.01). Forty-one percent of patients developed radiographic or symptomatic pneumonitis. One patient developed a fatal myelitis. This program is no more effective than irradiation alone, and has substantial morbidity.

  15. Glutathione as a protective factor in the cadmium response of human lung carcinoma cells

    SciTech Connect

    Kang, Y.J.; Enger, M.D.

    1987-05-01

    Human lung carcinoma derived A549 cells were studied to determine if their high cadmium resistance relative to most cells is due to their concomitantly higher level of glutathione (GSH). Cellular GSH was 75-85% and 70-80% depleted by exposing A549-T27 cells to 0.5 mM diethylmaleate (DEM) for 4 hours and 10 mM buthionine sulfoximine (BSO) for 8 hours, respectively. Such GSH depletion sensitized the cells to cadmium. The threshold of 5 ..mu..M cadmium for cytotoxic response was eliminated and the LD/sub 50/ was decreased from 31 ..mu..M to 15 and 21 ..mu..M, respectively, in DEM and BSO treated cells. There is no difference in GSH content between a cadmium resistant subpopulation (T27) of A549 and one which is more sensitive (T20). These subpopulations have the same cadmium uptake and kinetics of metallothionein synthesis. However, GSH kinetics following exposure to 5 ..mu..M cadmium differs significantly between the two subpopulations. The results suggest that a higher level of GSH may be an important, but not exclusive, determinant of greater cadmium resistance in A549 cells and that the difference in GSH metabolism may be a determinant of clonal variation of cadmium cytotoxic response in the A549 cells.

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

    PubMed

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

    2016-02-01

    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.

  17. Morphoproteomic Characterization of Lung Squamous Cell Carcinoma Fragmentation, a Histological Marker of Increased Tumor Invasiveness.

    PubMed

    Casanova, Ruben; Xia, Daniel; Rulle, Undine; Nanni, Paolo; Grossmann, Jonas; Vrugt, Bart; Wettstein, Reto; Ballester, Rafael; Astolfo, Alberto; Weder, Walter; Moch, Holger; Stampanoni, Marco; Beck, Andrew H; Soltermann, Alex

    2017-05-15

    Accurate stratification of tumors is imperative for adequate cancer management. In addition to staging, morphologic subtyping allows stratification of patients into additional prognostic groups. In this study, we used an image-based computational method on pan-cytokeratin IHC stainings to quantify tumor fragmentation (TF), a measure of tumor invasiveness of lung squamous cell carcinoma (LSCC). In two independent clinical cohorts from tissue microarrays (TMA: n = 208 patients) and whole sections (WS: n = 99 patients), TF was associated with poor prognosis and increased risk of blood vessel infiltration. A third cohort from The Cancer Genome Atlas (TCGA: n = 335 patients) confirmed the poor prognostic value of TF using a similar human-based score on hematoxylin-eosin staining. Integration of RNA-seq data from TCGA and LC-MS/MS proteomics from WS revealed an upregulation of extracellular matrix remodeling and focal adhesion processes in tumors with high TF, supporting their increased invasive potential. This proposed histologic parameter is an independent and unfavorable prognostic marker that could be established as a new grading parameter for LSCC. Cancer Res; 77(10); 2585-93. ©2017 AACR. ©2017 American Association for Cancer Research.

  18. MCM2 is a therapeutic target of lovastatin in human non-small cell lung carcinomas.

    PubMed

    Zhang, Xu; Teng, Yang; Yang, Fang; Wang, Meng; Hong, Xuan; Ye, Lei-Guang; Gao, Yi-Na; Chen, Gong-Yan

    2015-05-01

    Human non-small cell lung carcinoma (NSCLC) is one of the most common cancer worldwide. In previous studies, lovastatin, acting as an inhibitor of 3-hydroxy-3-methylglutaryl Co A (HMG-CoA) reductase, exhibited significant antitumor activity during tumorigenesis. However, whether or not this effect is mediated through changes in minichromosome maintenance (MCM) 2 expression remains unclear. The present study investigated whether lovastatin inhibits proliferation due to MCM2 in NSCLCs. We first assessed the effects of lovastatin on cell anti-proliferation, cell cycle progression and apoptosis in NSCLC cells. We found, by quantitative RT-PCR and western blot analysis, that lovastatin treatment markedly and consistently inhibited the expression of MCM2. Then, to further explore the anticancer mechanism of lovastatin involving MCM2, we silenced MCM2 by siRNA in two cell lines (A549 and GLC-82). Silencing of MCM2 triggered G1/S arrest. Following further examination of cell cycle-related factors, MCM2 knockdown inhibited protein retinoblastoma (Rb), cyclin D1 and CDK4 expression, but increased p21 and p53 expression, suggesting that siMCM2 indeed triggered cell cycle arrest. In addition, siMCM2 induced apoptosis. Finally, lovastatin treatment increased p-JNK, which is involved in the downregulation of MCM2. In conclusion, our data suggest that MCM2 may be a novel therapeutic target of lovastatin treatment in NSCLCs.

  19. Apoptosis induction of human lung carcinoma cells by Chan Su (Venenum Bufonis) through activation of caspases.

    PubMed

    Yun, Hye Ri; Yoo, Hwa Seung; Shin, Dong Yeok; Hong, Su Hyun; Kim, Jong-Hwan; Cho, Chong Kwan; Choi, Yung Hyun

    2009-09-01

    Chan Su is a traditional Chinese medicine prepared from the dried white secretion of the auricular and skin glands of toads, and has been used as an oriental drug for the treatment of a number of diseases, including cancer. In this study, the potential of Chan Su (skin of Venenum Bufonis) to induce apoptosis in human lung carcinoma A549 cells was investigated. Treatment of A549 cells with skin of Venenum Bufonis resulted in the inhibition of cell growth and viability and the induction of apoptosis, which was shown by trypan blue counts, MTT assay, DAPI staining and flow cytometry analysis. The increase in apoptosis that was induced by skin of Venenum Bufonis was correlated with down-regulation of anti-apoptotic Bcl-2 expression, up-regulation of pro-apoptotic Fas ligand and death receptor 4, and a decrease in the mitochondrial membrane potential. Skin of Venenum Bufonis treatment induced the proteolytic activation of caspases and a concomitant degradation of poly(ADP-ribose)-polymerase and beta-catenin protein. Cleavage of Bid and a down-regulation of the inhibitor of apoptosis family proteins were also observed in skin of Venenum Bufonis-treated A549 cells. Data from this study indicates that SVB induces the apoptosis of A549 cells through a signaling cascade of death receptor-mediated extrinsic and mitochondria-mediated intrinsic caspase pathways.

  20. Effect of resection on local failure in irradiated non-oat cell carcinoma of the lung

    SciTech Connect

    Katz, H.R.

    1983-12-01

    From January 1969 through December 1979, 171 patients completed a course of high dose definitive radiotherapy alone for non-oat cell carcinoma of the lung. During the same period, 53 patients completed a course of definitive postoperative radiotherapy after undergoing resection of the primary tumor. The two groups were otherwise very similar with regard to patient related and tumor related variables. A detailed analysis of the incidence of clinically documented local (in-field) failure on the basis of clinical T and N stages was performed. A comparison of the incidence of local failure as the first site of failure for patients with T/sub 1-2/ tumors demonstrated a statistically significant decrease in local failure in patients whose primary tumors were resected. Histology (epidermoid vs. non-epidermoid) had no apparent effect on the frequency of local failure, either with or without resection. A review of past experience indicates that local failure is common after definitive irradiation alone, and is due to a low rate of sterilization of the primary tumor, even with tolerance doses of irradiation. Data are presented to support a reappraisal of the role of combined resection and irradiation in future clinical trials, to reduce the present unacceptably high rate of local failure in potentially curable patients treated by irradiation alone.

  1. 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.

  2. Effect of postoperative radiotherapy on changes in pulmonary function in patients with stage II and IIIA lung carcinoma

    SciTech Connect

    Choi, N.C.; Kanarek, D.J.; Grillo, H.C. )

    1990-01-01

    To assess the pulmonary tolerance to postoperative radiotherapy (RT) in patients with resected lung carcinoma, a prospective study was begun in January 1977, which consisted of (a) initial pulmonary function test (PFT) and arterial blood gases (ABG) at 1 month after surgery, and before beginning of postoperative RT, and (b) follow-up PFT and ABG 1 year after postoperative RT and then every year thereafter. As of December 1987, 137 patients have been enrolled into this study, and 71 patients who were free of recurrence were subjected to the follow-up PFT and ABG. The remaining 66 patients were unable to complete the follow-up studies because of recurrent carcinoma in 60, refusal to participate in the study in 5 patients even in the absence of significant respiratory symptoms, and progressive asbestos-related pleural thickening in 1 patient. The patient characteristics were as follows: Age ranged from 27 to 79 years with the median of 59 years; sex ratio was 1.4 to 1 for male to female; surgical procedures included lobectomy in 49 and pneumonectomy in 22 patients; tumor extent consisted of Stages T1-T2N1M0 in 44, T1-T2N2M0 in 9, and T3N0-N2M0 in 18 patients, respectively. Histologic types included squamous cell carcinoma in 26, adenocarcinoma in 42, small cell carcinoma in 1, and large cell carcinoma in 2 patients. Target volume for RT included the ipsilateral hilum, the mediastinum, and the thoracic inlet including both supraclavicular fossae. A total dose of 54 Gy was delivered in 1.8 Gy of daily fractions, 5 days per week over a period of 6 weeks. Contrary to expectation, there were minor changes in PFT indices in both lobectomy and pneumonectomy patients. The follow-up PFT in the lobectomy group showed small -3% to +2% changes in mean values of ventilatory indices, lung volume, and ABG.

  3. Antioxidant activity and cytotoxicity of Cyrtosperma johnstonii extracts on drug sensitive and resistant leukemia and small cell lung carcinoma cells.

    PubMed

    Okonogi, Siriporn; Khonkarn, Ruttiros; Mankhetkorn, Samlee; Unger, Frank M; Viernstein, Helmut

    2013-03-01

    The number of patients with cancer is increasing. New therapeutic agents to overcome drug-resistant tumors are urgently needed. Cyrtosperma johnstonii N.E. Br. (Araceae) is used for treatment of cancer in Thai traditional medicine. This study aimed to evaluate antioxidant activity and cytotoxicity of C. johnstonii extracts on human cancer cells. Dried powder of C. johnstonii rhizomes was extracted with several solvents. The 0.1 mg/ml extract solution was tested for antioxidant activity by 2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and ferric reducing antioxidant power (FRAP) assays. Color formation from 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide was used to determine cell viability. Standardization of the extract was performed by high-performance liquid chromatography (HPLC) with photodiode array detector at 254 and 360 nm. Cell cycle arrest was evaluated by flow cytometry after 5 min, 12 h and 24 h treated with 20 µg/ml of the acetone extract. The acetone extract exhibited the highest phenolic content and antioxidant activity (TEAC and EC values = 19.2 ± 0.14 and 19.2 ± 0.31 mM/mg, respectively). The IC₅₀ values for leukemia ranged from 11 ± 1 to 29 ± 3 µg/ml and from 5 ± 2 to 6 ± 0 µg/ml for small cell lung carcinoma cells. Cell cycle arrest occurred at the G2/M phase followed by apoptosis. HPLC analysis revealed that rutin is the major constituents of the extract. The acetone extract of C. johnstoni is a promising source of natural antioxidants and anticancer. The extract inhibits cancer cells effectively with less effect on normal cells.

  4. 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.

  5. 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

  6. Preferential action of liposome-entrapped 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea on lung metastasis of Lewis lung carcinoma as compared with the free drug.

    PubMed

    Inaba, M; Yoshida, N; Tsukagoshi, S

    1981-06-01

    Lipid vesicles entrapping a lipophilic antitumor agent, 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (MeCCNU), within the membrane phase were prepared and their antimetastatic activity was compared with that of free MeCCNU using intravenously inoculated Lewis lung carcinoma. It was found that the liposome preparation exhibited more potent inhibitory activity than the free drug on colony formation in the lung, when administered intravenously as well as intraperitoneally. Superior life-prolongation effect was also observed with liposome preparations as compared with the free drug in this system. However, the two forms of MeCCNU showed almost the same activity against not only Lewis lung carcinoma but also P388 leukemia inoculated subcutaneously and intraperitoneally, respectively. These results suggest that the superior effect of liposome-entrapped MeCCNU on lung metastasis might be due, at least in part, to preferential distribution of liposomes to the lung as compared with the free drug.

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

    ClinicalTrials.gov

    2016-12-20

    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

  8. Lung carcinomas decrease the number of monocytes/macrophages (CD14+ cells) that produce TNF-alpha.

    PubMed

    Lopez-Gonzalez, Jose Sullivan; Avila-Moreno, Federico; Prado-Garcia, Heriberto; Aguilar-Cazares, Dolores; Mandoki, Juan Jose; Meneses-Flores, Manuel

    2007-03-01

    The role that inflammation plays in cancer is puzzling. In peripheral blood, TNF-alpha-producing monocytes (CD14+ cells) were compared among patients with lung cancer, patients with tuberculosis and healthy donors; also, in pleural effusion TNF-alpha-producing CD14+ cells were compared between tuberculous patients and lung cancer patients. To analyze the level of the cellular alteration in TNF-alpha production, an experimental model was set up. TNF-alpha-producing CD14+ cells in peripheral blood from lung cancer patients were significantly lower than those from healthy donors. In pleural effusion, TNF-alpha-producing CD14+ cells were significantly lower in lung cancer patients than in tuberculous patients. Based on the results obtained from an experimental model, we suggest that this phenomenon was attributed to a reduced expression of TNF-alpha transcript. These findings provide evidence that lung carcinomas reduce TNF-alpha production by macrophages, possibly by inducing in these cells an M2 phenotype, which favor tumor progression.

  9. AT2R Gene Delivered by Condensed Polylysine Complexes Attenuates Lewis Lung Carcinoma after Intravenous Injection or Intratracheal Spray.

    PubMed

    Alhakamy, Nabil A; Ishiguro, Susumu; Uppalapati, Deepthi; Berkland, Cory J; Tamura, Masaaki

    2016-01-01

    Transfection efficiency and toxicity concerns remain a challenge for gene therapy. Cell-penetrating peptides (CPP) have been broadly investigated to improve the transfection of genetic material (e.g., pDNA and siRNA). Here, a synthetic CPP (polylysine, K9 peptide) was complexed with angiotensin II type 2 receptor (AT2R) plasmid DNA (pAT2R) and complexes were condensed using calcium chloride. The resulting complexes were small (∼150 nm) and showed high levels of gene expression in vitro and in vivo. This simple nonviral formulation approach showed negligible cytotoxicity in four different human cell lines (cervix, breast, kidney, and lung cell lines) and one mouse cell line (a lung cancer cell line). In addition, this K9-pDNA-Ca(2+) complex demonstrated cancer-targeted gene delivery when administered via intravenous injection or intratracheal spray. The transfection efficiency was evaluated in Lewis lung carcinoma (LLC) cell lines cultured in vitro and in orthotopic cancer grafts in syngeneic mice. Immunohistochemical analysis confirmed that the complex effectively delivered pAT2R to the cancer cells, where it was expressed mainly in cancer cells along with bronchial epithelial cells. A single administration of these complexes markedly attenuated lung cancer growth, offering preclinical proof-of-concept for a novel nonviral gene delivery method exhibiting effective lung tumor gene therapy via either intravenous or intratracheal administration.

  10. 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

  11. Differential expression of hypoxia inducible factor-1 alpha and tumor cell proliferation between squamous cell carcinomas and adenocarcinomas among operable non-small cell lung carcinomas.

    PubMed Central

    Lee, Chang Hun; Lee, Min Ki; Kang, Chi Duk; Kim, Young Dae; Park, Do Youn; Kim, Jee Yeon; Sol, Mee Young; Suh, Kang Suek

    2003-01-01

    This study aimed to evaluate whether the elevated level of hypoxia-inducible factor-1alpha (HIF-1alpha) correlated with histologic types, angiogenesis, tumor cell proliferation, and clinical parameters in common non-small cell lung carcinomas (NSCLCs). We performed immunohistochemical stains using paraffin-embedded tissue blocks from 84 cases of operable NSCLC [No. of squamous cell carcinoma (SCC), 45; No. of adenocarcinoma (AC), 39]. HIF-1alpha expression was related with histologic types (66.7% in SCCs vs 20.5% in ACs, p<0.001), but not with lymph node status, tumor stage, vascular endothelial growth factor expression, microvessel density (MVD), and proliferating cell nuclear antigen (PCNA) index (p>0.05, respectively). As for the histologic types, MVD and PCNA index were significantly higher in SCCs than in ACs (p=0.009 and p=0.016, respectively). Among HIF-1alpha positive carcinomas, MVD was significantly higher in HIF-1alpha positive SCCs than in HIF-1alpha positive ACs (p=0.023). The overall survival curves were not associated with HIF-1alpha expression or any other histologic parameters (p>0.05). These findings suggest that HIF-1alpha expression in NSCLCs may play a differential role according to histologic types, but its prognostic significance is indeterminate. PMID:12692416

  12. Monocyte chemotactic protein-1 deficiency attenuates and high-fat diet exacerbates bone loss in mice with Lewis lung carcinoma.

    PubMed

    Yan, Lin; Nielsen, Forrest H; Sundaram, Sneha; Cao, Jay

    2017-04-04

    Bone loss occurs in obesity and cancer-associated complications including wasting. This study determined whether a high-fat diet and a deficiency in monocyte chemotactic protein-1 (MCP-1) altered bone structural defects in male C57BL/6 mice with Lewis lung carcinoma (LLC) metastases in lungs. Compared to non-tumor-bearing mice, LLC reduced bone volume fraction, connectivity density, trabecular number, trabecular thickness and bone mineral density and increased trabecular separation in femurs. Similar changes occurred in vertebrae. The high-fat diet compared to the AIN93G diet exacerbated LLC-induced detrimental structural changes; the exacerbation was greater in femurs than in vertebrae. Mice deficient in MCP-1 compared to wild-type mice exhibited increases in bone volume fraction, connectivity density, trabecular number and decreases in trabecular separation in both femurs and vertebrae, and increases in trabecular thickness and bone mineral density and a decrease in structure model index in vertebrae. Lewis lung carcinoma significantly decreased osteocalcin but increased tartrate-resistant acid phosphatase 5b (TRAP 5b) in plasma. In LLC-bearing mice, the high-fat diet increased and MCP-1 deficiency decreased plasma TRAP 5b; neither the high-fat diet nor MCP-1 deficiency resulted in significant changes in plasma concentration of osteocalcin. In conclusion, pulmonary metastasis of LLC is accompanied by detrimental bone structural changes; MCP-1 deficiency attenuates and high-fat diet exacerbates the metastasis-associated bone wasting.

  13. Combined videothoracoscopic and videomediastinoscopic approach improves radicality of minimally invasive mediastinal lymphadenectomy for early stage lung carcinoma.

    PubMed

    Witte, Biruta; Messerschmidt, Antje; Hillebrand, Hubertus; Gross, Stefan; Wolf, Michael; Kriegel, Elke; Neumeister, Wolfgang; Hürtgen, Martin

    2009-02-01

    To assess the feasibility and radicality of a combined thoracoscopic and mediastinoscopic approach to mediastinal lymphadenectomy compared to thoracoscopy only for minimally invasive management of early stage lung carcinoma. Prospective observational study of patients undergoing anatomical thoracoscopic lung resection for lung carcinoma in our department in 2007. Mediastinal lymphadenectomy was performed either thoracoscopically (VATS group) or by a combination of video-assisted mediastinoscopic lymphadenectomy (VAMLA) and thoracoscopy (VAMLA+VATS group). Inclusion criteria for the study were: stage Ia on CT scan, no central tumor at bronchoscopy, and no contraindications against lobectomy or segmentectomy. Eighteen VAMLA+VATS and fourteen VATS patients were studied. For histology, pTNM stage, type of resection, semiquantitative assessment of the fissure and vascular dissection plane, conversions, blood loss, operation time, adverse events and drainage time, no differences between the two groups were observed. In the VATS group, there was a slight preponderance of women, and right-sided tumors. In the VAMLA+VATS group, both the number of dissected mediastinal lymph node stations (mean, 6.4 stations vs 3.6 stations) and the weight of the mediastinal specimen (median, 11.2 groups vs 5.5 groups), were significantly higher than in the VATS group (p<0.05). A combined approach by VATS and VAMLA improves radicality of minimally invasive mediastinal lymphadenectomy without increase in operation time, morbidity, and drainage time.

  14. Elevated eukaryotic elongation factor 2 expression is involved in proliferation and invasion of lung squamous cell carcinoma

    PubMed Central

    Hao, LiHong; Hu, Jun; Du, Sha; Zhou, Xin; Zhang, LiYuan; Liu, Lu; Gong, LinLin; Chi, XinMing; Liu, Qiang; Shao, ShuJuan

    2016-01-01

    Eukaryotic elongation factor 2 (EF2), is a critical enzyme solely responsible for catalyzing the translocation of the elongated peptidyl-tRNA from the A to P sites of the ribosome during the process of protein synthesis. EF2 is found to be highly expressed in a variety of malignant tumors and is correlated with cancer cell progression and recurrence. The present study was designed to uncover the function of EF2 on lung squamous cell carcinoma (LSCC) cancer cell growth and progression. Our results from clinical tissue studies showed that EF2 protein was significantly overexpressed in LSCC tissues, compared with the adjacent normal lung tissues, which was confirmed by western blotting and tissue microarray. Forced expression of EF2 resulted in the enhancement of lung squamous carcinoma NCI-H520 cells growth through promotion of G2/M progression in cell cycle, activating Akt and Cdc2/Cyclin B1. In nude mice cancer xenograft model, overexpression of EF2 significantly facilitated cell proliferation in vivo. Furthermore, forced expression of EF2 in the cells increased the capabilities of migration and invasion by changing the expressions of EMT-related proteins and genes. These results provided novel insights into the role of EF2 in tumorigenesis and progression in LSCC. EF2-targeted therapy could become a good strategy for the clinical treatment of LSCC. PMID:27542262

  15. Giant hepatic metastasis in a patient with coin-like small cell lung carcinoma incidentally diagnosed at autopsy

    PubMed Central

    Fodor, Decebal; Gurzu, Simona; Contac, Anca Otilia; Jung, Ioan

    2017-01-01

    Abstract Rationale: Encephalopathy is a rare complication of hepatic metastases. In this paper we present a case of a patient with lung cancer and metastatic-related giant hepatomegaly. Patient concerns: A 78-year-old previously healthy male was admitted in the Emergency room in hepatic coma. Diagnoses: The abdominal CT scan examination revealed a huge liver filled with solid nodules. Interventions: No interventions were performed. Outcomes: The patient died at few hours after hospitalization. The autopsy showed a 6.5 kilograms liver with several whitish metastatic nodules and an occult prostate adenocarcinoma. The hilum of both lungs was free of tumor and a 10 mm white nodule was identified surrounding a small bronchus. No peripheral nodules were macroscopically identified. Under microscope, cluster of small cells were observed encasing a small bronchus with multiple minute coin-shaped subpleural foci. A massive intrapulmonary angiolymphatic invasion and metastases from small cell carcinoma in liver, lymph nodes and iliac crest bone marrow were also diagnosed. Lessons: This case highlights the difficulty of diagnosis of aggressive lung carcinomas and the necessity of checking for metachronous tumors. The encephalopathy might be the result of metastatic damage of the liver parenchyma combined with the paraneoplastic effect of the tumor cells. Few than 25 cases of SCLCs with diffuse liver metastases and fulminant liver failure were reported to December 2016. This is the first reported case with a synchronous prostate cancer and a “coin-like” aspect of the SCLC. PMID:28296775

  16. Microwave induces apoptosis in A549 human lung carcinoma cell line.

    PubMed

    Song, Xiao-lian; Wang, Chang-hui; Hu, Hai-yang; Yu, Chao; Bai, Chong

    2011-04-01

    Microwaves have other biological effects on cancer as well besides killing tumor cells by coagulation. Some studies showed that microwaves may induce apoptosis in some tumor cells. The apoptotic effect of microwaves may help in clinic to remove residual malignant cells nearby the primary lesion and avoid relapse subsequently. However, there is little evidence on this subject from lung cancer. We studied the effect of microwaves on inducing apoptosis in the human lung carcinoma cell line A549 cells, aiming to identify its effect on apoptosis. A549 cells were radiated by various intensities and durations of microwaves. Apoptosis induction in A549 cells was analyzed by morphological observations, tetrazolium blue color method (MTT) assays, flow cytometry, immunohistochemistry, and image analyses. Morphological changes in A549 cells, including cell shrinking and nuclear pyknosis, were observed after microwave radiation. Microwaves significantly inhibited metabolic activities and induced apoptosis in A549 cells. The results of the MTT assay showed a significant decrease of cell activities in all the radiation groups compared with the normal control (P < 0.01). The low point of cell activities often appeared at 6 - 12 hours after radiation. Apoptosis was also confirmed by flow cytometry. The early stage apoptotic rate reached 6.10% - 17.98% and the advanced stage apoptotic rate + necrosis rate reached 8.04% - 44.06% at 6 hours after microwave irradiation, in contrast to 2.32% and 4.10% in the respective control groups. Down-regulation of Bcl-2 expression and up-regulation of p53 expression were observed by immunohistochemistry after radiation. In most treated groups, the down-regulation of Bcl-2 expression reached its lowest level at 3 - 6 hours after radiation (integrated optical density (IOD)-6 hours: 2.13 ± 0.08 - 5.14 ± 0.13 vs. control: 5.79 ± 0.10, P < 0.01) and the up-regulation of P53 expression peaked at about 3 hours (IOD-3 hours: 2.61 ± 0.13 - 8.07 ± 0

  17. Expression of syndecan-1 and expression of epidermal growth factor receptor are associated with survival in patients with nonsmall cell lung carcinoma.

    PubMed

    Shah, Lori; Walter, Kristin L; Borczuk, Alain C; Kawut, Steven M; Sonett, Joshua R; Gorenstein, Lyall A; Ginsburg, Mark E; Steinglass, Kenneth M; Powell, Charles A

    2004-10-01

    Recently, the authors identified molecular signatures and pathways associated with nonsmall cell lung carcinoma histology and lung development. They hypothesized that genetic classifiers of histology would provide insight into lung tumorigenesis and would be associated with clinical outcome when evaluated in a broader set of specimens. Associations between patient survival and immunostaining for 11 representative histologic classifiers (epidermal growth factor receptor [EGFR], CDK4, syndecan-1, singed-like, TTF-1, keratin 5, HDAC2, docking protein 1, integrin alpha3, P63, and cyclin D1) were examined using a tissue microarray constructed from nonsmall cell lung carcinoma specimens. Sixty-three tumors were examined, including 43 adenocarcinomas, 11 large cell carcinomas, and 9 squamous cell carcinomas. Sixty-three percent of tumors were clinical Stage I lesions, and 37% were Stage II-III lesions. In a multivariate analysis that controlled for age, gender, and race, syndecan-1 expression was found to be associated with a significant reduction in the risk of death (hazard ratio, 0.31 [95% confidence interval, 0.18-0.87]; P < 0.05). Multivariate analysis also indicated that EGFR expression was associated with a significant reduced risk of death. The authors demonstrated that expression of either of the nonsmall cell lung carcinoma subtype classifiers syndecan-1 and EGFR was associated with a 30% reduction in the risk of death, with this reduction being independent of histology and other confounders. The results of the current study suggest that loss of expression of these histologic classifiers is associated with biologic aggressiveness in lung tumors and with poor outcome for patients with such tumors. If their significance can be validated prospectively, these biomarkers may be used to guide therapeutic planning for patients with nonsmall cell lung carcinoma. (c) 2004 American Cancer Society.

  18. Potential anti-cancer effect of curcumin in human lung squamous cell carcinoma

    PubMed Central

    Zhao, Wei; Wang, Yan; Wang, Ying; Gao, Nan; Han, Zhifeng; Yu, Haixiang

    2015-01-01

    Background To explore the molecular mechanisms of the anti-cancer effect of curcumin in human lung squamous cell carcinoma (LSQCC) SK-MES-1 cells. Methods Cell viability was determined using MTT assay. Ribonucleic acid sequencing was performed to measure expression levels of transcripts in LSQCC cells treated with 15 μmol/L curcumin (treatment groups) or an equal amount of dimethylsulfoxide (control). Cuffdiff software was used to identify differentially expressed genes (DEGs) in treatment groups, followed by enrichment analysis of DEGs using the Database for Annotation, Visualization and Integration Discovery. The protein-protein interaction (PPI) networks for up and downregulated DEGs were constructed by Cytoscape software using Search Tool for the Retrieval of Interacting Genes data to identify hub nodes. Results Curcumin significantly reduced cell viability in LSQCC cells. In total, 380 DEGs including 154 upregulated and 126 downregulated genes were found in the treatment groups. The upregulated genes were enriched in base excision repair (BER, such as PCNA, POLL, and MUTYH) and Janus kinase-signal transducer and activator of transcription (JAT-STAT) signaling pathways (such as AKT1 and STAT5A), while the downregulated genes were enriched in nine pathways, including the vascular endothelial growth factor (VEGF) signaling pathway (such as PTK2, VEGFA, MAPK1, and MAPK14) and mitogen-activated protein kinase (MAPK) signaling pathway (ARRB2, MAPK1, MAPK14, and NFKB1). PCNA and AKT1 were the hub nodes in the PPI network of upregulated genes while MAPK1, MAPK14, VEGFA, and NFKB1 were the hub nodes in the PPI network of downregulated genes. Conclusions Curcumin might exert anti-cancer effects on LSQCC via regulating BER, JAT-STAT, VEGF, and MAPK signaling pathways. PMID:26273408

  19. 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. Copyright © 2016 the American Physiological Society.

  20. Pulmonary atelectasis and survival in advanced non-small cell lung carcinoma

    PubMed Central

    2010-01-01

    Atelectasis was reported as a favorable prognostic sign of pulmonary carcinoma; however, the underlying mechanism in those patients is not known. In this study, we aimed to investigate prospectively the potential impact of atelectasis and/or obstructive pneumonitis (AO) on survival and the relation between atelectasis and some laboratory blood parameters. The study was conducted on 87 advanced stage non-small cell lung cancer (NSCLC) patients. Clinical and laboratory parameters of patients at first presentation were recorded, and patients were divided into two groups according to the presence of AO in thorax computed tomography (CT). Survival was calculated using Kaplan-Meier and univariate Cox's regression analyses. Laboratory parameters that might be related with prolonged survival in atelectasis were compared using chi-square, Student's t, and Mann-Whitney U tests. Of the patients, 54% had stage IV disease, and AO was detected in 48.3% of all cases. Overall median survival was 13.2 months for all cases, 10.9 months for patients without AO, and 13.9 months for patients with AO (P = 0.067). Survival was significantly longer in stage III patients with AO (14.5 months versus 9.2 months, P = 0.032), but not in stage IV patients. Patients with AO in stage III had significantly lower platelet counts (P = 0.032) and blood sedimentation rates than did those with no AO (P = 0.045). We concluded that atelectasis and/or obstructive pneumonitis was associated with prolonged survival in locally advanced NSCLC. There was also a clear association between atelectasis and/or obstructive pneumonitis and platelets and blood sedimentation rate. PMID:20636252

  1. Pulmonary atelectasis and survival in advanced non-small cell lung carcinoma.

    PubMed

    Bulbul, Yilmaz; Eris, Bulent; Orem, Asim; Gulsoy, Ayhan; Oztuna, Funda; Ozlu, Tevfik; Ozsu, Savas

    2010-08-01

    Atelectasis was reported as a favorable prognostic sign of pulmonary carcinoma; however, the underlying mechanism in those patients is not known. In this study, we aimed to investigate prospectively the potential impact of atelectasis and/or obstructive pneumonitis (AO) on survival and the relation between atelectasis and some laboratory blood parameters. The study was conducted on 87 advanced stage non-small cell lung cancer (NSCLC) patients. Clinical and laboratory parameters of patients at first presentation were recorded, and patients were divided into two groups according to the presence of AO in thorax computed tomography (CT). Survival was calculated using Kaplan-Meier and univariate Cox's regression analyses. Laboratory parameters that might be related with prolonged survival in atelectasis were compared using chi-square, Student's t, and Mann-Whitney U tests. Of the patients, 54% had stage IV disease, and AO was detected in 48.3% of all cases. Overall median survival was 13.2 months for all cases, 10.9 months for patients without AO, and 13.9 months for patients with AO (P=0.067). Survival was significantly longer in stage III patients with AO (14.5 months versus 9.2 months, P=0.032), but not in stage IV patients. Patients with AO in stage III had significantly lower platelet counts (P=0.032) and blood sedimentation rates than did those with no AO (P=0.045). We concluded that atelectasis and/or obstructive pneumonitis was associated with prolonged survival in locally advanced NSCLC. There was also a clear association between atelectasis and/or obstructive pneumonitis and platelets and blood sedimentation rate.

  2. Staurosporine analogs promote distinct patterns of process outgrowth and polyploidy in small cell lung carcinoma cells.

    PubMed

    Gallala, Hichem; Winter, Jochen; Veit, Nadine; Nowak, Michael; Perner, Sven; Courts, Cornelius; Kraus, Dominik; Janzen, Viktor; Probstmeier, Rainer

    2015-04-01

    We have recently shown that staurosporine mediates the conversion of small cell lung carcinoma (SCLC) cells into a neuron-like process-bearing phenotype. Here, we have extended these studies to the staurosporine analogs K252a, lestaurtinib, PKC412, stauprimide, and UCN-01 and analyzed their influence on process extension, cell cycle distribution, and induction of polyploidy in four SCLC cell lines. In GLC-2 cells, all compounds provoked extensive process formation with the exception of PKC412 that showed no response. In H1184 cells, process formation was predominantly induced by staurosporine and, to lesser extent, in lestaurtinib-, stauprimide-, and UCN-01-treated cells. In the presence of K252a or PKC412, cells became bipolar and spindle shaped or showed pronounced cell flattening. In GLC-36 and SCLC-24H cells, only cell flattening was detectable. Process formation was reversible upon drug removal as shown for GLC-2 and H1184 cells. Fluorescence-activated cell sorting (FACS) and fluorescence in situ hybridization (FISH) analysis indicated the induction of polyploidy in all staurosporine and in two out of four stauprimide-treated SCLC cell lines. For other staurosporine analogs, polyploidy was observed only in UCN-01-treated GLC-36 cells and in K252a-treated H1184 and GLC-36 cells. The presence of staurosporine or its analogs did not alter the constitutive activation pattern of the canonical Akt/PI3K or MEK/extracellular signal-regulated kinase (ERK)1/2 signaling pathways nor could we detect an influence of stauprimide application on the expression level of the c-Myc oncogene. These data demonstrate that in SCLC cells, albeit a higher substrate specificity, staurosporine analogs can induce staurosporine-comparable effects.

  3. Combinational Treatment with Retinoic Acid Derivatives in Non-small Cell Lung Carcinoma In Vitro

    PubMed Central

    Choi, Eun Jung; Whang, Young Mi; Kim, Seok Jin; Kim, Hyun Jin

    2007-01-01

    The growth inhibitory effects of four retinoic acid (RA) derivatives, 9-cis RA, 13-cis RA, N-(4-hydroxyphenyl) retinamide (4-HPR), and all-trans retinoic acid (ATRA) were compared. In addition, the effects of various combinations of these four agents were examined on non-small cell lung carcinoma (NSCLC) cell-lines, and on the expressions of retinoic acid receptors (RARs) and retinoid X receptors (RXRs) on these cells. At the clinically achievable concentration of 1 µM, only 4-HPR inhibited the growths of H1299 and H460 cells-lines. However, retinoic acid receptor β (RARβ) expression was up-regulated on H460 and H1299 cells treated with 1 µM of ATRA, 13-cis RA, or 9-cis RA. All NSCLC cell lines showed growth inhibition when exposed sequentially to 1 µM ATRA and 0.1 µM 4-HPR. In particular, sequential treatment with 1 µM ATRA or 13-cis RA and 4-HPR markedly inhibited H1703 cell growth; these cells exhibited no basal RARβ expression and were refractory to 4-HPR. However, in NSCLC cell lines that expressed RARβ, the expressional levels of RARβ were up-regulated by ATRA alone and by sequential treatment with ATRA and 4-HPR. 4-HPR was found to be the most active of the four agents in terms of NSCLC growth-inhibition. Moreover, sequential treatments with ATRA or 13-cis RA followed by 4-HPR were found to have synergistic growth-inhibitory effects and to regulate RAR expression. PMID:17923756

  4. Activation of large form galanin-LI by extracellular processing in small cell lung carcinoma tissue.

    PubMed

    Yamamoto, Hiroyuki; Iguchi, Kazuaki; Ohno, Satoshi; Yokogawa, Takashi; Nishikawa, Kazuya; Hoshino, Minoru

    2011-10-01

    Galanin is a neuropeptide that is widely distributed in the central and peripheral nervous systems. Some small cell lung carcinoma (SCLC) cell lines such as SBC-3A release only the high-molecular-mass form, with lower molecular mass forms being undetectable. To investigate the mechanism of processing of progalanin to active peptide, we studied galanin-LI in both the culture media of SBC-3A cells and in extracts from in vivo mouse SBC-3A tumors. SBC-3A cells were found to release high molecular mass galanin, but did not release active peptides. In contrast, tumor extract contained both high-molecular-mass galanin, and a cleaved lower-molecular-mass form of the peptide (8, 5 and 2 kDa). The lower-molecular-mass peptide was identified as galanin(1-20) by MALDI-TOF mass spectrometry. We then looked at MMP-2 and MMP-9 release from SBC-3A cells and tumor tissue treated with galanin and progalanin, as revealed by gelatin zymography. Galanin elicited pro-MMP-2 and pro-MMP-9 release from SBC-3A cells and tumor tissue; however, recombinant progalanin induced pro-MMP-2 and pro-MMP-9 release from tumor tissue only. This study has shown that the galanin-LI released from SCLC SBC-3A cells consisted of the high-molecular-mass peptide form, and was processed extracellularly to galanin(1-20). Furthermore, galanin was seen to induce pro-MMP-2 and pro-MMP-9 release from SBC-3A cells.

  5. Cytomorphology of non-small cell lung carcinoma with anaplastic lymphoma kinase gene rearrangement.

    PubMed

    Toll, Adam D; Maleki, Zahra

    2015-01-01

    Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase demonstrating activating mutations in several malignancies including a subset (1-5%) of non-small cell lung carcinomas (NSCLC). Prior work examining, the histologic features of these tumors found a spectrum of findings, notably a solid/acinar pattern, as well as a mucinous cribriform pattern. We present the first study to date describing the cytomorphology of NSCLC harboring ALK rearrangements. A retrospective database search was conducted to identify cytologic specimens of NSCLC demonstrating ALK rearrangement. Cytogenetic analysis was performed with fluorescence in situ hybridization. A total of 12 patients were identified, 10 with available material. Cellular morphology and smear background was evaluated in the study group, as well as control cases lacking ALK rearrangement. A total of 25 specimens from 10 patients were obtained. Five patients never smoked, and four patients had a remote smoking history. ALK rearrangements were identified in cells with unique cytologic characteristics. All cases demonstrated moderate to poor differentiation with a predominance of single cells showing anisonucleosis and frequent intracytoplasmic neutrophils. The control cases showed cells with smaller, less pleomorphic nuclei, and smaller nucleoli with more clusters/tissue fragments. Several unique cytomorphologic features were consistently identified in the study population relative to the control population and include a prominence of single, markedly enlarged tumor cells with plasmacytoid features and anisonucleosis, as well as intracytoplasmic neutrophils. Larger studies are warranted to confirm our preliminary findings, as these features may help establish a more cost-effective means to select patients being tested for ALK mutational analysis. © 2014 Wiley Periodicals, Inc.

  6. Hsp72 mediates TAp73α anti-apoptotic effects in small cell lung carcinoma cells.

    PubMed

    Nyman, Ulrika; Muppani, Naveen Reddy; Zhivotovsky, Boris; Joseph, Bertrand

    2011-08-01

    The transcription factor p73, a member of the p53 family of proteins, is involved in the regulation of cell cycle progression and apoptosis. Due to alternative promoters and carboxy-terminal splicing, the P73 gene gives rise to a range of different isoforms. Interestingly, a particular increase in expression of the TAp73α isoform has been reported in various tumours. In addition, TAp73α has been shown to inhibit Bax activation and mitochondrial dysfunctions and thereby to confer small cell lung carcinoma (SCLC) cells resistance to drug-induced apoptosis. However, the precise mechanism by which TAp73α exerts its pro-survival effect is yet unclear. Here we report that TAp73α, but not TAp73β, regulates the expression of inducible Hsp72/HSPA1A. Hsp72 proved to be required for the survival effects of TAp73α as antisense knockdown of Hsp72 resulted in an abolishment of the anti-apoptotic effect of TAp73α in SCLC cells upon Etoposide treatment. Importantly, depletion of Hsp72 allowed activation of Bax, loss of mitochondrial membrane potential and lysosomal membrane permeabilization in SCLC cells even in the presence of TAp73α. Finally, we revealed that TAp73β counteracts the anti-apoptotic effect of TAp73α by preventing Hsp72 induction. Our results thus provide additional evidence for the potential oncogenic role of TAp73α, and extend the understanding of the mechanism for its anti-apoptotic effect.

  7. Genetic alteration profiling of patients with resected squamous cell lung carcinomas.

    PubMed

    Tao, Dan; Han, Xiaohong; Zhang, Ningning; Lin, Dongmei; Wu, Di; Zhu, Xinxin; Song, Wenya; Shi, Yuankai

    2016-06-14

    In this study, we analyzed the genetic profiles of squamous cell lung carcinoma (SqCLC) to identify potential therapeutic targets. Approximately 2,800 COSMIC mutations from 50 genes were determined by next-generation sequencing. Amplification/deletion of SOX2, CDKN2A, PTEN, FGFR1, EGFR, CCND1, HER2 and PDGFRA were detected by FISH and expression of VEGFR2, PD-L1 and PTEN were examined by IHC. One hundred and fifty-seven samples of SqCLC were collected. Somatic mutations was identified in 73.9% of cases, with TP53 (56.1%), CDKN2A (8.9%), PIK3CA (8.9%), KRAS (4.5%) and EGFR (3.2%). Gene copy number alterations were identified in 75.8% of cases, including SOX2 amplification (31.2%), CDKN2A deletion (21.7%), PTEN deletion (16.6%), FGFR1 amplification (15.9%), EGFR amplification (14.0%), CCND1 amplification (14.0%), HER2 amplification (9.6%) and PDGFRA amplification (7.6%). Positive expression of VEGFR2 and PD-L1 and loss of PTEN expression were observed in 80.5%, 47.2%, and 42.7% of cases, respectively. Multivariate analysis showed that positive expression of PD-L1 was an independent favorable prognostic factor for DFS (HR = 0.610; P = 0.044). In conclusion, nearly all (93.6%) SqCLC cases harbored at least one potential druggable target. The findings of this study could facilitate the identification of therapeutic target candidates for precision medicine of SqCLC.

  8. 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.

  9. 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

  10. Genetic alteration profiling of patients with resected squamous cell lung carcinomas

    PubMed Central

    Zhang, Ningning; Lin, Dongmei; Wu, Di; Zhu, Xinxin; Song, Wenya; Shi, Yuankai

    2016-01-01

    In this study, we analyzed the genetic profiles of squamous cell lung carcinoma (SqCLC) to identify potential therapeutic targets. Approximately 2,800 COSMIC mutations from 50 genes were determined by next-generation sequencing. Amplification/deletion of SOX2, CDKN2A, PTEN, FGFR1, EGFR, CCND1, HER2 and PDGFRA were detected by FISH and expression of VEGFR2, PD-L1 and PTEN were examined by IHC. One hundred and fifty-seven samples of SqCLC were collected. Somatic mutations was identified in 73.9% of cases, with TP53 (56.1%), CDKN2A (8.9%), PIK3CA (8.9%), KRAS (4.5%) and EGFR (3.2%). Gene copy number alterations were identified in 75.8% of cases, including SOX2 amplification (31.2%), CDKN2A deletion (21.7%), PTEN deletion (16.6%), FGFR1 amplification (15.9%), EGFR amplification (14.0%), CCND1 amplification (14.0%), HER2 amplification (9.6%) and PDGFRA amplification (7.6%). Positive expression of VEGFR2 and PD-L1 and loss of PTEN expression were observed in 80.5%, 47.2%, and 42.7% of cases, respectively. Multivariate analysis showed that positive expression of PD-L1 was an independent favorable prognostic factor for DFS (HR = 0.610; P = 0.044). In conclusion, nearly all (93.6%) SqCLC cases harbored at least one potential druggable target. The findings of this study could facilitate the identification of therapeutic target candidates for precision medicine of SqCLC. PMID:27145277

  11. DLC-1 operates as a tumor suppressor gene in human non-small cell lung carcinomas.

    PubMed

    Yuan, Bao-Zhu; Jefferson, Amy M; Baldwin, Kimberly T; Thorgeirsson, Snorri S; Popescu, Nicholas C; Reynolds, Steven H

    2004-02-19

    The deleted in liver cancer (DLC-1) gene at chromosome 8p21-22 is altered mainly by genomic deletion or aberrant promoter methylation in a large number of human cancers such as breast, liver, colon and prostate and is known to have an inhibitory effect on breast and liver tumor cell growth. Given the high frequency of deletion involving region 8p21-22 in human non-small cell lung carcinoma (NSCLC), we examined alterations of DLC-1 in a series of primary tumors and tumor cell lines and tested effects of DLC-1 on tumor cell growth. A significant decrease or absence of the DLC-1 mRNA expression was found in 95% of primary NSCLC (20/21) and 58% of NSCLC cell lines (11/19). Transcriptional silencing of DLC-1 was primarily associated with aberrant DNA methylation, rather than genomic deletion as 5-aza-2'-deoxycytidine induced reactivation of DLC-1 expression in 82% (9/11) NSCLC cell lines showing downregulated DLC-1. It was further evidenced by an aberrant DLC-1 promoter methylation pattern, which was detected by Southern blotting in 73% (8/11) of NSCLC cell lines with downregulation of the gene. The transfer of DLC-1 into three DLC-1 negative cell lines caused a significant inhibition in cell proliferation and/or a decrease in colony formation. Furthermore, stable transfer of DLC-1 abolished tumorigenicity in nude mice of two cell lines, suggesting that DLC-1 plays a role in NSCLC by acting as a bona fide new tumor suppressor gene.

  12. Simultaneous EGFR and VEGF Alterations in Non-Small Cell Lung Carcinoma Based on Tissue Microarrays

    PubMed Central

    Tsiambas, Evangelos; Stamatelopoulos, Athanasios; Karameris, Andreas; Panagiotou, Ioannis; Rigopoulos, Dimitrios; Chatzimichalis, Antonios; Bouros, Demosthenes; Patsouris, Efstratios

    2007-01-01

    Background: Epidermal growth factor receptor (EGFR) overexpression is observed in significant proportions of non-small cell lung carcinomas (NSCLC). Furthermore, overactivation of vascular endothelial growth factor (VEGF) leads to increased angiogenesis implicated as an important factor in vascularization of those tumors. Patients and Methods: Using tissue microarray technology, forty-paraffin (n = 40) embedded, histologically confirmed primary NSCLCs were cored and re-embedded into a recipient block. Immunohistochemistry was performed for the determination of EGFR and VEGF protein levels which were evaluated by the performance of computerized image analysis. EGFR gene amplification was studied by chromogenic in situ hybridization based on the use of EGFR gene and chromosome 7 centromeric probes. Results: EGFR overexpression was observed in 23/40 (57.5%) cases and was correlated to the stage of the tumors (p = 0.001), whereas VEGF was overexpressed in 35/40 (87.5%) cases and was correlated to the stage of the tumors (p = 0.005) and to the smoking history of the patients (p = 0.016). Statistical significance was assessed comparing the protein levels of EGFR and VEGF (p = 0.043, k = 0.846). EGFR gene amplification was identified in 2/40 (5%) cases demonstrating no association to its overall protein levels (p = 0.241), whereas chromosome 7 aneuploidy was detected in 7/40 (17.5%) cases correlating to smoking history of the patients (p = 0.013). Conclusions: A significant subset of NSCLC is characterized by EGFR and VEGF simultaneous overexpression and maybe this is the eligible target group for the application of combined anti-EGFR/VEGF targeted therapies at the basis of genetic deregulation (especially gene amplification for EGFR). PMID:19455247

  13. Inhibition of 12-lipoxygenase during baicalein-induced human lung nonsmall carcinoma H460 cell apoptosis.

    PubMed

    Leung, Henry W C; Yang, W H; Lai, M Y; Lin, C J; Lee, H Z

    2007-03-01

    Baicalein is known as a 12-lipoxygenase (12-LOX) inhibitor. The 12-LOX is found to be involved in the progression of human cancers and the inhibitor of 12-LOX offers a target for the prevention cancer. We demonstrated the inhibitory effect of baicalein on the gene and protein expression of 12-LOX in H460 human lung nonsmall carcinoma cell line. Treatment of baicalein inhibited the growth of H460 cells in a dose-dependent manner. Following 24h exposure to 50muM baicalein, cell cycle analysis revealed an increase in the cell population in S-phase. During the S-phase arrest, baicalein decreased the protein levels of cdk1 and cyclin B1, which are the regulating proteins of S-phase transition to G2/M-phase, in this study. Furthermore, baicalein induced the most of H460 cell apoptosis after treatment for 48h. H460 cells formed vesicles and apoptotic body, and then floated after treatment with baicalein. Baicalein-induced H460 cell apoptosis was confirmed by DNA condensation and fragmentation. Baicalein-induced apoptosis were also accompanied by decreasing in Bcl-2 and proform of caspase-3 and increasing p53 and Bax protein levels. Pretreatment with a specific caspase-3 inhibitor, Ac-DEVD-CHO, partially reduced baicalein-induced cell death, indicating baicalein induces apoptosis is partially dependent on caspase-3 pathway in H460 cells. These data suggest that baicalein, a 12-LOX inhibitor, inhibits the proliferation of H460 cells via S-phase arrest and induces apoptosis in association with the regulation of molecules in the cell cycle and apoptosis-related proteins.

  14. ATP sensitizes H460 lung carcinoma cells to cisplatin-induced apoptosis.

    PubMed

    Swennen, Els L R; Ummels, Vanessa; Buss, Irina; Jaehde, Ulrich; Bast, Aalt; Dagnelie, Pieter C

    2010-03-30

    Platinum resistance of cancer cells may evolve due to a decrease in intracellular drug accumulation, decreased cell permeability or by an increased deactivation of the drug by glutathione (GSH). The aim of this study was (1) to investigate the effect of adenosine 5'-triphosphate (ATP) on the cytotoxicity of cisplatin in a large cell lung carcinoma cell line (H460), and (2) to examine the potential involvement of increased cisplatin uptake, GSH depletion and pyrimidine starvation by ATP in this effect. H460 cells were harvested and seeded (5% CO(2); 37 degrees C). Subsequently, cells were incubated with medium or ATP followed by an incubation with cisplatin. Cytotoxicity screening was analyzed by the sulforhodamine B (SRB) colorimetric assay, lactate dehydrogenase and caspase-3/7 activity. Pre-incubation for 72h with 0.3 and 3mM ATP strongly enhanced the anti-proliferative potency of cisplatin 2.9- and 7.6-fold, respectively. Moreover, after incubation of H460 cells with 0.3mM ATP the intracellular platinum concentration increased, indicating increased cisplatin uptake by ATP. ATP, despite lowering the LD(50) of cisplatin, did not modulate GSH levels in H460 cells. ATP itself showed a biphasic effect on H460 cell growth: 0.3mM inhibited H460 cell growth via the pyrimidine starvation effect, activation of caspase-3/7 and LDH leakage, while 3mM ATP showed no effect on cell growth. In conclusion, ATP sensitizes the H460 cells to cisplatin-induced apoptosis. The effect of 0.3mM ATP is not due to GSH depletion but involves increased cisplatin uptake and pyrimidine starvation due to ATP conversion to adenosine followed by cellular uptake.

  15. Administration of vitamin D3 improves antimetastatic efficacy of cancer vaccine therapy of Lewis lung carcinoma.

    PubMed

    Zhuravel, E; Efanova, O; Shestakova, T; Glushko, N; Mezhuev, O; Soldatkina, M; Pogrebnoy, P

    2010-03-01

    To analyze antitumor efficacy of experimental cancer vaccine therapy combined with introduction of vitamin D3 (VD3) for treatment of Lewis lung carcinoma (3LL). Cancer vaccines composed from recombinant murine beta-defensin-2 (mBD-2) and 3LL cell lysate, or DNA, coding for mBD-2-Muc1 fusion construct cloned in pcDNA3+ vector, were prepared and used for intradermal vaccination. Experimental cancer vaccines introduced i. d. at therapeutic and prophylactic regimens to 3LL-bearing C57Bl mice, were applied alone or in combination with VD3 (administered per os) and/or low-dose cyclophosphamide (CP, administered intraperitoneal). Efficacy of treatments was analyzed by primary tumor growth dynamics indexes and by metastasis rate in vaccinated animals. As it has been shown, administration of the protein-based vaccine composed from mBD-2 and 3LL cell lysate in combination with VD3 and CP, but not in VD3 free setting, led to significant suppression of primary tumor growth (p < 0.005) and had significant antimetastatic effect. Introduction of VD3 with or without CP in the scheme of treatment with mBD- 2-Muc1-DNA vaccine at therapeutic regimen has led to significant suppression of primary tumor (p < 0.05) and metastasis volumes (p < 0.005), while in the groups of animals treated with DNA-vaccine + VD3 with or without CP at prophylactic regimen, significant antimetastatic effect (p < 0.05) and elevation of average life-span (p < 0.05) have been registered. The results of this pilot study have shown promising clinical effects of VD3 administration in combination with cancer vaccinotherapy in vivo.

  16. 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

  17. Lung Carcinoma Predictive Biomarker Testing by Immunoperoxidase Stains in Cytology and Small Biopsy Specimens: Advantages and Limitations.

    PubMed

    Zhou, Fang; Moreira, Andre L

    2016-12-01

    - In the burgeoning era of molecular genomics, immunoperoxidase (IPOX) testing grows increasingly relevant as an efficient and effective molecular screening tool. Patients with lung carcinoma may especially benefit from the use of IPOX because most lung carcinomas are inoperable at diagnosis and only diagnosed by small tissue biopsy or fine-needle sampling. When such small specimens are at times inadequate for molecular testing, positive IPOX results still provide actionable information. - To describe the benefits and pitfalls of IPOX in the detection of biomarkers in lung carcinoma cytology specimens and small biopsies by summarizing the currently available commercial antibodies, preanalytic variables, and analytic considerations. - PubMed. - Commercial antibodies exist for IPOX detection of aberrant protein expression due to EGFR L858R mutation, EGFR E746_A750 deletion, ALK rearrangement, ROS1 rearrangement, and BRAF V600E mutation, as well as PD-L1 expression in tumor cells. Automated IPOX protocols for ALK and PD-L1 detection were recently approved by the Food and Drug Administration as companion diagnostics for targeted therapies, but consistent interpretive criteria remain to be elucidated, and such protocols do not yet exist for other biomarkers. The inclusion of cytology specimens in clinical trials would expand patients' access to testing and treatment, yet there is a scarcity of clinical trial data regarding the application of IPOX to cytology, which can be attributed to trial designers' lack of familiarity with the advantages and limitations of cytology. The content of this review may be used to inform clinical trial design and advance IPOX validation studies.

  18. Expression of the CXCR4 ligand SDF-1/CXCL12 is prognostically important for adenocarcinoma and large cell carcinoma of the lung.

    PubMed

    Sterlacci, William; Saker, Shereen; Huber, Bettina; Fiegl, Michael; Tzankov, Alexandar

    2016-04-01

    The SDF-1/CXCR4 axis is associated with tumor progression and has been reported as a prognostic parameter, although with conflicting data for non-small cell lung cancer (NSCLC). This study examines a large cohort of clinically and pathologically well-characterized NSCLC patients and includes the activated form of CXCR4 (pCXCR4), which has not been studied in this context so far. SDF-1, CXCR4, and pCXCR4 were assessed immunohistochemically in 371 surgically resected NSCLC using a standardized tissue microarray platform. Extensive clinical and pathological data and a postoperative follow-up period of 17 years enabled detailed correlations. CXCR4 and pCXCR4 were frequently expressed on squamous cell carcinoma. Membranous expression of SDF-1 was a marker of poor prognosis and proved to be an independent prognostic parameter for the entire cohort and for patients with adenocarcinoma (ACA) and large cell carcinoma (LCC). Targeted cancer therapies blocking SDF-1/CXCR4 interaction already exist, and our data suggest that expression of SDF-1, especially on poorer prognosis subgroups of LCC and ACA, indicates patients that might benefit more than others. This should be taken into account when assessing the effectiveness of such targeted approaches for NSCLC patients and could lead to important implications.

  19. 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.

  20. Small bowel intussusception caused by multiple intestinal metastases from a giant cell carcinoma of the lung: a case report.

    PubMed

    Mandeville, Y; de Gheldere, C; Vanclooster, P

    2015-01-01

    Small bowel obstruction (SBO) due to intussusception in adults is a rare condition. Diagnosis at the time of admission is usually challenging. More often than not, a bowel intussusception in adults is secondary to an organic condition, frequently malignancies. Therefore, a surgical approach is indicated most of the times. We report the case of a forty-nine years old lady presenting with a SBO secondary to small bowel metastases with two ileo-ileal intussusceptions, one of which was missed at initial surgical exploration. A giant cell carcinoma of the lung (GCCL) with small bowel metastases was diagnosed subsequently. The case is presented as well as a brief review of literature.

  1. Small Bowel Intussusception Caused by Multiple Intestinal Metastases from a Giant Cell Carcinoma of the Lung: a Case Report.

    PubMed

    Mandeville, Y; de Gheldere, C; Vanclooster, P

    2015-01-01

    Small bowel obstruction (SBO) due to intussusception in adults is a rare condition. Diagnosis at the time of admission is usually challenging. More often than not, a bowel intussusception in adults is secondary to an organic condition, frequently malignancies. Therefore, a surgical approach is indicated most of the times. We report the case of a forty-nine years old lady presenting with a SBO secondary to small bowel metastases with two ileo-ileal intussusceptions, one of which was missed at initial surgical exploration. A giant cell carcinoma of the lung (GCCL) with small bowel metastases was diagnosed subsequently. The case is presented as well as a brief review of literature.

  2. 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

  3. 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.

  4. First Case Report of Metastatic Squamous Cell Carcinoma of Lung Associated with Mounier-Kuhn Syndrome and Review of Literature.

    PubMed

    Ayub, Fatima; Saif, Muhammad W

    2017-06-26

    Mounier-Kuhn syndrome is a relatively rare condition, mostly involving the trachea and main stem bronchi. It is caused either by the atrophy of elastic fibers or faulty fetal development of cartilage and smooth muscles, hence leading to an overall increase in the diameter of lower respiratory tract. No certain etiology was found in the majority of cases reported previously, however, several other connective tissue diseases have also been implicated with the congenital tracheobronchomegaly. One anecdotal case report mentioned the development of lung malignancy in a patient who had previously received external beam radiotherapy. Herein, we report the first case of Mounier-Kuhn syndrome in a 62-year-old male with a recent diagnosis of metastatic squamous cell carcinoma (SCC) of the lung.

  5. Tobacco smoking as a risk factor of bronchioloalveolar carcinoma of the lung: pooled analysis of seven case-control studies in the International Lung Cancer Consortium (ILCCO).

    PubMed

    Boffetta, Paolo; Jayaprakash, Vijayvel; Yang, Ping; Asomaning, Kofi; Muscat, Joshua E; Schwartz, Ann G; Zhang, Zuo-Feng; Le Marchand, Loic; Cote, Michele L; Stoddard, Shawn M; Morgenstern, Hal; Hung, Rayjean J; Christiani, David C

    2011-01-01

    The International Lung Cancer Consortium (ILCCO) was established in 2004, based on the collaboration of research groups leading large molecular epidemiology studies of lung cancer that are ongoing or have been recently completed. This framework offered the opportunity to investigate the role of tobacco smoking in the development of bronchioloalveolar carcinoma (BAC), a rare form of lung cancer. Our pooled data comprised seven case-control studies from the United States, with detailed information on tobacco smoking and histology, which contributed 799 cases of BAC and 15,859 controls. We estimated the odds ratio of BAC for tobacco smoking, using never smokers as a referent category, after adjustment for age, sex, race, and study center. The odds ratio of BAC for ever smoking was 2.47 (95% confidence interval [CI] 2.08, 2.93); the risk increased linearly with duration, amount, and cumulative cigarette smoking and persisted long after smoking cessation. The proportion of BAC cases attributable to smoking was 0.47 (95% CI 0.39, 0.54). This analysis provides a precise estimate of the risk of BAC for tobacco smoking.

  6. TC-99m MIBI SPECT imaging in patients with lung carcinoma: is it a functional probe of multidrug resistance genes?

    PubMed

    Ak, Ilknur; Gülbaş, Zafer; Ocak, Suna; Kaya, Eser; Alataş, Füsun; Vardareli, Erkan; Metintaş, Muzaffer

    2007-01-01

    Multidrug-resistance (MDR) phenotype concerns altered membrane transport that results in lower cell concentrations of cytotoxic drug in many cancer types, including lung cancer, and is related to the overexpression of a variety of proteins that act as adenosine triphosphate-dependent extrusion pumps. Tc-99m Sestamibi (MIBI) is a transport substrate for P-glycoprotein (Pgp) pump. In this study, we assessed the uptake and clearance of technetium-99m-2-hexakis 2-methoxyisobutylisonitrile (Tc-99m MIBI) from the tumor and its correlation with messenger RNA (mRNA) levels of Pgp, MDR-associated protein (MRP1), and lung resistance protein (LRP) in lung carcinoma. This study was carried out on 19 patients (mean age, 60.1 +/- 2.07 years) with advanced-stage lung carcinoma. The tumor samples obtained by bronchoscopy were assessed to estimate the levels of Pgp, MRP1, and LRP expression on mRNA level by quantitative real-time reverse-transcription polymerase chain reaction. Tc-99m MIBI chest imaging was performed 15 and 180 minutes after injection of 740 MBq Tc-99m MIBI. The early (T/Be) and delayed (T/Bd) Tc-99m MIBI uptakes and washout rate (WR) of Tc-99m MIBI from the tumor were measured. No correlation was found between the T/Be Tc-99m MIBI uptake of tumors (T/Be) and the levels of Pgp mRNA, MRP1 mRNA, and LRP mRNA by reverse-transcription polymerase chain reaction. There was a correlation between the mean T/Bd Tc-99m MIBI uptake and Pgp expression of the tumors (P = 0.001, Spearman rho = - 0.702). There was a correlation between the WR of Tc-99m MIBI from the tumor and Pgp expression of the tumor (P = 0.000, Spearman rho = 0.875). Washout rate of Tc-99m MIBI was not related to the levels of MRP1 mRNA (P = 0.93, Spearman rho = 0.02) or LRP mRNA (P = 0.47, Spearman rho = 0.177). Increased WR of Tc-99m MIBI is related in Pgp over expression of the tumor. Tc-99m MIBI single photon emission computed tomography imaging may be a functional probe of overexpression of Pgp in

  7. 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

  8. Lung squamous cell carcinoma with brachial soft tissue metastasis responsive to gefitinib: Report of a rare case

    PubMed Central

    Kataoka, Kana; Osaka, Eiji; Shimizu, Tetsuo; Okamura, Yuki; Yoshida, Yukihiro; Tokuhashi, Yasuaki

    2016-01-01

    Metastasis of lung cancer to soft tissue is rare and patient outcomes are generally poor. There are no reports describing soft tissue metastasis in lung squamous cell carcinoma (SCC), in which gefitinib treatment was effective not only for the primary tumor but also the metastatic lesion. A 61‐year‐old Asian woman presented to our facility with pain and a mass in the brachium. An additional tumor was identified in the lung. As we suspected soft tissue metastasis of lung cancer, an incisional biopsy was performed, yielding a diagnosis of SCC. The brachial tumor continued to grow and became exposed at the biopsy site when the incisional wound dehisced. Because the biopsied specimen was positive for an epidermal growth factor receptor (EGFR) gene mutation, we commenced gefitinib administration. This treatment resulted in the rapid shrinkage of both the brachial metastasis and the primary tumor, followed by healing of the wound. Therefore, tyrosine kinase inhibitors should be used for cases that present EGFR activating mutations independently from the presence of skin and soft tissue metastases. PMID:27755795

  9. 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.

  10. Lung squamous cell carcinoma with brachial soft tissue metastasis responsive to gefitinib: Report of a rare case.

    PubMed

    Kataoka, Kana; Osaka, Eiji; Shimizu, Tetsuo; Okamura, Yuki; Yoshida, Yukihiro; Tokuhashi, Yasuaki

    2016-11-01

    Metastasis of lung cancer to soft tissue is rare and patient outcomes are generally poor. There are no reports describing soft tissue metastasis in lung squamous cell carcinoma (SCC), in which gefitinib treatment was effective not only for the primary tumor but also the metastatic lesion. A 61-year-old Asian woman presented to our facility with pain and a mass in the brachium. An additional tumor was identified in the lung. As we suspected soft tissue metastasis of lung cancer, an incisional biopsy was performed, yielding a diagnosis of SCC. The brachial tumor continued to grow and became exposed at the biopsy site when the incisional wound dehisced. Because the biopsied specimen was positive for an epidermal growth factor receptor (EGFR) gene mutation, we commenced gefitinib administration. This treatment resulted in the rapid shrinkage of both the brachial metastasis and the primary tumor, followed by healing of the wound. Therefore, tyrosine kinase inhibitors should be used for cases that present EGFR activating mutations independently from the presence of skin and soft tissue metastases.

  11. The serum glycoprotein fetuin-A promotes Lewis lung carcinoma tumorigenesis via adhesive-dependent and adhesive-independent mechanisms.

    PubMed

    Kundranda, Madappa N; Henderson, Melodie; Carter, Kathy J; Gorden, Lee; Binhazim, Awadh; Ray, Sanhita; Baptiste, Trevor; Shokrani, Masih; Leite-Browning, Maria L; Jahnen-Dechent, Willi; Matrisian, Lynn M; Ochieng, Josiah

    2005-01-15

    Fetuin-A is a serum glycoprotein in the cystatin family associated with the regulation of soft tissue calcification. We tested the role of systemic fetuin in tumor cell growth and metastasis by injecting Lewis lung carcinoma (LLC) cells into fetuin-A null and their wild-type (WT) littermate control C57BL/6 mice via the tail vein, s.c., and intrasplenic routes. In the experimental metastasis assay, the lungs of the WT mice were filled with metastatic nodules, whereas the lungs of the fetuin-A null mutant mice were virtually free of colonies at the end of 2 weeks. Lung colonization responded to the levels of serum fetuin-A in a dose-dependent manner, as observed by the formation of half as many colonies in mice heterozygous for the fetuin-A locus compared with homozygous WT mice and restoration of lung colonization by the administration of purified fetuin-A to fetuin-A-null mice. Serum fetuin-A also influenced the growth of LLC cells injected s.c.: fetuin-A-null mice developed small s.c. tumors only after a substantial delay. Similarly, intrasplenic injection of LLC cells resulted in rapid colonization of the liver with metastasis to the lungs within 2 weeks in the WT but not fetuin-A null mice. To examine the mechanism by which fetuin-A influences LLC colonization and growth, we showed that LLC tumor cells adhere to fetuin-A in a Ca(2+)-dependent fashion, resulting in growth of the tumor cells. These studies support the role of fetuin-A as a major growth promoter in serum that can influence tumor establishment and growth.

  12. SOX2 expression is associated with FGFR fusion genes and predicts favorable outcome in lung squamous cell carcinomas.

    PubMed

    Zheng, Shanbo; Pan, Yunjian; Wang, Rui; Li, Yuan; Cheng, Chao; Shen, Xuxia; Li, Bin; Zheng, Difan; Sun, Yihua; Chen, Haiquan

    2015-01-01

    SOX2 is a gene that encodes for a transcription factor, which functions as an activator or suppressor of gene transcription. SOX2 amplification and overexpression have been found in various types of tumors and play important roles in cancer cells. The aim of the study was to evaluate SOX2 expression and amplification in lung squamous cell carcinomas (SCCs) and to determine the relationship with main clinicopathologic features, patient prognosis, and common driver mutations. SOX2 protein levels were measured by immunohistochemistry, while SOX2 copy numbers were measured by fluorescence in situ hybridization in resected samples from 162 Chinese lung SCC patients. All patients were also analyzed for mutations in EGFR, HER2, BRAF, PIK3CA, NFE2L2, and FGFR fusion genes. Clinical characteristics, including age, sex, smoking status, stage, relapse-free survival (RFS), and overall survival (OS), were collected. SOX2 overexpression and amplification were observed in 58.6% and 45.9% of lung SCCs. Lung SCC patients with SOX2 overexpression were significantly associated with absence of malignant tumor family history (P=0.021), FGFR fusion gene (P=0.046), longer RFS (P=0.041), and OS (P=0.025). No correlation was found between SOX2 gene amplification and main clinicopathologic features, patient prognosis, or common driver mutations. SOX2 overexpression and amplification are common in lung SCCs. SOX2 over-expression was associated with FGFR fusion genes and predicted favorable outcome in lung SCCs. The underlying relationship of SOX2 and FGFR still needs further investigation.

  13. Ameloblastic carcinoma of the mandible with metastasis to the skull and lung: advanced imaging appearance including computed tomography, magnetic resonance imaging and positron emission tomography computed tomography

    PubMed Central

    Devenney-Cakir, B; Dunfee, B; Subramaniam, R; Sundararajan, D; Mehra, P; Spiegel, J; Sakai, O

    2010-01-01

    Ameloblastic carcinoma is a very rare malignant odontogenic tumour with characteristic histopathological and clinical features, which requires aggressive surgical treatment and surveillance and, therefore, differs from ameloblastoma. Metastasis typically occurs in the lung. Only one patient with metastasis to the skull has previously been described and no prior case reports have presented MRI and positron emission tomography-CT (PET-CT) imaging findings. We describe a case of ameloblastic carcinoma with metastasis to the skull and lung with emphasis on imaging features including MRI and PET-CT. PMID:20841465

  14. Influence of some synthetic antioxidants on the growth and metastases formation of Lewis lung carcinoma and amelanotic B16 melanoma in C57BL mice.

    PubMed

    Kanclerz, A; Zbytniewski, Z; Boeryd, B

    1981-01-01

    Synthetic antioxidants: EPO (p-ethoxyphenol), PHP (p-hydroxypropiophenone), and DPPD (N,N'-diphenyl-p-phenylenediamine) dissolved in dimethylsulfoxide were administered subcutaneously to mice after subcutaneous implantation of Lewis lung carcinoma or amelanotic B16 melanoma into the tails. The doses of antioxidants used were: 50 mg/kg, 100 mg/kg, and 200 mg/kg per day, respectively. The animals received five injections a week during two weeks. The tails with Lewis lung carcinoma were amputated after 16 days and with amelanotic melanoma after 20 days; tumors weight was measured. 25 days after Lewis lung carcinoma and 42 days after B16 melanoma implantation mice were sacrificed, lungs weighed and incidence of pulmonary and extrapulmonary metastases were estimated. There was a significant increase of weight of amelanotic melanoma in animals treated with EOP or PHP (p less than or equal to 0.05). No influence of antioxidants on the metastases incidence of B16 melanoma was found. Antioxidants used did not influence the Lewis lung carcinoma weight, whereas EOP or PHP increased the incidence of extrapulmonary metastases (p = 0.05, and p = 0.1, respectively).

  15. Expression of the WT1 gene -KTS domain isoforms suppresses the invasive ability of human lung squamous cell carcinoma cells.

    PubMed

    Moriya, Shogo; Takiguchi, Masaki; Seki, Naohiko

    2008-02-01

    Although the WT1 gene was originally isolated as a tumor suppressor gene from Wilms' tumor, oncogenic roles for WT1 have been reported in several tumors. Here, we present new findings of high levels of WT1 expression associated with the suppression of lymph node metastasis in patients with human lung squamous cell carcinoma (SCC). We investigated the effect of down-regulated WT1 gene expression on the invasive phenotype of the SCC cell line RERF-LC-AI. Invasive ability was enhanced in WT1-specific siRNA-transfected cells, and a WT1 target gene p21(Waf1/Cip1) was isolated by comprehensive gene expression analysis. As several isoforms are produced from the WT1 gene, we isolated eight major WT1 isoforms from a cDNA library and cloned each variant into an expression vector. Luciferase reporter assays revealed that p21(Waf1/Cip1) expression was enhanced only by the WT1 cDNA variants that included a three-amino acid deletion (-KTS). Our results suggested that the -KTS-containing variants of WT1 are directly involved in the regulation of p21(Waf1/Cip1) expression and the subsequent suppression of lymph node metastasis in human lung squamous cell carcinoma.

  16. 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 Central

    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

  17. 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

    2014-12-10

    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.

  18. Results of multifield conformal radiation therapy of nonsmall-cell lung carcinoma using multileaf collimation beams.

    PubMed

    Bahri, S; Flickinger, J C; Kalend, A M; Deutsch, M; Belani, C P; Sciurba, F C; Luketich, J D; Greenberger, J S

    1999-01-01

    A five-field conformal technique with three-dimensional radiation therapy treatment planning (3-DRTP) has been shown to permit better definition of the target volume for lung cancer, while minimizing the normal tissue volume receiving greater than 50% of the target dose. In an initial study to confirm the safety of conventional doses, we used the five-field conformal 3-DRTP technique. We then used the technique in a second study, enhancing the therapeutic index in a series of 42 patients, as well as to evaluate feasibility, survival outcome, and treatment toxicity. Forty-two consecutive patients with nonsmall-cell lung carcinoma (NSCLC) were evaluated during the years 1993-1997. The median age was 60 years (range 34-80). The median radiation therapy (RT) dose to the gross tumor volume was 6,300 cGy (range 5,000-6,840 cGy) delivered over 6 to 6.5 weeks in 180-275 cGy daily fractions, 5 days per week. There were three patients who received a split course treatment of 5,500 cGy in 20 fractions, delivering 275 cGy daily with a 2-week break built into the treatment course after 10 fractions. The stages of disease were II in 2%, IIIA in 40%, IIIB in 42.9%, and recurrent disease in 14.3% of the patients. The mean tumor volume was 324.14 cc (range 88.3-773.7 cc); 57.1% of the patients received combined chemoradiotherapy, while the others were treated with radiation therapy alone. Of the 42 patients, 7 were excluded from the final analysis because of diagnosis of distant metastasis during treatment. Two of the patients had their histology reinterpreted as being other than NSCLC, 2 patients did not complete RT at the time of analysis, and 1 patient voluntarily discontinued treatment because of progressive deterioration. Median follow-up was 11.2 months (range 3-32.5 months). Survival for patients with Stage III disease was 70.2% at 1 year and 51.5% at 2 years, with median survival not yet reached. Local control for the entire series was 23.3+/-11.4% at 2 years. However, for

  19. Chromosomal Abnormalities in Non-Small Cell Lung Carcinomas and in Bronchial Epithelia of High-Risk Smokers Detected by Multi-Target Interphase Fluorescence in Situ Hybridization

    PubMed Central

    Santos Romeo, Maura; Sokolova, Irina A.; Morrison, Larry E.; Zeng, Chan; Barón, Anna E.; Hirsch, Fred R.; Miller, York E.; Franklin, Wilbur A.; Varella-Garcia, Marileila

    2003-01-01

    Human lung carcinogenesis is accompanied by complex chromosomal changes that may be detected in interphase cells by fluorescence in situ hybridization (FISH) assay using recently developed multitarget DNA probes. Touch preparations of 20 non-small cell lung carcinomas, sputum specimens from 3 patients with lung cancer and from 11 ex-smokers without lung cancer, and cultured benign bronchial epithelium of 42 high-risk smokers, 9 of whom had concurrent invasive carcinoma, were tested using a four-color FISH probe (LAVysion) targeting centromere 6, 5p15.2, 7p12 (EGFR), and 8q24 (MYC). Significantly high frequencies of abnormal cells were found in each of the 20 NSCLC (100%) and in the 3 sputum specimens from lung cancer patients. None of the cytologically normal sputa contained FISH abnormalities. Cultured bronchial epithelial cells from 11 of 42 patients (26%) were abnormal for at least one probe. Abnormal FISH patterns had no association with gender, presence of tumor or histology. Multicolor FISH can readily detect chromosomal abnormalities in imprints and sputa from lung carcinomas. Chromosomal aneusomy is also frequent in bronchial epithelial cells from long-term smokers. The prognostic significance of the multicolor LAVysion FISH probe set should be validated in a controlled clinical trial. PMID:12707375

  20. Chromosomal abnormalities in non-small cell lung carcinomas and in bronchial epithelia of high-risk smokers detected by multi-target interphase fluorescence in situ hybridization.

    PubMed

    Romeo, Maura Santos; Sokolova, Irina A; Morrison, Larry E; Zeng, Chan; Barón, Anna E; Hirsch, Fred R; Miller, York E; Franklin, Wilbur A; Varella-Garcia, Marileila

    2003-05-01

    Human lung carcinogenesis is accompanied by complex chromosomal changes that may be detected in interphase cells by fluorescence in situ hybridization (FISH) assay using recently developed multitarget DNA probes. Touch preparations of 20 non-small cell lung carcinomas, sputum specimens from 3 patients with lung cancer and from 11 ex-smokers without lung cancer, and cultured benign bronchial epithelium of 42 high-risk smokers, 9 of whom had concurrent invasive carcinoma, were tested using a four-color FISH probe (LAVysion) targeting centromere 6, 5p15.2, 7p12 (EGFR), and 8q24 (MYC). Significantly high frequencies of abnormal cells were found in each of the 20 NSCLC (100%) and in the 3 sputum specimens from lung cancer patients. None of the cytologically normal sputa contained FISH abnormalities. Cultured bronchial epithelial cells from 11 of 42 patients (26%) were abnormal for at least one probe. Abnormal FISH patterns had no association with gender, presence of tumor or histology. Multicolor FISH can readily detect chromosomal abnormalities in imprints and sputa from lung carcinomas. Chromosomal aneusomy is also frequent in bronchial epithelial cells from long-term smokers. The prognostic significance of the multicolor LAVysion FISH probe set should be validated in a controlled clinical trial.

  1. Close relation of large cell carcinoma to adenocarcinoma by hierarchical cluster analysis: implications for histologic typing of lung cancer on biopsies.

    PubMed

    Hammer, Stephan H; Prall, Friedrich

    2015-09-01

    Determining histologic types of lung cancer on biopsies can be difficult. This study addresses the role of immunohistochemistry in histologic typing, using a tissue microarray (TMA) as "model biopsies," and presents a classification generated by an unsupervised hierarchical cluster analysis. A TMA was made from resection specimens of a consecutive series of 165 lung tumors. In a "tissue-spot review" with hematoxylin and eosin sections all the large cell carcinomas (N=22) were assigned to the noncommittal class of non-small cell lung cancer (NSCLC), as were an additional 37 tumors of defined histologic types. Adenocarcinomas and squamous cell carcinomas included with these NSCLC could be diagnosed by immunohistochemistry with antibodies against TTF-1, Napsin A, cytokeratin (CK)7, p40, p63, and CK5/6 with moderate to good sensitivities and specificities. Unsupervised hierarchical clustering was done with these data and additional high-molecular-weight cytokeratins, CD56, synaptophysin, and chromogranin immunohistochemistry. This delineated separate clusters for adenocarcinomas, large cell carcinomas, neuroendocrine tumors, and squamous cell carcinomas. Notably, adenocarcinoma and large cell carcinoma clusters were closely related and clearly set off from the squamous cell carcinoma cluster. As would be expected for a clinically well-staged series CDX2, GATA3, estrogen, and progesterone receptor immunohistochemistry remained negative in the vast majority of the tumors and, if positive, were restricted to very few cells. These results, the clustering data in particular, underpin the pragmatic recommendation canvassed with the IASLC/ATS/ERS classification of lung cancers that adenocarcinoma-type molecular studies should include NSCLC with a nonsquamous cell carcinoma immunophenotype.

  2. Renal-cell carcinoma risk estimates based on participants in the prostate, lung, colorectal, and ovarian cancer screening trial and national lung screening trial.

    PubMed

    Lotan, Yair; Karam, Jose A; Shariat, Shahrokh F; Gupta, Amit; Roupret, Morgan; Bensalah, Karim; Margulis, Vitaly

    2016-04-01

    Current knowledge regarding risk of renal-cell carcinoma (RCC) is based on meta-analyses of case-control studies. The Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial and National Lung Screening Trial (NLST) provide robust prospective databases with clinical information and rates of cancer development. PLCO and NLST were used to identify risk factors for RCC. Data were extracted from PLCO and NLST to stratify risk of RCC by sex, race, age at inclusion, obesity, and smoking status. Incidence rates between groups were compared using the chi-square test. We excluded urothelial carcinomas. Overall, 701/154,118 and 190/53,242 RCCs were detected in PLCO and NLST, respectively. Incidence rates were higher in men (PLCO: 0.56 vs. 0.28/1000 person y, NLST: 0.73 vs. 0.35/1000 person y; both with P<0.0001). In the PLCO, male sex, age>60 years, obesity, and intensity of smoking were associated with higher risk of developing RCC. In the NLST, sex and morbid obesity increased the risk for RCC but age, ethnicity, and smoking intensity were not predictors. There was no effect of screening for other cancers on detection of RCC. High-grade (grades ≥3) RCCs were diagnosed in 145 (20.7%) and 60 (31.6%) in the PLCO and NLST. In PLCO, age (60-64y), male sex, obesity, and current smokers with>50 pack years were at increased risk for high-grade RCC. In NLST, only male sex was an independent predictor of high-grade RCC. Age over 60 years, male sex, smoking intensity, and obesity affect the risk of RCC. Identification of a high-risk population may allow a pilot study of rational screening for RCC. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. The Transcriptional Consequences of Somatic Amplifications, Deletions, and Rearrangements in a Human Lung Squamous Cell Carcinoma12

    PubMed Central

    Stead, Lucy F; Berri, Stefano; Wood, Henry M; Egan, Philip; Conway, Caroline; Daly, Catherine; Papagiannopoulos, Kostas; Rabbitts, Pamela

    2012-01-01

    Lung cancer causes more deaths, worldwide, than any other cancer. Several histologic subtypes exist. Currently, there is a dearth of targeted therapies for treating one of the main subtypes: squamous cell carcinoma (SCC). As for many cancers, lung SCC karyotypes are often highly anomalous owing to large somatic structural variants, some of which are seen repeatedly in lung SCC, indicating a potential causal association for genes therein. We chose to characterize a lung SCC genome to unprecedented detail and integrate our findings with the concurrently characterized transcriptome. We aimed to ascertain how somatic structural changes affected gene expression within the cell in ways that could confer a pathogenic phenotype. We sequenced the genomes of a lung SCC cell line (LUDLU-1) and its matched lymphocyte cell line (AGLCL) to more than 50x coverage. We also sequenced the transcriptomes of LUDLU-1 and a normal bronchial epithelium cell line (LIMM-NBE1), resulting in more than 600 million aligned reads per sample, including both coding and non-coding RNA (ncRNA), in a strand-directional manner. We also captured small RNA (<30 bp). We discovered significant, but weak, correlations between copy number and expression for protein-coding genes, antisense transcripts, long intergenic ncRNA, and microRNA (miRNA). We found that miRNA undergo the largest change in overall expression pattern between the normal bronchial epithelium and the tumor cell line. We found evidence of transcription across the novel genomic sequence created from six somatic structural variants. For each part of our integrated analysis, we highlight candidate genes that have undergone the largest expression changes. PMID:23226101

  4. Cisplatin Increases Sensitivity to FGFR Inhibition in Patient-Derived Xenograft Models of Lung Squamous Cell Carcinoma.

    PubMed

    Weeden, Clare E; Holik, Aliaksei Z; Young, Richard J; Ma, Stephen B; Garnier, Jean-Marc; Fox, Stephen B; Antippa, Phillip; Irving, Louis B; Steinfort, Daniel P; Wright, Gavin M; Russell, Prudence A; Ritchie, Matthew E; Burns, Christopher J; Solomon, Benjamin; Asselin-Labat, Marie-Liesse

    2017-08-01

    Lung squamous cell carcinoma (SqCC) is a molecularly complex and genomically unstable disease. No targeted therapy is currently approved for lung SqCC, although potential oncogenic drivers of SqCC have been identified, including amplification of the fibroblast growth factor receptor 1 (FGFR1). Reports from a recently completed clinical trial indicate low response rates in patients treated with FGFR tyrosine kinase inhibitors, suggesting inadequacy of FGFR1 amplification as a biomarker of response, or the need for combination treatment. We aimed to develop accurate models of lung SqCC and determine improved targeted therapies for these tumors. We show that detection of FGFR1 mRNA by RNA in situ hybridization is a better predictor of response to FGFR inhibition than FGFR1 gene amplification using clinically relevant patient-derived xenograft (PDX) models of lung SqCC. FGFR1-overexpressing tumors were observed in all histologic subtypes of non-small cell lung cancers (NSCLC) as assessed on a tissue microarray, indicating a broader range of tumors that may respond to FGFR inhibitors. In FGFR1-overexpressing PDX tumors, we observed increased differentiation and reduced proliferation following FGFR inhibition. Combination therapy with cisplatin was able to increase tumor cell death, and dramatically prolonged animal survival compared to single-agent treatment. Our data suggest that FGFR tyrosine kinase inhibitors can benefit NSCLC patients with FGFR1-overexpressing tumors and provides a rationale for clinical trials combining cisplatin with FGFR inhibitors. Mol Cancer Ther; 16(8); 1610-22. ©2017 AACR. ©2017 American Association for Cancer Research.

  5. CD117, Ki-67, and p53 predict survival in neuroendocrine carcinomas, but not within the subgroup of small cell lung carcinoma.

    PubMed

    Erler, Brian S; Presby, Matthew M; Finch, Meredith; Hodges, Allison; Horowitz, Kari; Topilow, Arthur A; Matulewicz, Theodore

    2011-02-01

    High-grade neuroendocrine carcinomas (NECs) are aggressive tumors with limited treatment options. Recently, studies have observed that the tyrosine kinase receptor CD117 is often overexpressed in this malignancy. As a result, CD117 has been identified as a target for therapy via the small molecule, tyrosine kinase inhibitor imatinib mesylate. In the present study, 17 low-grade, 4 intermediate-grade, and 76 high-grade NECs were immunostained for CD117, Ki-67, and p53. Overexpression of the three markers was mainly, but not exclusively seen in the high-grade NECs. Patients with overexpression of CD117 and p53 and increased Ki-67 expression showed reduced survival. However, no difference in survival was observed when the same analysis was applied solely to small cell lung cancer patients, the largest subset studied. These findings suggest that overexpression of CD117, p53, and Ki-67 reflects tumor grade and predicts survival in NECs, but fail as prognostic markers in the subset of small cell lung cancer patients.

  6. Claudin-5, -7, and -18 suppress proliferation mediated by inhibition of phosphorylation of Akt in human lung squamous cell carcinoma.

    PubMed

    Akizuki, Risa; Shimobaba, Shun; Matsunaga, Toshiyuki; Endo, Satoshi; Ikari, Akira

    2017-02-01

    Abnormal expression of claudin (CLDN) subtypes has been reported in various solid cancers. However, it is unknown which subtype plays a key role in the regulation of proliferation in cancer cells. The expression of CLDN3-5, 7, and 18 in human lung squamous carcinoma tissues was lower than that in normal tissue. Here, we examined which combination of exogenous CLDNs expression inhibits proliferation and the molecular mechanism using human lung squamous RERF-LC-AI cells. Real-time polymerase chain reaction and western blotting showed that CLDN3-5, 7, and 18 are little expressed in RERF-LC-AI cells. In the exogenously transfected cells, CLDN5, 7, and 18 were distributed in the cell-cell contact areas concomitant with ZO-1, a tight junctional scaffolding protein, whereas CLDN3 and 4 were not. Cell proliferation was individually and additively suppressed by CLDN5, 7, and 18. The expression of these CLDNs showed no cytotoxicity compared with mock cells. CLDN5, 7, and 18 increased p21 and decreased cyclin D1, resulting in the suppression of cell cycle G1-S transition. The expression of these CLDNs inhibited phosphorylation of Akt without affecting phosphorylated ERK1/2. Furthermore, these CLDNs inhibited the nuclear localization of Akt and its association with 3-phosphoinositide-dependent protein kinase-1 (PDK1). The suppression of G1-S transition caused by CLDN5, 7, and 18 was rescued by the expression of constitutively active-Akt. We suggest that the reduction of CLDN5, 7, and 18 expression loses the suppressive ability of interaction between PDK1 and Akt and causes sustained phosphorylation of Akt, resulting in the disordered proliferation in lung squamous carcinoma cells.

  7. Screening and identification of distant metastasis-related differentially expressed genes in human squamous cell lung carcinoma.

    PubMed

    Wang, Na; Zhou, Fachen; Xiong, Hai; Du, Sha; Ma, Jianwei; Okai, Issac; Wang, Jian; Suo, Jing; Hao, Lihong; Song, Yang; Hu, Jun; Shao, Shujuan

    2012-05-01

    Distant metastasis is one of the leading causes of lung cancer death. Detecting the early-stage molecular alternations in primary tumors, such as gene expression differences, provides a "prognostic" value to the precaution of tumor metastasis. The aim of this article is to screen and identify the metastasis-related genes in human squamous cell lung carcinoma. Primary tumor tissues of nine patients with subsequent metastasis and eight patients without metastasis were selected to perform the gene microarray experiment. GO and pathway analyses were used to determine the differentially expressed genes. Two identified genes were further validated by real-time quantitative reverse transcription polymerase chain reaction (PCR) (real-time qRT-PCR). Two hundred and thirty-eight differentially expressed genes were detected in gene chip experiment, including 51 up-regulated genes and 187 down-regulated genes. These genes were involved in several cellular processes, including cell adhesion, cell cycle regulation, and apoptosis. GO analysis showed that the differentially expressed genes participated in a wide ranging of metastasis-related processes, including extracellular region and regulation of liquid surface tension. In addition, pathway analysis demonstrated that the differentially expressed genes were enriched in pathways related to cell cycle and Wnt signaling. Real-time qRT-PCR validation experiment of LCN2 and PDZK1IP1 showed a consistent up-regulation in the metastasis group. The metastasis of human squamous cell lung carcinoma is a complex process that is regulated by multiple gene alternations on the expression levels. The 238 differentially expressed genes identified in this study presumably contain a core set of genes involved in tumor metastasis. The real-time qRT-PCR results of PDZK1IP1 and LCN2 validated the reliability of this gene microarray experiment.

  8. Fundamental principals of tumor necrosis factor-alpha gene therapy approach and implications for patients with lung carcinoma.

    PubMed

    Sanlioglu, Ahter D; Aydin, Cigdem; Bozcuk, Hakan; Terzioglu, Ender; Sanlioglu, Salih

    2004-05-01

    Apoptosis, known as programmed cell death, is defined as a cell's preferred form of death under hectic conditions through genetically conserved and complex pathways. There is a decisive balance between stimulatory and inhibitory signaling pathways to maintain homeostasis in cells. In order to shift the balance towards apoptosis, the modulation of both apoptotic and anti-apoptotic pathways represents an attractive target for cancer therapeutics. Currently, chemotherapy and radiotherapy are among the most commonly used treatment modalities against lung cancer. Tumor suppressor gene, p53, is required in order for both of these treatment methods to work as anti-tumor agents. As a result, tumors lacking p53 display resistance to both chemotherapy and radiotherapy. However, death ligands induce apoptosis regardless of p53 status of cells. Thus, these methods constitute a complementary therapeutic approach to currently employed conventional treatment modalities. At present, death ligands are being evaluated as potential cancer therapeutic agents. Since resistance to tumor necrosis factor (TNF)-alpha-mediated apoptosis represented an obstacle for the treatment of patients with lung carcinoma in the earlier attempts, an extensive research was recently initiated to understand molecular mechanism of TNF-alpha signaling. NF-kappaB transcription factors have been demonstrated to modulate the apoptotic program, mostly as blockers of apoptosis in different cell types. In this review, we concentrate on the current progress in the understanding of TNF-alpha-mediated apoptosis for lung carcinoma. Representative models of NF-kappaB-inhibiting gene therapy strategies from various labs including ours are also provided as examples of up-to-date approaches to defeat TNF resistance. In order to give the reader better understanding and appreciation of such approaches, previously unpublished in vivo assays are also incorporated into this review. Current progress in clinical trials using

  9. 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. Copyright © 2016. Published by Elsevier B.V.

  10. Effect of Thoracic Radiotherapy Timing and Fractionation on Survival in Nonmetastatic Small Cell Lung Carcinoma.

    PubMed

    Wong, Andrew T; Rineer, Justin; Schwartz, David; Becker, Daniel; Safdieh, Joseph; Osborn, Virginia; Schreiber, David

    2017-03-01

    The optimal timing of thoracic radiation therapy (RT) in relation to chemotherapy is unknown in the treatment of nonmetastatic small cell lung cancer (SCLC). We analyzed the National Cancer Data Base (NCDB) to assess the effect on overall survival (OS) of RT timing with chemotherapy for patients with SCLC. The NCDB was queried for patients diagnosed with nonmetastatic SCLC from 1998 to 2011 who had undergone definitive chemoradiation. The patients were stratified into quartiles according to the interval between the start of chemotherapy and the start of RT. The first and second quartiles (RT started 0-20 days after chemotherapy) were classified as "early" RT and the third and fourth quartiles (RT started 21-126 days after chemotherapy) as "late" RT. Patients were included if they had received hyperfractionated 45 Gy in 30 fractions or standard fractionation of ≥ 60 Gy in 1.8- to 2-Gy fractions. Kaplan-Meier analyses of OS were performed, and multivariable Cox regression analysis was conducted to assess the effect of the covariates on OS. A total of 8391 patients were included (50.5% had received early RT). Early RT was associated with significant improvement in survival (5-year OS, 21.9% vs. 19.1%; P = .01). On subgroup analysis, the survival advantage for early RT was significant for patients receiving hyperfractionated RT (5-year OS, 28.2% vs. 21.2%; P = .004) but not for those receiving standard fractionation (19.8% vs. 18.4%; P = .29). On multivariable Cox regression analysis, hyperfractionated RT was associated with reduced mortality (hazard ratio [HR], 0.90; 95% confidence interval [CI], 0.85-0.96; P = .001), but early RT was not (HR, 0.98; 95% CI, 0.94-1.04; P = .53). These data support the early initiation of hyperfractionated thoracic RT for nonmetastatic SCLC. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Long-term disease-free survivor of metastatic large-cell neuroendocrine carcinoma of the lung treated with amrubicin and irinotecan

    PubMed Central

    Ryuge, Shinichiro; Jiang, Shi-Xu; Wada, Mayuko; Katono, Ken; Iwasaki, Maiko; Takakura, Akira; Otani, Sakiko; Kimura, Yuka; Fukui, Tomoya; Yokoba, Masanori; Kubota, Masaru; Katagiri, Masato; Hayakawa, Kazusige; Masuda, Noriyuki

    2009-01-01

    Large-cell neuroendocrine carcinoma (LCNEC) is a relatively uncommon variant of non-small cell lung cancer. Since the biological characteristics of LCNEC are similar to those of small cell lung cancer, LCNEC is usually treated with chemotherapy regimens used for small cell lung cancer. However, the outcomes are usually dismal. Here, we report a patient with LCNEC (a metastasis to the brain). After whole brain irradiation, he received a combination of amrubicin and irinotecan chemotherapy, and has been relapse-free for two years. This treatment regimen may be beneficial for patients with advanced LCNEC. PMID:19920936

  12. 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.

  13. 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

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

    PubMed

    Beltran, Adriana S; Blancafort, Pilar

    2011-02-01

    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 thus, represent novel therapeutic agents for metastatic lung cancers.

  15. Meat consumption and risk of squamous cell carcinoma of the lung: a case-control study in Uruguayan men.

    PubMed

    Deneo-Pellegrini, Hugo; Ronco, Alvaro L; De Stefani, Eduardo

    2015-01-01

    In the period 1995-2004, a hospital-based case-control study on meat consumption and squamous cell carcinoma of the lung in men was conducted in Montevideo, Uruguay. The study included 300 cases and 600 controls, frequency matched on age and residence. The results showed that total meat [odds ratio (OR) = 1.72, 95% confidence interval (CI): 1.05-2.81, P value for trend = 0.03], red meat (OR = 1.82, 95% CI: 1.13-2.91, P value for trend = 0.01), beef consumption (OR = 2.22, 95% CI: 1.42-3.45, P value for trend = 0.0004), bacon (OR = 1.50, 95% CI: 1.00-2.24, P value for trend = 0.03), saucisson (OR = 1.69, 95% CI: 1.07-2.67, P value for trend = 0.01), and salted meat intake (OR = 2.70, 95% CI: 1.63-4.46, P value for trend = 0.0001) were positively associated with squamous cell lung cancer. These results are discussed and we suggest that meat consumption could be considered as a strong risk factor for squamous cell lung cancer.

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

    USDA-ARS?s Scientific Manuscript database

    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 ...

  17. [Cytogenetic features of the differential diagnosis of lymphoid thymomas, small-cell non-Hodgkin lymphomas and undifferentiated small cell lung carcinoma].

    PubMed

    Alekseenko, O I

    2004-01-01

    The predominance of compact and nucleolonemic types of nucleoli in undifferentiated small cell carcinoma of lung, the prevalence of micronucleoli and ring-shaped types of nucleoli in lymphoid thymoma and the increase of the level of micronucleoli in small cell non-Hodgkin's lymphoma have been established.

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

    USDA-ARS?s Scientific Manuscript database

    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...

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

    USDA-ARS?s Scientific Manuscript database

    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...

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

    USDA-ARS?s Scientific Manuscript database

    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...

  1. 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

  2. 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

  3. Reirradiation for locoregionally recurrent lung cancer: outcomes in small cell and non-small cell lung carcinoma.

    PubMed

    Kruser, Tim J; McCabe, Bradley P; Mehta, Minesh P; Khuntia, Deepak; Campbell, Toby C; Geye, Heather M; Cannon, George M

    2014-02-01

    To our knowledge this is the largest report analyzing outcomes for re-irradiation (reRT) for locoregionally recurrent lung cancer, and the first to assess thoracic reRT outcomes in patients with small cell lung cancer (SCLC). Forty-eight patients (11 SCLC, 37 non-small cell lung cancer [NSCLC]) receiving reRT to the thorax were identified; 44 (92%) received reRT by intensity-modulated radiotherapy. Palliative responses, survival outcomes, and prognostic factors were analyzed. NSCLC patients received a median of 30 Gy in a median of 10 fractions, whereas SCLC patients received a median of 37.5 Gy in a median of 15 fractions. Median survival for the entire cohort from reRT was 4.2 months. Median survival for NSCLC patients was 5.1 months, versus 3.1 months for the SCLC patients (P=0.15). In NSCLC patients, multivariate analysis demonstrated that Karnofsky performance status≥80 and higher radiation dose were associated with improved survival following reRT, and 75% of patients with symptoms experienced palliative benefit. In SCLC, 4 patients treated with the intent of life prolongation for radiographic recurrence had a median survival of 11.7 months. However, acute toxicities and new disease symptoms limited the duration of palliative benefit in the 7 symptomatic SCLC patients to 0.5 months. ReRT to the thorax for locoregionally recurrent NSCLC can provide palliative benefit, and a small subset of patients may experience long-term survival. Select SCLC patients may experience meaningful survival prolongation after reRT, but reRT for patients with symptomatic recurrence and/or extrathoracic disease did not offer meaningful survival or durable symptom benefit.

  4. Prevalence, morphology, and natural history of FGFR1-amplified lung cancer, including squamous cell carcinoma, detected by FISH and SISH.

    PubMed

    Russell, Prudence A; Yu, Yong; Young, Richard J; Conron, Matthew; Wainer, Zoe; Alam, Naveed; Solomon, Benjamin; Wright, Gavin M

    2014-12-01

    The aim of this study was to investigate the prevalence of fibroblast growth factor receptor 1 (FGFR1) amplification by fluorescence in situ hybridization (FISH) in a lung cancer patient cohort and to correlate results with morphology, silver in situ hybridization (SISH), and patient outcome. FGFR1 FISH and SISH were performed in 406 and 385 lung cancer cases, respectively, and the results were compared. High-level FGFR1 amplification was defined as the ratio of FGFR1/centromere 8 ≥2, or tumor cell percentage with ≥15 signals ≥10%, or average number of signals/tumor cell nucleus ≥6. Low-level amplification was defined as tumor cell percentage with ≥5 signals ≥50%. Of 406 tumors tested, there were 191 squamous cell carcinomas, 28 carcinomas with focal squamous morphology, 24 large cell carcinomas with squamous immunoprofile, 115 adenocarcinomas, 17 neuroendocrine tumors, and 31 carcinomas without squamous morphology or immunoprofile. FGFR1 FISH was assessable in 368 tumors, with FGFR1 amplification identified in 50, including 48 tumors with either squamous morphology or immunoprofile (48 of 225, 21.3%), and two 'marker-null' tumors without squamous or glandular morphology or immunoprofile (2 of 143, 1.4%; P<0.0001). FGFR1 SISH was assessable in 347 tumors. All 46 FGFR1 FISH-amplified tumors with tumor available for testing showed amplification with SISH, while all other tumors were negative. There was no relationship between FGFR1 amplification status and disease-free (P=0.88, HR=1.04, 95% confidence interval (CI)=0.67-1.60) or overall survival (P=0.97, HR=1.01, 95% CI=0.65-1.58) in surgically radically treated patients with tumors with any squamous morphology or immunoprofile. FGFR1 amplification is a common abnormality in tumors with any squamous morphology or immunoprofile, but it is also present in 'marker-null' tumors. The results of FGFR1 SISH showed 1:1 correlation with the results of FGFR1 FISH, indicating that SISH may be an alternative method

  5. Three-dimensional conformal radiotherapy for locoregionally recurrent lung carcinoma after external beam irradiation: a prospective phase I-II clinical trial.

    PubMed

    Wu, Kai-Liang; Jiang, Guo-Liang; Qian, Hao; Wang, Li-Juan; Yang, Huan-Jun; Fu, Xiao-Long; Zhao, Shen

    2003-12-01

    To observe in a clinical trial the feasibility, tolerance, and efficacy of reirradiation by three-dimensional conformal radiotherapy (3D-CRT) for locoregionally recurrent lung carcinoma after external beam radiotherapy (EBRT). Between June 1999 and March 2001, 23 lung carcinoma patients with locoregional recurrence after EBRT were enrolled in this study. Of the 23 patients, 21 were men and 2 were women (median age 68 years, range 43-79). At the first course of RT, 9 patients had squamous cell carcinoma, 7 adenocarcinoma, and 7 small cell carcinoma. The interval between the first course of RT and recurrence varied from 6 to 42 months (median 13). The median dose of the first course of RT was 66 Gy (range 30-78). Reirradiation was carried out using 3D-CRT and only covered the radiographic lesions. The median dose of reirradiation was 51 Gy (range 46-60), which was delivered by a conventionally fractionated schedule (i.e., 1.8-2.0 Gy/fraction, 5 fractions/wk). The toxicity was assessed according to the Radiation Therapy Oncology Group criteria. The median follow-up time was 15 months (range 2-37). Acute radiation esophagitis occurred in 9% of patients (Grade 1-2). Acute radiation pneumonitis developed in 22% of patients (Grade 1-2). No cases of acute Grade 3 or greater toxicity had been recorded at last follow-up. Pulmonary fibrosis was observed in 26% of patients (Grade 2-3); no other severe late complications have been observed. The 1- and 2-year survival rate was 59% and 21%, respectively. The locoregional progression-free rate at 1 and 2 years was 51% and 42%, respectively. Reirradiation using 3D-CRT was tolerated by this group of recurrent lung carcinoma patients without severe complications. The 2-year outcome was encouraging. Reirradiation with 3D-CRT can be considered an option for the management of locoregionally recurrent lung carcinoma.

  6. Evasion mechanisms to tumor necrosis factor alpha (TNF-alpha) of small cell lung carcinoma and non-small cell lung carcinoma cell lines: comparison with the erythroleukaemia K-562 cell line.

    PubMed

    López-González, J S; Hernández García, A; Noyola, M I; Cázares, D A; Mandoki, J J; Morales, F M; Mendieta, I C; Caloca, J V

    2000-03-01

    The tumour necrosis factor alpha (TNF-alpha) is produced by mononuclear phagocytes as a defence mechanism against malignant cells. However, these cells can evade destruction by TNF-alpha. The present study evaluates in three lung cancer cell lines (small cell carcinoma NCI-H69, adenocarcinoma A-427, squamous carcinoma SK-MES-1) and one erythroleukaemia (K-562) cell line the following evasion mechanisms: (1) inhibition of TNF-alpha production, in indirect and direct co-cultures with monocytes; (2) the expression of type I and type II receptors for TNF-alpha (TNFRI and TNFRII) by tumour cell lines, using indirect immunofluorescence and flow cytometry; (3) the sensitivity of tumour cell lines to the toxic action of recombinant human TNF-alpha (rhTNF-alpha). With the exception of cell line NCI-H69, the other tumour cell lines liberated soluble factors that inhibited TNF-alpha production in monocytes. This effect occurred even after membrane contact with the A-427 and SK-MES-1 cell lines. Erythroleukaemia K-562 cells expressed both types of receptors for TNF-alpha, whereas the NCI-H69 cells expressed only TNFRI, and the A-427 and SK-MES-1 cells expressed no receptors. Lines NCI-H69, A-427 and K-562 were insensitive to the cytotoxic action of rhTNF-alpha. In conclusion, different lung cancer cell lines may evade destruction by TNF-alpha by various mechanisms that range from blocking TNF-alpha production by monocytes to blocking the cytotoxic action of this molecule. For selecting the most effective immunotherapy, knowledge of the evasion mechanisms would be useful.

  7. 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.

  8. Bioinformatics analyses of the differences between lung adenocarcinoma and squamous cell carcinoma using The Cancer Genome Atlas expression data.

    PubMed

    Sun, Fenghao; Yang, Xiaodong; Jin, Yulin; Chen, Li; Wang, Lin; Shi, Mengkun; Zhan, Cheng; Shi, Yu; Wang, Qun

    2017-07-01

    The present study aimed to explore gene and microRNA (miRNA) expression differences between lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) were identified by analyzing mRNA and miRNA expression data in normal and cancerous lung tissues that were obtained from The Cancer Genome Atlas database. A total of 778 DEGs and 7 DEMs were identified. Altered gene functions and signaling pathways were investigated using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses, which revealed that DEGs were significantly enriched in extracellular matrix organization, cell differentiation, negative regulation of toll signaling pathway, and several other terms and pathways. Transcription factor (TF)‑miRNA‑gene networks in LUAD and LUSC were predicted using the TargetScan, Miranda, and TRANSFAC databases, which revealed the regulatory links among the TFs, DEMs, and DEGs. The central TFs, i.e., the TFs in the middle of the TF‑miRNA‑gene network, of LUAD and LUSC were similar. Although LUAD and LUSC shared similar miRNAs in the predicted networks, miR‑29b‑3p was demonstrated to be upregulated only in LUAD, whereas miR‑1, miR‑105‑5p, and miR‑193b‑5p were altered in LUSC. These findings may improve our understanding of the different molecular mechanisms in non‑small cell lung cancers and may promote new and accurate strategies for prevention, diagnosis, and treatment.

  9. Immunophenotypic features of metastatic lymph node tumors to predict recurrence in N2 lung squamous cell carcinoma

    PubMed Central

    Matsuwaki, Rie; Ishii, Genichiro; Zenke, Yoshitaka; Neri, Shinya; Aokage, Keiju; Hishida, Tomoyuki; Yoshida, Junji; Fujii, Satoshi; Kondo, Haruhiko; Goya, Tomoyuki; Nagai, Kanji; Ochiai, Atsushi

    2014-01-01

    Patients with mediastinal lymph node metastasis (N2) in squamous cell carcinoma (SqCC) of the lung have poor prognosis after surgical resection of the primary tumor. The aim of this study was to clarify predictive factors of the recurrence of pathological lung SqCC with N2 focusing on the biological characteristics of both cancer cells and cancer-associated fibroblasts (CAFs) in primary and metastatic lymph node tumors. We selected 64 patients with pathological primary lung N2 SqCC who underwent surgical complete resection and investigated the expressions of four epithelial–mesenchymal transition-related markers (caveolin, clusterin, E-cadherin, ZEB2), three cancer stem cell-related markers (ALDH-1, CD44 variant6, podoplanin) of cancer cells, and four markers of CAFs (caveolin, CD90, clusterin, podoplanin) in both primary and matched metastatic lymph node tumors in the N2 area. In the primary tumors, the expressions of all the examined molecules were not related to recurrence. However, in the metastatic lymph node tumors, high clusterin and ZEB2 expressions in the cancer cells and high podoplanin expression in the CAFs were significantly correlated with recurrence (P = 0.03, 0.04, and 0.007, respectively). In a multivariate analysis, only podoplanin expression in the CAFs in metastatic lymph node tumors was identified as a significantly independent predictive factor of recurrence (P = 0.03). Our study indicated that the immunophenotypes of both cancer cells and CAFs in metastatic lymph node tumors, but not primary tumors, provide useful information for predicting the recurrence of pathological N2 lung SqCC. PMID:24814677

  10. Aloe-emodin induced DNA damage through generation of reactive oxygen species in human lung carcinoma cells.

    PubMed

    Lee, Hong-Zin; Lin, Ching-Ju; Yang, Wen-Hui; Leung, Wing-Cheung; Chang, Shen-Pen

    2006-07-28

    The DNA aggregation was found in aloe-emodin-induced H460 cell apoptosis in this study. Aloe-emodin (40microM)-induced DNA single strand breaks were observed by comet assay. Aloe-emodin induced decreases in the mRNA of DNA repair enzymes such as hMTH1, hOGG1 and APE. Although the activity of the radical-scavenging enzyme SOD was enhanced by aloe-emodin, the effects of aloe-emodin on H460 cell apoptosis were suspected to result from the prooxidant. These results suggest that aloe-emodin induced DNA damage through generation of reactive oxygen species in human lung carcinoma cells.

  11. Mucoepidermoid carcinoma of the lung arising at the primary site of a bronchogenic cyst: clinical, cytogenetic, and molecular findings.

    PubMed

    Brassesco, María Sol; Valera, Elvis Terci; Lira, Régia Caroline Peixoto; Torres, Lídia Alice Gomes M; Scrideli, Carlos Alberto; Elias, Jorge; Teixeira, Sara Reis; Tone, Luiz Gonzaga

    2011-02-01

    Primary lung tumors are rare in children, and mucoepidermoid carcinoma (MEC) represents less than 10% of them. Additionally, MEC arising from bronchogenic cysts (BC) is particularly unusual. We describe the clinical and genetic findings on a MEC occurring within a previous location of a BC in an adolescent. This particular association has not been previously reported. The lesion revealed normal karyotype without the typical t(11;19)(q21;p13) translocation. Cyclin D1 overexpression (165-fold increase) was demonstrated by real-time PCR although FISH assessment showed normal hybridization at 11q13. Information on these unusual clinical presentations may present relevant insight on tumorigenesis of infrequent pediatric pulmonary tumors.

  12. [Ginsenoside Rg3 induces apoptosis of human lung squamous cell carcinoma SK-MES-1 cell line].

    PubMed

    Wang, Xin; Zheng, Yu-ling; Li, Ke; Lin, Na; Fan, Qing-xia

    2009-09-01

    To investigate the effect of ginsenoside Rg3 on the apoptosis and survivin expression in human lung squamous cell carcinoma cell line SK-MES-1. SK-MES-1 cells were divided into Rg3 treatment group, blank control group and positive control (arsenic trioxide) group. The apoptotic rate of the cells in each group was determined using flow cytometry, and the expression of survivin protein and mRNA was detected by immunocytochemistry and RT-PCR, respectively. A 48-h treatment with Ginsenoside Rg3 induced increased apoptotic rate of SK-MES-1 cells in a dose-dependent manner. Ginsenoside Rg3 significantly downregulated the expressions of survivin protein and mRNA as compared with the expression levels in the blank control group (P<0.05). Ginsenoside Rg3 can induce the apoptosis of SK-MES-1 cells, the mechanism of which may involve inhibited survivin expression.

  13. Phenotypic modification of human glioma and non-small cell lung carcinoma by glucocorticoids and other agents.

    PubMed

    McLean, J S; Frame, M C; Freshney, R I; Vaughan, P F; Mackie, A E; Singer, I

    1986-01-01

    Glucocorticoids are cytostatic for human glioma grown at a high cell density in cell culture. The effect is not cytotoxic, appears to involve a modification of the cell surface, and has been detected with methyl prednisolone, dexamethasone, and beta-methasone. Glucocorticoids were also found to reduce malignancy-associated properties (plasminogen activator and endothelial mitogenesis) and enhance differentiation (glutamyl synthetase activity and high affinity GABA uptake). Cytostasis was also seen at high cell densities in non-small cell lung carcinoma with a concomitant reduction in plasminogen activator activity and endothelial mitogenesis. Preliminary data on surfactant production in A549 cells suggests that the repression of malignancy-associated properties is accompanied by an increase in cell differentiation. Treatment of the WIL adenocarcinoma gown as a xenograft in nude mice caused total cessation of growth and massive central necrosis in the tumor.

  14. 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.

  15. Critical role of VCP/p97 in the pathogenesis and progression of non-small cell lung carcinoma.

    PubMed

    Valle, Christopher W; Min, Taehong; Bodas, Manish; Mazur, Steven; Begum, Shahnaz; Tang, Danni; Vij, Neeraj

    2011-01-01

    Valosin-containing protein (VCP)/p97 is an AAA ATPase molecular chaperone that regulates vital cellular functions and protein-processing. A recent study indicated that VCP expression levels are correlated with prognosis and progression of non-small cell lung carcinoma (NSCLC). We not only verified these findings but also identified the specific role of VCP in NSCLC pathogenesis and progression. Our results show that VCP is significantly overexpressed in non-small cell lung carcinoma (NSCLC) as compared to normal tissues and cell lines (p<0.001). Moreover, we observed the corresponding accumulation of ubiquitinated-proteins in NSCLC cell lines and tissues as compared to the normal controls. VCP inhibition by si/shRNA or small-molecule (Eeyarestatin I, EerI) significantly (p<0.05, p<0.00007) suppressed H1299 proliferation and migration but induced (p<0.00001) apoptosis. Cell cycle analysis by flow cytometry verified this data and shows that VCP inhibition significantly (p<0.001, p<0.003) induced cell cycle arrest in the G0/G1 phases. We also found that VCP directly regulates p53 and NFκB protein levels as a potential mechanism to control tumor cell proliferation and progression. Finally, we evaluated the therapeutic potential of VCP inhibition and observed significantly reduced NSCLC tumor growth in both in vitro and xenograft murine (athymic-nude) models after EerI treatment (p<0.05). Thus, targeting VCP in NSCLC may provide a novel strategy to restore p53 and NFκB levels and ameliorate the growth and tumorigenicity, leading to improved clinical outcomes. © 2011 Valle et al.

  16. Critical Role of VCP/p97 in the Pathogenesis and Progression of Non-Small Cell Lung Carcinoma

    PubMed Central

    Valle, Christopher W.; Min, Taehong; Bodas, Manish; Mazur, Steven; Begum, Shahnaz; Tang, Danni; Vij, Neeraj

    2011-01-01

    Background Valosin-containing protein (VCP)/p97 is an AAA ATPase molecular chaperone that regulates vital cellular functions and protein-processing. A recent study indicated that VCP expression levels are correlated with prognosis and progression of non-small cell lung carcinoma (NSCLC). We not only verified these findings but also identified the specific role of VCP in NSCLC pathogenesis and progression. Methodology/Principal Findings Our results show that VCP is significantly overexpressed in non-small cell lung carcinoma (NSCLC) as compared to normal tissues and cell lines (p<0.001). Moreover, we observed the corresponding accumulation of ubiquitinated-proteins in NSCLC cell lines and tissues as compared to the normal controls. VCP inhibition by si/shRNA or small-molecule (Eeyarestatin I, EerI) significantly (p<0.05, p<0.00007) suppressed H1299 proliferation and migration but induced (p<0.00001) apoptosis. Cell cycle analysis by flow cytometry verified this data and shows that VCP inhibition significantly (p<0.001, p<0.003) induced cell cycle arrest in the G0/G1 phases. We also found that VCP directly regulates p53 and NFκB protein levels as a potential mechanism to control tumor cell proliferation and progression. Finally, we evaluated the therapeutic potential of VCP inhibition and observed significantly reduced NSCLC tumor growth in both in vitro and xenograft murine (athymic-nude) models after EerI treatment (p<0.05). Conclusions/Significance Thus, targeting VCP in NSCLC may provide a novel strategy to restore p53 and NFκB levels and ameliorate the growth and tumorigenicity, leading to improved clinical outcomes. PMID:22216170

  17. [Benefits of cisplatin-based polychemotherapy in non-small cell bronchogenic carcinoma. Kyushu Lung Cancer Chemotherapy Study Group].

    PubMed

    Ohta, M; Hara, N; Ichikawa, Y; Kanda, T; Shima, K; Tamura, K; Hokama, M

    1988-06-01

    We studied the efficacy of cisplatin-based polychemotherapy for non-small-cell lung cancer. One hundred nineteen patients with adenocarcinoma or large cell carcinoma were randomized to receive cyclophosphamide, adriamycin, cisplatin and mitomycin C (CAPM) or mitomycin C, cytosine arabinoside and tegafur (MCT), and 48 patients with squamous cell carcinoma were randomized to receive cisplatin, adriamycin and peplomycin (PAP) or mitomycin C, cyclophosphamide, tespamine, toyomycin and tegafur (MCTTT). Radiation was given to the chest in patients with stage I-III disease. The response rates were CAPM, 34.5%; MCT, 13.1% (p less than 0.01) and PAP, 63.3%; MCTTT, 42.3%. A significant difference in response rate between the CAPM and MCT regimens was observed only in stage IV patients and not in stage I-III patients. The median survival was 9.5 months in the CAPM arm vs. 6.5 months in the MCT arm (p less than 0.007), and 8.5 months in the PAP arm vs. 6.5 months in the MCTTT arm. Improved median survival for the CAPM regimen was noted only in stage IV patients and not in stage I-III patients when compared to patients given the MCT regimen, respectively. Nausea and vomiting were significantly increased in patients with cisplatin-based polychemotherapy. Myelosuppression was more severe with the CAPM regimen than with the other chemotherapy regimens. We concluded that cisplatin-based polychemotherapy, CAPM and PAP therapy were of more benefit to patients with disseminated non-small-cell lung cancer than MCT and MCTTT therapy.

  18. 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 ...

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

    PubMed Central

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

    2016-01-01

    Lung cancer remains the leading cancer killer around the world. It’s crucial to identify newer mechanism-based targets to effectively manage lung cancer. Annexin A5 (ANXA5) is a protein kinase C inhibitory protein and calcium dependent phospholipid-binding protein, which may act as an endogenous regulator of various pathophysiological processes. However, its molecular mechanism in lung cancer remains poorly understood. This study was designed to determine the mechanism of ANXA5 in lung cancer with a hope to obtain useful information to provide a new therapeutic target. We used a stable isotope dimethyl labeling based quantitative proteomic method to identify differentially expressed proteins in NSCLC cell lines after ANXA5 transfection. Out of 314 proteins, we identified 26 and 44 proteins that were down- and up-regulated upon ANXA5 modulation, respectively. The IPA analysis revealed that glycolysis and gluconeogenesis were the predominant pathways modulated by ANXA5. Multiple central nodes, namely HSPA5, FN1, PDIA6, ENO1, ALDOA, JUP and KRT6A appeared to occupy regulatory nodes in the protein-protein networks upon ANXA5 modulation. Taken together, ANXA5 appears to have pleotropic effects, as it modulates multiple key signaling pathways, supporting the potential usefulness of ANXA5 as a potential target in lung cancer. This study might provide a new insight into the mechanism of ANXA5 in lung cancer. PMID:27684953

  20. Limits and potential of targeted sequencing analysis of liquid biopsy in patients with lung and colon carcinoma.

    PubMed

    Rachiglio, Anna Maria; Esposito Abate, Riziero; Sacco, Alessandra; Pasquale, Raffaella; Fenizia, Francesca; Lambiase, Matilde; Morabito, Alessandro; Montanino, Agnese; Rocco, Gaetano; Romano, Carmen; Nappi, Anna; Iaffaioli, Rosario Vincenzo; Tatangelo, Fabiana; Botti, Gerardo; Ciardiello, Fortunato; Maiello, Monica R; De Luca, Antonella; Normanno, Nicola

    2016-10-11

    The circulating free tumor DNA (ctDNA) represents an alternative, minimally invasive source of tumor DNA for molecular profiling. Targeted sequencing with next generation sequencing (NGS) can assess hundred mutations starting from a low DNA input. We performed NGS analysis of ctDNA from 44 patients with metastatic non-small-cell lung carcinoma (NSCLC) and 35 patients with metastatic colorectal carcinoma (CRC). NGS detected EGFR mutations in 17/22 plasma samples from EGFR-mutant NSCLC patients (sensitivity 77.3%). The concordance rate between tissue and plasma in NSCLC was much lower for other mutations such as KRAS that, based on the allelic frequency and the fraction of neoplastic cells, were likely to be sub-clonal. NGS also identified EGFR mutations in plasma samples from two patients with EGFR wild type tumor tissue. Both mutations were confirmed by droplet digital PCR (ddPCR) in both plasma and tissue samples. In CRC, the sensitivity of the NGS plasma analysis for RAS mutations was 100% (6/6) in patients that had not resection of the primary tumor before blood drawing, and 46.2% (6/13) in patients with primary tumor resected before enrollment. Our study showed that NGS is a suitable method for plasma testing. However, its clinical sensitivity is significantly affected by the presence of the primary tumor and by the heterogeneity of driver mutations.

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

    ClinicalTrials.gov

    2016-12-12

    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

  2. Inhibitory effects of silibinin on proliferation and lung metastasis of human high metastasis cell line of salivary gland adenoid cystic carcinoma via autophagy induction

    PubMed Central

    Jiang, Canhua; Jin, Shufang; Jiang, Zhisheng; Wang, Jie

    2016-01-01

    Objective To investigate the possible mechanisms and effects of silibinin (SIL) on the proliferation and lung metastasis of human lung high metastasis cell line of salivary gland adenoid cystic carcinoma (ACC-M). Methods A methyl thiazolyl tetrazolium assay was performed to detect the inhibitory effects of SIL on the proliferation of ACC-M cells in vitro. Fluorescence microscopy and transmission electron microscopy were used to observe the autophagic process. Western blot was performed to detect the expression of microtube-related protein 1 light-chain 3 (LC3). An experimental adenoid cystic carcinoma (ACC) lung metastasis model was established in nude mice to detect the impacts of SIL on lung weight and lung cancer nodules. Immunohistochemistry was used to detect the expressions of LC3 in human ACC samples and normal salivary gland tissue samples. Results SIL inhibited the proliferation of ACC-M cells in a dose- and time-dependent manner, and inductively increased the autophagic bodies in ACC-M cells. Furthermore, SIL could increase the expression of LC3 in ACC-M cells and promote the conversion of LC3-I into LC3-II in a dose- and time-dependent manner. In the ACC lung metastasis model, the lung weight and left and right lung nodules in the SIL-treated group were significantly less than those in the control group (P<0.05). The expressions of LC3-I and LC3-II as well as the positive expression rate of LC3 (80%) significantly increased, but the positive expression of LC3 in human ACC (42.22%) reduced significantly. Conclusion SIL could inhibit the proliferation and lung metastasis of ACC-M cells by possibly inducing tumor cells autophagy. PMID:27822066

  3. Enhanced DNA double-strand break repair of microbeam targeted A549 lung carcinoma cells by adjacent WI38 normal lung fibroblast cells via bi-directional signaling.

    PubMed

    Kobayashi, Alisa; Tengku Ahmad, Tengku Ahbrizal Farizal; Autsavapromporn, Narongchai; Oikawa, Masakazu; Homma-Takeda, Shino; Furusawa, Yoshiya; Wang, Jun; Konishi, Teruaki

    2017-10-01

    Understanding the mechanisms underlying the radiation-induced bystander effect (RIBE) and bi-directional signaling between irradiated carcinoma cells and their surrounding non-irradiated normal cells is relevant to cancer radiotherapy. The present study investigated propagation of RIBE signals between human lung carcinoma A549 cells and normal lung fibroblast WI38 cells in bystander cells, either directly or indirectly contacting irradiated A549 cells. We prepared A549-GFP/WI38 co-cultures and A549-GFP/A549 co-cultures, in which A549-GFP cells stably expressing H2BGFP were co-cultured with either A549 cells or WI38 cells, respectively. Using the SPICE-NIRS microbeam, only the A549-GFP cells were irradiated with 500 protons per cell. The level of γ-H2AX, a marker for DNA double-strand breaks (DSB), was subsequently measured for up to 24h post-irradiation in three categories of cells: (1) "targeted"/irradiated A549-GFP cells; (2) "neighboring"/non-irradiated cells directly contacting the "targeted" cells; and (3) "distant"/non-irradiated cells, which were not in direct contact with the "targeted" cells. We found that DSB repair in targeted A549-GFP cells was enhanced by co-cultured WI38 cells. The bystander response in A549-GFP/A549 cell co-cultures, as marked by γ-H2AX levels at 8h post-irradiation, showed a decrease to non-irradiated control level when approaching 24h, while the neighboring/distant bystander WI38 cells in A549-GFP/WI38 co-cultures was maintained at a similar level until 24h post-irradiation. Surprisingly, distant A549-GFP cells in A549-GFP/WI38 co-cultures showed time dependency similar to bystander WI38 cells, but not to distant cells in A549-GFP/A549 co-cultures. These observations indicate that γ-H2AX was induced in WI38 cells as a result of RIBE. WI38 cells were not only involved in rescue of targeted A549, but also in the modification of RIBE against distant A549-GFP cells. The present results demonstrate that radiation-induced bi

  4. Epidemiological features of lung giant cell carcinoma and therapy for patients with EGFR mutations based on case reports and the surveillance, epidemiology, and end results (SEER) database.

    PubMed

    Weng, Shan-Shan; Cao, Ying; Tang, Xiu-Jun; Zhu, Li-Zhen; Tan, Yi-Nuo; Dong, Cai-Xia; Chen, Jia-Qi; Shen, Hong; Yuan, Ying

    2017-04-11

    Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are the standard first line treatment for advanced non-small cell lung cancer (NSCLC) with sensitive EGFR mutations. Among NSCLC, giant cell carcinoma of the lung (GCCL) is a rare pathological subtype with poor prognosis, with no confirmed evidence about its epidemiological features or therapeutic efficiency of EGFR-TKIs. We present two advanced GCCLs with sensitive EGFR mutations, also collected the cases of GCCL from our hospital and the Surveillance, Epidemiology, and End Results (SEER) program. Kaplan-Meier methods and Cox proportional hazards modeling were used to perform the survival analyses. Both two cases of advanced GCCL with sensitive EGFR mutations benefited from EGFR-TKIs. Twelve GCCLs were recorded in our hospital from May 2006 to July 2015. GCCL is associated with males (83.3%) and smoking status (63.6%). The EGFR mutation rate was 40.0%. In SEER database, the total number of GCCLs was 184, 0.11% for all NSCLCs. In Kaplan-Meier analysis, the 5-year overall survival of GCCL patients was significantly lower than that of non-GCC NSCLC (16% and 19%; P<0.001), and it was confirmed in multivariate analysis. Further survival analyses indicated that male were more susceptible to GCCL and GCCL was prone to metastasize. Only age and M stage were independent prognostic factors for GCCL in the multivariate analysis. In conclusion, GCCL was an unfavorable prognostic factor and associated with males and metastasis. GCCL patients with sensitive EGFR mutations may also benefit from EGFR-TKI, we therefore recommend the evaluation of EGFR in the treatment of advanced GCCL.

  5. Assessing the Need for Adjuvant Chemotherapy After Stereotactic Body Radiation Therapy in Early-stage Non-small Cell Lung Carcinoma

    PubMed Central

    Bahig, Houda; Filion, Édith; Campeau, Marie-Pierre; Lambert, Louise; Roberge, David; Gorgos, Andrei-Bogdan; Vu, Toni

    2016-01-01

    Purpose Surgery remains the standard treatment for medically operable patients with early-stage non-small cell lung carcinoma (NSCLC). Following surgical resection, adjuvant chemotherapy is recommended for large tumors >4 cm. For unfit patients, stereotactic body radiation therapy (SBRT) has emerged as an excellent alternative to surgery. This study aims to assess patterns of recurrence and discuss the role of chemotherapy after SBRT for NSCLC. Methods We reviewed patients treated with SBRT for primary early-stage NSCLC between 2009 and 2015. Total target doses were between 50 and 60 Gy administered in three to eight fractions. All patients had a staging fluorodeoxyglucose (FDG) positron emission tomography (PET) integrated with computed tomography (CT) scan, and histologic confirmation was obtained whenever possible. Mediastinal staging was performed if lymph node involvement was suspected on CT or PET/CT. Survival outcomes were estimated using the Kaplan-Meier method. Results Among the 559 early-stage NSCLC patients treated with SBRT, 121 patients were stage T2N0. The one-year and three-year overall survival rates were 88% and 70%, respectively, for patients with T2 disease, compared to 95% and 81%, respectively, for the T1 patients (p<0.05). The one-year and three-year local control rates were equal in both groups (98% and 91%, respectively). In T2 patients, 25 (21%) presented a relapse, among which 21 (84%) were nodal or distant. The median survival of T2N0 patients following a relapse was 11 months. Conclusion Lung SBRT provides high local control rates, even for larger tumors. When patients relapse, the majority of them do so at regional or distant sites. These results raise the question as to whether adjuvant treatment should be considered following SBRT for larger tumors.  PMID:28070470

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

    PubMed

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

    2013-06-01

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

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

    PubMed

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

    2017-07-01

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

  8. Silencing stem cell factor attenuates stemness and inhibits migration of cancer stem cells derived from Lewis lung carcinoma cells.

    PubMed

    Wang, Li; Wang, JianTao; Li, Zhixi; Liu, YanYang; Jiang, Ming; Li, Yan; Cao, Dan; Zhao, Maoyuan; Wang, Feng; Luo, Feng

    2016-06-01

    Stem cell factor (SCF) plays an important role in tumor growth and metastasis. However, the function of SCF in regulating stemness and migration of cancer stem cells (CSCs) remains largely undefined. Here, we report that non-adhesive culture system can enrich and expand CSCs derived from Lewis lung carcinoma (LLC) cells and that the expression level of SCF in CSCs was higher than those in LLC cells. Silencing SCF via short hairpin (sh) RNA lentivirus transduction attenuated sphere formation and inhibited expressions of stemness genes, ALDH1, Sox2, and Oct4 of CSCs in vitro and in vivo. Moreover, SCF-silenced CSCs inhibited the migration and epithelial-mesenchymal transition, with decreased expression of N-cadherin, Vimentin, and increased expression of E-cadherin in vitro and in vivo. Finally, SCF-short hairpin RNA (shRNA) lentivirus transduction suppressed tumorigenicity of CSCs. Taken together, our findings unraveled an important role of SCF in CSCs derived from LLC cells. SCF might serve as a novel target for lung cancer therapy.

  9. E3 ubiquitin ligase Pirh2 enhances tumorigenic properties of human non-small cell lung carcinoma cells

    PubMed Central

    Fedorova, Olga; Shuvalov, Oleg; Merkulov, Valeriy; Vasileva, Elena; Antonov, Alexey; Barlev, Nikolai A.

    2016-01-01

    The product of RCHY1 human gene, Pirh2, is a RING-finger containing E3 ligase that modifies p53 with ubiquitin residues resulting in its subsequent degradation in proteasomes. Transcription of RCHY1 is regulated by p53 itself thus forming a negative regulatory feedback loop. Functionally, by eliminating p53, Pirh2 facilitates tumorigenesis. However, the role of Pirh2 in cancer cells lacking p53 is yet not well understood. Therefore, we decided to elucidate the role of Pirh2 in p53-negative human non-small cell lung carcinoma cells, H1299. We found that ectopic expression of Pirh2 enhanced cell proliferation, resistance to doxorubicin, and increased migration potential. Ablation of Pirh2 by specific shRNA reversed these phenotypes. Mechanistically, Pirh2 increased mRNA and protein levels of the c-Myc oncogene. The bioinformatics data indicate that co-expression of both c-Myc and Pirh2 strongly correlated with poor survival of lung cancer patients. Collectively, our results suggest that Pirh2 can be considered as a potential pharmacological target for developing anticancer therapies to treat p53-negative cancers. PMID:28191284

  10. Litchi seed extract inhibits epidermal growth factor receptor signaling and growth of Two Non-small cell lung carcinoma cells.

    PubMed

    Chung, Yuan-Chiang; Chen, Chin-Hui; Tsai, Yu-Ting; Lin, Chih-Cheng; Chou, Jyh-Ching; Kao, Ting-Yu; Huang, Chiu-Chen; Cheng, Chi-Hsuan; Hsu, Chih-Ping

    2017-01-05

    Litchi seeds possess rich amounts of phenolics and have been shown to inhibit proliferation of several types of cancer cells. However, the suppression of EGFR signaling in non-small cell lung cancer (NSCLC) by litchi seed extract (LCSE) has not been fully understood. In this study, the effects of LCSE on EGFR signaling, cell proliferation, the cell cycle and apoptosis in A549 adenocarcinoma cells and NCI- H661 large-cell carcinoma cells were examined. The results demonstrated that LCSE potently reduced the number of cancer cells and induced growth inhibition, cell-cycle arrest in the G1 or G2/M phase, and apoptotic death in the cellular experiment. Only low cytotoxicity effect was noted in normal lung MRC-5 cells. LCSE also suppressed cyclins and Bcl-2 and elevated Kip1/p27, Bax and caspase 8, 9 and 3 activities, which are closely associated with the downregulation of EGFR and its downstream Akt and Erk-1/-2 signaling. The results implied that LCSE suppressed EGFR signaling and inhibited NSCLC cell growth. This study provided in vitro evidence that LCSE could serve as a potential agent for the adjuvant treatment of NSCLC.

  11. Neurologic dysfunction in patients treated for small cell carcinoma of the lung: a clinical and radiological study

    SciTech Connect

    Chak, L.Y.; Zatz, L.M.; Wasserstein, P.; Cox, R.S.; Kushlan, P.D.; Porzig, K.J.; Sikic, B.I.

    1986-03-01

    The neurologic dysfunction in 7 patients treated for small cell carcinoma (SCC) of the lung by combination chemotherapy and prophylactic brain irradiation was evaluated. The disease appeared to be a diffuse encephalopathy frequently affecting the higher cortical functions. Five out of seven patients had progressive dysfunction leading to death in 1 to 26 months; one patient had stabilization of symptoms followed by death in 21 months, probably from the neurologic disease as well as SCC; one patient's symptoms improved. The clinical course of the neurologic disorder seemed different from the known reactions to brain irradiation and from the other neurologic syndromes associated with lung cancer. The relative contributions of cranial irradiation and treatment with chemotherapeutic agents in producing the neurotoxicity are not known. Computed tomographic (CT) brain scans done after the onset of symptoms did not show any focal signs or necrosis. However, there was a suggestion of progressive increase in intracranial fluid volume on the scans. The incidence of the disorder, 10.2% among a group of 49 patients, suggests the need for prospective studies to evaluate the problem.

  12. [Effect of DJ-1 siRNA on biological behavior of human lung squamous carcinoma SK-MES-1 cells].

    PubMed

    Wei, Wangli; Tang, Can'e; Zhan, Xianquan; Yi, Hong; Li, Cui

    2013-01-01

    RNA interference technology (siRNA) was used to inhibit the expression of DJ-1 gene in lung squamous cell carcinoma SK-MES-1 cells, and the cell biological behaviors were investigated to explore the function of DJ-1 gene. A targeted DJ-1 siRNA lentiviral vector with a green fluorescent protein (GFP) as a reporter was constructed. The constructed DJ-1 siRNA and control-siRNA vectors were infected into SK-MES-1 cells as experimental (DJ-1 siRNA) and control (Control siRNA) groups, respectively. The DJ-1 protein expression was determined by Western blot. The cell proliferation capability was measured with methyl thiazolyl tetrazolium (MTT). The cell cycle was analyzed by flow cytometry. The capability of cell migration was determined by Transwell method. Compared with control-siRNA and blank-control groups, the protein expression of DJ-1 gene was down-regulated, the capability of cell proliferation was obviously inhibited (P<0.01), the cell cycle was arrested with increased number of G1- and G2-phase cells and reduced number of S-phase cells, and the capability of cell migration was significantly decreased (P<0.01) in the DJ-1 siRNA-infected cells. DJ-1 gene might play a role in promoting cell proliferation and cell migration capability in vitro in lung cancer SK-MES-1 cells.

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

    PubMed Central

    Sundaram, Sneha; Yan, Lin

    2016-01-01

    The objective of this study was to determine whether a reduction in energy intake ameliorated the high-fat diet-enhanced spontaneous metastasis of Lewis lung carcinoma in mice. Male C57BL/6 mice were fed the AIN93G diet, a high-fat diet or a high-fat diet with a 5% restriction of the intake. Energy restriction reduced body adiposity and body weight, but maintained growth similar to mice fed the AIN93G diet. The high-fat diet significantly increased the number and size (cross-sectional area and volume) of metastases formed in lungs. Restricted feeding reduced the number of metastases by 23%, metastatic cross-sectional area by 32% and volume by 45% compared to the high-fat diet. The high-fat diet elevated plasma concentrations of proinflammatory cytokines (monocyte chemotactic protein-1, plasminogen activator inhibitor-1, leptin), angiogenic factors (vascular endothelial growth factor, tissue inhibitor of metalloproteinase-1) and insulin. Restricted feeding significantly reduced the high-fat diet-induced elevations in plasma concentrations of proinflammatory cytokines, angiogenic factors and insulin. These results demonstrated that a reduction in diet intake by 5% reduced high-fat diet-enhanced metastasis, which may be associated with the mitigation of adiposity and down-regulation of cancer-promoting proinflammatory cytokines and angiogenic factors. PMID:27582541

  14. Exome sequencing identifies frequent mutation of MLL2 in non–small cell lung carcinoma from Chinese patients

    PubMed Central

    Yin, Shanye; Yang, Jing; Lin, Bin; Deng, Wenjun; Zhang, Yuchao; Yi, Xianfu; Shi, Yufang; Tao, Yong; Cai, Jun; Wu, Chung-I; Zhao, Guoping; Hurst, Laurence D.; Zhang, Jie; Hu, Landian; Kong, Xiangyin

    2014-01-01

    Lung cancer is the most common cause of cancer mortality worldwide, with an estimated 1.4 million deaths each year. Here we report whole-exome sequencing of nine tumor/normal tissue pairs from Chinese patients with non-small cell lung carcinoma (NSCLC). This allows us to identify a number of significantly mutated genes in NSCLC, which were highly enriched in DNA damage repair, NF-κB pathway, JAK/STAT signaling and chromatin modification. Notably, we identify a histone-lysine methyltransferase gene, namely, MLL2, as one of the most significantly mutated genes in our screen. In a following validation study, we identify deleterious mutations of MLL2 in 12 out of 105 (11.4%) NSCLC patients. Additionally, reduced or lost expression of MLL2 was commonly observed in tumor tissues as compared with paired adjacent non-tumor tissues regardless of mutation status. Together, our study defines the landscape of somatic mutations in Chinese NSCLC and supports the role of MLL2 mutation in the pathogenesis of the disease. PMID:25112956

  15. ALDH7A1 expression is associated with recurrence in patients with surgically resected non-small-cell lung carcinoma

    PubMed Central

    Giacalone, Nicholas J; Den, Robert B; Eisenberg, Rosana; Chen, Heidi; Olson, Sandra J; Massion, Pierre P; Carbone, David P; Lu, Bo

    2013-01-01

    Aim The purpose of this study was to describe the prognostic significance of ALDH7A1 in surgically treated non-small-cell lung carcinoma. (NSCLC). Materials & methods We immunohistochemically analyzed ALDH7A1 expression in surgically resected NSCLC from 89 patients using a tissue microarray. Results ALDH7A1 staining was positive in 43 patients and negative in 44 patients, with two tumor sections missing. For stage I NSCLC patients, ALDH7A1 positivity was associated with decreased recurrence-free and overall survival. Multivariate analysis demonstrated that ALDH7Al-expressing NSCLC tumors had a significantly higher incidence of lung cancer recurrence compared with patients with ALDH7A1-negative tumors, although there was no association with overall survival. Conclusion For patients with NSCLC, low ALDH7A1 expression was associated with a decreased incidence of cancer recurrence. Specifically in stage I patients, negative staining for ALDH7A1 was associated with improved recurrence-free and overall survival, suggesting a predictive role in surgically treated patients. PMID:23647301

  16. Induction of apoptosis in human lung carcinoma A549 epithelial cells with an ethanol extract of Tremella mesenterica.

    PubMed

    Chen, Nan-Yin; Lai, Hsi-Huai; Hsu, Tai-Hao; Lin, Fang-Yi; Chen, Jian-Zhi; Lo, Hui-Chen

    2008-05-01

    Tremella mesenterica (TM) is a common food and folk medicine widely used in several Asian countries as a tonic for the lungs. In the present study, we compared the effects of extracellular polysaccharides (EPS), intracellular polysaccharides (IPS), and ethanol extract (EE) of Tremella mesenterica on the induction of apoptosis into human lung carcinoma A549 epithelial cells. The EE, but not the EPS or the IPS, almost completely inhibited the growth of A549 cells. The results of Annexin V-FITC/PI staining and flow cytometric analysis indicated that the percentage of Annexin V(+)/PI(-) cells in EE-treated cells increased to 32.8%. The results of further investigation showed a disruption of mitochondrial transmembrane potential (DeltaPsi(m)), the production of reactive oxygen species (ROS), and the activation of caspase-3 protein in EE-treated cells. These findings suggest that EE can decrease cell viability and induce apoptosis in A549 cell lines by activating a mitochondrial pathway.

  17. 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

  18. TUMORAL TISSUE SPECIFIC PROMOTER HYPERMETHYLATION OF DISTINCT TUMOR SUPPRESSOR GENES IN A CASE WITH NONSMALL CELL LUNG CARCINOMA: A CASE REPORT

    PubMed Central

    Arslan, Sulhattin; Dogan, Tamer; Koksal, Binnur; Yildirim, Malik Ejder; Gumus, Cesur; Elagoz, Sahenda; Akkurt, Ibrahim; Ozdemir, Oztürk

    2008-01-01

    SUMMARY Objective: Non-small cell lung carcinoma is an aggressive phenomenon and the epigenetical alterations of some tumor supressor genes have been reported for the different tumor types. Case Presentation: It is presented a case report concerning a 43 years old male with NSCLC on the lower segment of the right lung. The patient underwent a diag-nostic excisional thin-needle biopsy and after the histological confirmation. We examined the promoter methylation status of some distinct tumor supressor genes in tumoral and blood tissues of the case after sodium bisulfite conversion and DNA amplification with methylation specific multiplex PCR technique. Both tissues were also searched for G to A transitions in codons 12 and 13 of the K-ras proto-oncogene. Results: Tumor specimen showed fully methyl pattern profiles for the SFRP2, p16, DAPK1 and partially hyper-methylated profile for the p53 and MGMT genes in this case with non-small lung carci-noma. Blood speicemen showed normal hypomethylated profiles for all studied TS genes. The K-ras proto-oncogene was in normal structure both in blood and tumoral spiecemens that examined. Conclusion: Results indicate that genes exhibit tumor suppressor activi-ties in blood, but exhibit epigenetic inactivation in carcinoma cell. These findings strongly support the hypothesis that epigenetic mechanisms may play an important role in the non-small cell lung carcinogenesis in human. PMID:21264081

  19. Large cell carcinoma of the lung: clinically oriented classification integrating immunohistochemistry and molecular biology.

    PubMed

    Rossi, G; Mengoli, M C; Cavazza, A; Nicoli, D; Barbareschi, M; Cantaloni, C; Papotti, M; Tironi, A; Graziano, P; Paci, M; Stefani, A; Migaldi, M; Sartori, G; Pelosi, G

    2014-01-01

    This study aimed at challenging pulmonary large cell carcinoma (LLC) as tumor entity and defining different subgroups according to immunohistochemical and molecular features. Expression of markers specific for glandular (TTF-1, napsin A, cytokeratin 7), squamous cell (p40, p63, cytokeratins 5/6, desmocollin-3), and neuroendocrine (chromogranin, synaptophysin, CD56) differentiation was studied in 121 LCC across their entire histological spectrum also using direct sequencing for epidermal growth factor receptor (EGFR) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations and FISH analysis for ALK gene translocation. Survival was not investigated. All 47 large cell neuroendocrine carcinomas demonstrated a true neuroendocrine cell lineage, whereas all 24 basaloid and both 2 lymphoepithelioma-like carcinomas showed squamous cell markers. Eighteen out of 22 clear cell carcinomas had glandular differentiation, with KRAS mutations being present in 39 % of cases, whereas squamous cell differentiation was present in four cases. Eighteen out of 20 large cell carcinomas, not otherwise specified, had glandular differentiation upon immunohistochemistry, with an exon 21 L858R EGFR mutation in one (5 %) tumor, an exon 2 KRAS mutation in eight (40 %) tumors, and an ALK translocation in one (5 %) tumor, whereas two tumors positive for CK7 and CK5/6 and negative for all other markers were considered adenocarcinoma. All six LCC of rhabdoid type expressed TTF-1 and/or CK7, three of which also harbored KRAS mutations. When positive and negative immunohistochemical staining for these markers was combined, three subsets of LCC emerged exhibiting glandular, squamous, and neuroendocrine differentiation. Molecular alterations were restricted to tumors classified as adenocarcinoma. Stratifying LCC into specific categories using immunohistochemistry and molecular analysis may significantly impact on the choice of therapy.

  20. 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.

  1. [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

  2. [Nimotuzumab Combined with Chemotherapy as Second- or Later-line 
in the Treatment of Advanced Lung Squamous Cell Carcinoma].

    PubMed

    Luo, Yang; Li, Junling; Wang, Yan; Hao, Xuezhi; Qu, Fenglian

    2016-10-20

    Epidermal growth factor receptor (EGFR) is commonly overexpressed in lung squamous cell carcinoma and has been associated with impaired prognosis. The aim of this study was to observe the efficacy and safety of nimotuzumab, a anti-EGFR monoclonal antibody, combined with chemotherapy as second- or later-line in the treatment of advanced lung squamous cell carcinoma. A retrospective analysis of clinical data was conducted in 13 patients with advanced lung squamous cell carcinoma, who were administered with nimotuzumab combined with chemotherapy as second-line or later-line treatment. The efficacy of therapy was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and safety by National Cancer Institute Common Toxicity Criteria (NCI-CTC) 4.0. Of the 13 advanced squamous-cell lung cancer patients, one patient had complete response (CR), 2 patients had partial response (PR), 4 cases had stable disease (SD), and 6 patients had progressive disease. The overall response rate (ORR) was 23.1% and clinical benefit rate (CBR) was 53.8%. EGFR expression were detected by immunohistochemistry in 6 patients and the results showed 5 patients were EGFR 3+ and the other was EGFR 2+. Of these 6 EGFR positive patients, 1 case had CR, 1 case had PR and 4 cases had SD; ORR was 33.3% and CBR was 100.0%. Grade 3/4 hematological toxicities were observed in 3 (23.1%) patients, and non-hametological toxicities were mild. Nimotuzumab-associated skin rash was found in 2 (15.4%) patients. Nimotuzumab combined with chemotherapy as second- or later-line therapy for advanced squamous cell lung carcinoma was active and well-tolerated, especially for those patients with EGFR positive.

  3. Prognostic Impact of Immune Microenvironment in Lung Squamous Cell Carcinoma: Tumor-Infiltrating CD10+ Neutrophil/CD20+ Lymphocyte Ratio as an Independent Prognostic Factor

    PubMed Central

    Kadota, Kyuichi; Nitadori, Jun-ichi; Ujiie, Hideki; Buitrago, Daniel H.; Woo, Kaitlin M.; Sima, Camelia S.; Travis, William D.; Jones, David R.; Adusumilli, Prasad S.

    2015-01-01

    Introduction We previously reported the prognostic significance of the lung adenocarcinoma immune microenvironment. In this study, we preformed comprehensive analysis of immune markers and their associations with prognosis in patients with lung squamous cell carcinoma. Methods We reviewed surgically resected, solitary lung squamous cell carcinoma patients (n = 485; 1999 to 2009) that were randomly split into a training cohort (n = 331) and validation cohort (n = 154). We constructed tissue microarrays and performed immunostaining for CD3, CD45RO, CD8, CD4, FoxP3, CD20, CD68, CXCL12, CXCR4, CCR7, IL-7R, and IL-12Rβ2. Overall survival (OS) was analyzed using the log-rank test and the Cox proportional hazards model. Results Analysis of single immune cell infiltration revealed that high tumor-infiltrating CD10+ neutrophils were associated with worse prognoses in the training cohort (P = 0.021). Analysis of biologically relevant immune cell combinations identified that patients with high CD10+ neutrophil and low CD20+ lymphocyte had a significantly worse OS (5-year OS, 42%) than those with other combinations of CD10 and CD20 (5-year OS, 62%; P < 0.001); this was confirmed in the validation cohort (P = 0.032). For the multivariate analysis, high CD10/low CD20 immune cell infiltration was an independent predictor of OS in both the training cohort (HR = 1.61, P = 0.006) and validation cohort (HR = 1.75; P = 0.043). Conclusions High CD10+/low CD20+ immune cell infiltration ratio is a significant prognostic factor of lung squamous cell carcinoma. Immunomodulatory therapy of tumor-specific neutrophil and B lymphocyte responses may have applicability in the treatment of lung squamous cell carcinoma. PMID:26291010

  4. Bronchioloalveolar carcinoma and lung adenocarcinoma: the clinical importance and research relevance of the 2004 World Health Organization pathologic criteria.

    PubMed

    Travis, William D; Garg, Kavita; Franklin, Wilbur A; Wistuba, Ignacio I; Sabloff, Bradley; Noguchi, Masayuki; Kakinuma, Ryutaro; Zakowski, Maureen; Ginsberg, Michelle; Padera, Robert; Jacobson, Francine; Johnson, Bruce E; Hirsch, Fred; Brambilla, Elizabeth; Flieder, Douglas B; Geisinger, Kim R; Thunnissen, Frederik; Kerr, Keith; Yankelevitz, David; Franks, Teri J; Galvin, Jeffrey R; Henderson, Douglas W; Nicholson, Andrew G; Hasleton, Philip S; Roggli, Victor; Tsao, Ming-Sound; Cappuzzo, Federico; Vazquez, Madeline

    2006-11-01

    Advances in the pathology and computed tomography (CT) of lung adenocarcinoma and bronchioloalveolar carcinoma (BAC) have demonstrated important new prognostic features that have led to changes in classification and diagnostic criteria. The literature and a set of cases were reviewed by a pathology/CT review panel of pathologists and radiologists who met during a November 2004 International Association for the Study of Lung Cancer/American Society of Clinical Oncology consensus workshop in New York. The group addressed the question of whether sufficient data exist to modify the 2004 World Health Organization (WHO) classification of adenocarcinoma and BAC to define a "minimally invasive" adenocarcinoma with BAC. The problems of diffuse and/or multicentric BAC and adenocarcinoma were evaluated. The clinical concept of BAC needs to be reevaluated with careful attention to the new 2004 WHO criteria because of the major clinical implications. Existing data indicate that patients with solitary, small, peripheral BAC have a 100% 5-year survival rate. The favorable prognostic impact of the restrictive criteria for BAC is already being detected in major epidemiologic data sets such as the Surveillance Epidemiology and End-Results registry. Most lung adenocarcinomas, including those with a BAC component, are invasive and consist of a mixture of histologic patterns. Therefore, they are best classified as adenocarcinoma, mixed subtype. This applies not only to adenocarcinomas with a solitary nodule presentation but also to tumors with a diffuse/multinodular pattern. The percentage of BAC versus invasive components in lung adenocarcinomas seems to be prognostically important. However, at the present time, a consensus definition of "minimally invasive" BAC with a favorable prognosis was not recommended by the panel, so the 1999/2004 WHO criteria for BAC remain unchanged. In small biopsy specimens or cytology specimens, recognition of a BAC component is possible. However, it is

  5. Theabrownin Inhibits Cell Cycle Progression and Tumor Growth of Lung Carcinoma through c-myc-Related Mechanism

    PubMed Central

    Zhou, Li; Wu, Feifei; Jin, Wangdong; Yan, Bo; Chen, Xin; He, Yingfei; Yang, Weiji; Du, Wenlin; Zhang, Qiang; Guo, Yonghua; Yuan, Qiang; Dong, Xiaoqiao; Yu, Wenhua; Zhang, Jin; Xiao, Luwei; Tong, Peijian; Shan, Letian; Efferth, Thomas

    2017-01-01

    Green tea, the fresh leaves of Camellia sinensis, is not only a health-promoting beverage but also a traditional Chinese medicine used for prevention or treatment of cancer, such as lung cancer. Theabrownin (TB) is the main fraction responsible for the medicinal effects of green tea, but whether it possesses anti-cancer effect is unknown yet. This study aimed to determine the in vitro and in vivo anti-lung cancer effect of TB and explore the underlying molecular mechanism, by using A549 cell line and Lewis lung carcinoma-bearing mice. In cellular experiment, MTT assay was performed to evaluate the inhibitory effect and IC50 values of TB, and flow cytometry was conducted to analyze the cell cycle progression affected by TB. In animal experiment, mice body mass, tumor incidence, tumor size and tumor weight were measured, and histopathological analysis on tumor was performed with Transferase dUTP nick-end labeling staining. Real time PCR and western blot assays were adopted to detect the expression of C-MYC associated genes and proteins for mechanism clarification. TB was found to inhibit A549 cell viability in a dose- and time-dependent manner and block A549 cell cycle at G0/G1 phase. Down-regulation of c-myc, cyclin A, cyclin D, cdk2, cdk4, proliferation of cell nuclear antigen and up-regulation of p21, p27, and phosphate and tension homolog in both gene and protein levels were observed with TB treatment. A c-myc-related mechanism was thereby proposed, since c-myc could transcriptionally regulate all other genes in its downstream region for G1/S transitions of cell cycle and proliferation of cancer cells. This is the first report regarding the anti-NSCLC effect and the underlying mechanism of TB on cell cycle progression and proliferation of A549 cells. The in vivo data verified the in vitro result that TB could significantly inhibit the lung cancer growth in mice and induce apoptosis on tumors in a dose-dependent manner. It provides a promising candidate of natural

  6. An intracapsular carcinoma ex pleomorphic adenoma with lung metastases composed exclusively of benign elements: histological evidence of a continuum between metastasizing pleomorphic adenoma and carcinoma ex pleomorphic adenoma.

    PubMed

    Weissferdt, Annikka; Langman, Gerald

    2010-07-15

    Malignant mixed tumors of the salivary glands, encompassing carcinoma ex pleomorphic adenoma (ca ex PA), carcinosarcoma and metastasizing pleomorphic adenoma (mPA), are rare neoplasms. Ca ex PA arises in a pre-existing pleomorphic adenoma (PA). When the malignant component does not breach the capsule of the parent PA, the lesion is termed intracapsular ca ex PA, a neoplasm which is thought to have no metastatic potential. Metastatic deposits of ca ex PA are composed exclusively of malignant elements or mixed benign and malignant components. We describe the case of a 62-year-old female with an intracapsular ca ex PA of the buccal mucosa with subsequent metastases to the lung. The metastatic deposits resembled benign PA with no histological evidence of malignancy. This pattern of spread is described with mPA, an entity that caused controversy in the past regarding its exact classification as a benign or malignant tumor. The possibility that ca ex PA originates from a mPA, with intracapsular ca ex PA representing an intermediate lesion in a histological continuum, is discussed.

  7. 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

    2015-06-11

    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.

  8. Pomegranate fruit extract inhibits prosurvival pathways in human A549 lung carcinoma cells and tumor growth in athymic nude mice.

    PubMed

    Khan, Naghma; Hadi, Naghma; Afaq, Farrukh; Syed, Deeba N; Kweon, Mee-Hyang; Mukhtar, Hasan

    2007-01-01

    Developing novel mechanism-based chemopreventive approaches for lung cancer through the use of dietary substances which humans can accept has become an important goal. In the present study, employing normal human bronchial epithelial cells (NHBE) and human lung carcinoma A549 cells, we first compared the growth inhibitory effects of pomegranate fruit extract (PFE). Treatment of PFE (50-150 microg/ml) for 72 h was found to result in a decrease in the viability of A549 cells but had only minimal effects on NHBE cells as assessed by the MTT and Trypan blue assays. PFE treatment of A549 cells also resulted in dose-dependent arrest of cells in G0-G1 phase of the cell cycle (as assessed by DNA cell cycle analysis). We further found that PFE treatment also resulted in (i) induction of WAF1/p21 and KIP1/p27, (ii) decrease in the protein expressions of cyclins D1, D2 and E, and (iii) decrease in cyclin-dependent kinase (cdk) 2, cdk4 and cdk6 expression. The treatment of cells with PFE inhibited (i) phosphorylation of MAPK proteins, (ii) inhibition of PI3K, (iii) phosphorylation of Akt at Thr308, (iv) NF-kappaB and IKKalpha, (v) degradation and phosphorylation of IkappaBalpha, and (vi) Ki-67 and PCNA. We also found that PFE treatment to A549 cells resulted in inhibition of NF-kappaB DNA-binding activity. Oral administration of PFE (0.1 and 0.2%, wt/vol) to athymic nude mice implanted with A549 cells resulted in a significant inhibition in tumor growth. Our results provide a suggestion that PFE can be a useful chemopreventive/chemotherapeutic agent against human lung cancer.

  9. Prognostic significance of PIK3CA and SOX2 in Asian patients with lung squamous cell carcinoma.

    PubMed

    Iijima, Yoshihito; Seike, Masahiro; Noro, Rintaro; Ibi, Takayuki; Takeuchi, Shingo; Mikami, Iwao; Koizumi, Kiyoshi; Usuda, Jitsuo; Gemma, Akihiko

    2015-02-01

    The recent development of human genome studies has demonstrated the possibility of alteration of several genes as oncogenic driver mutations of lung squamous cell carcinoma (SQCC). FGFR1, PIK3CA and SOX2 genes have been recognized as candidate driver genes of SQCC. The aim of the present study was to evaluate FGFR1, PIK3CA and SOX2 protein expression in SQCC and determine whether the expression of these can be used as prognostic biomarkers. We evaluated the relationships between FGFR1, PIK3CA and SOX2 expression by immunohistochemical analysis and overall survival in lung SQCC patients with stage I-III that originated from China, United States and Japan. FGFR1-positive, PIK3CA-negative and SOX2-positive staining each showed trends toward better survival, although the differences were not statistically significant in a Chinese cohort of 57 patients. Patients with PIK3CA-negative and SOX2-positive staining (PIK3CA(-)/SOX2(+)) showed better prognosis compared with those with PIK3CA-positive or SOX2-negative staining in the Chinese cohort (p=0.04). The robustness of PIK3CA(-)/SOX2(+) classification as having prognostic significance was validated in an independent set of 66 Japanese cohort patients (p=0.007). Japanese SQCC patients with stage I were evaluated separately and PIK3CA(-)/SOX2(+) cases had significantly better survival than the group with PIK3CA-positive or SOX2-negative status (p=0.03). In univariate and multivariable Cox proportional hazards models of Asian stage I patients, the PIK3CA(-)/SOX2(+) classification was statistically significantly associated with survival and was an independent prognostic factor. Classification by PIK3CA and SOX2 protein expression is useful for predicting the prognosis of Asian patients with lung SQCC with stage I.

  10. EGFR mutation in squamous cell carcinoma of the lung: does it carry the same connotation as in adenocarcinomas?

    PubMed

    Joshi, Amit; Zanwar, Saurabh; Noronha, Vanita; Patil, Vijay M; Chougule, Anuradha; Kumar, Rajiv; Janu, Amit; Mahajan, Abhishek; Kapoor, Akhil; Prabhash, Kumar

    2017-01-01

    EGFR tyrosine kinase inhibitors (TKIs) have greatly improved the outcomes of EGFR mutation-positive adenocarcinomas of the lung. In contrast, the significance of EGFR mutation in metastatic squamous cell carcinoma (SCC) of the lung has been debated. All patients with metastatic SCC who underwent EGFR mutation testing at our center from 2010 to 2015 were included for analysis. EGFR kinase domain mutations were tested using Taqman-based real-time polymerase chain reaction (PCR). Response assessment was done using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1. Kaplan-Meier method was used for calculating progression-free survival (PFS) and overall survival (OS). EGFR mutation was detected in 29 out of 639 patients with SCC. Furthermore, 19 out of the 29 patients received TKIs at some point during their treatment. TKI therapy led to a partial response in 5 out of 19 patients and stable disease in 4 out of 19 patients. The median PFS of patients treated with TKIs was 5.0 months. The median OS of the whole EGFR-positive SCC cohort was 6.6 months. On univariate analysis, patients having received TKI therapy was the only factor associated with a significantly better OS of 13.48 months versus 2.58 months (P=0.000). On multivariate analysis, patients receiving TKI therapy, Eastern Cooperative Oncology Group-Performance Scale (ECOG-PS) score <2, EGFR exon 19 mutation and nonsmoking status were associated with significantly better OS. EGFR mutation in SCC of the lung predicts a better outcome if the patient is given TKI, but it may be inferior to the outcomes seen in EGFR-positive adenocarcinomas treated with TKI.

  11. Targeting CXCR4 and FAK reverses doxorubicin resistance and suppresses invasion in non-small cell lung carcinoma.

    PubMed

    Dragoj, Miodrag; Milosevic, Zorica; Bankovic, Jasna; Tanic, Nikola; Pesic, Milica; Stankovic, Tijana

    2017-02-01

    Current high lung cancer mortality rates are mainly due to the occurrence of metastases and therapeutic resistance. Therefore, simultaneous targeting of these processes may be a valid approach for the treatment of this type of cancer. Here, we assessed relationships between CXC chemokine receptor type 4 (CXCR4) and focal adhesion kinase (FAK) gene expression levels and expression levels of the drug resistance-related genes ABCB1 and ABCC1, and tested the potential of CXCR4 and FAK inhibitors to reverse doxorubicin (DOX) resistance and to decrease the invasive capacity of non-small cell lung carcinoma (NSCLC) cells. qRT-PCR was used for gene expression analyses in primary lung tissue samples obtained from 30 NSCLC patients and the human NSCLC-derived cell lines NCI-H460, NCI-H460/R and COR-L23. MTT, flow cytometry, cell death and β-galactosidase activity assays were used to assess the in vitro impact of CXCR4 and FAK inhibitors on DOX sensitivity. In addition, invasion and gelatin degradation assays were used to assess the in vitro impact of the respective inhibitors on metastasis-related processes in combination with DOX treatment. We found that ABCB1 over-expression was significantly associated with CXCR4 and FAK over-expression, whereas ABCC1 over-expression was associated with increased FAK expression. We also found that CXCR4 and FAK inhibitors strongly synergized with DOX in reducing cell viability, arresting the cell cycle in the S or G2/M phases and inducing senescence. Additionally, we found that DOX enhanced the anti-invasive potential of CXCR4 and FAK inhibitors by reducing gelatin degradation and invasion. From our data we conclude that targeting of CXCR4 and FAK may overcome ABCB1 and ABCC1-dependent DOX resistance in NSCLC cells and that simultaneous treatment of these cells with DOX may potentiate the anti-invasive effects of CXCR4 and FAK inhibitors.

  12. Vitamin D Repletion Reduces the Progression of Premalignant Squamous Lesions in the NTCU Lung Squamous Cell Carcinoma Mouse Model

    PubMed Central

    Mazzilli, Sarah A.; Hershberger, Pamela A.; Reid, Mary E.; Bogner, Paul N.; Atwood, Kristopher; Trump, Donald L.; Johnson, Candace S.

    2015-01-01

    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 2000 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 % of the surface of large airways containing high-grade dysplastic (HGD) lesions were vitamin D-deficient +NTCU (DN), 22.7 % (p<0.05 compared to 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 to SN mice, DN mice exhibited a 3-fold increase (p <0.005) in circulating white blood cells (WBC), a 20% (p <0.05) increase in IL-6 levels, and a 4 -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

  13. 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.

  14. EGFR mutation in squamous cell carcinoma of the lung: does it carry the same connotation as in adenocarcinomas?

    PubMed Central

    Joshi, Amit; Zanwar, Saurabh; Noronha, Vanita; Patil, Vijay M; Chougule, Anuradha; Kumar, Rajiv; Janu, Amit; Mahajan, Abhishek; Kapoor, Akhil; Prabhash, Kumar

    2017-01-01

    Background EGFR tyrosine kinase inhibitors (TKIs) have greatly improved the outcomes of EGFR mutation-positive adenocarcinomas of the lung. In contrast, the significance of EGFR mutation in metastatic squamous cell carcinoma (SCC) of the lung has been debated. Methods All patients with metastatic SCC who underwent EGFR mutation testing at our center from 2010 to 2015 were included for analysis. EGFR kinase domain mutations were tested using Taqman-based real-time polymerase chain reaction (PCR). Response assessment was done using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1. Kaplan–Meier method was used for calculating progression-free survival (PFS) and overall survival (OS). Results EGFR mutation was detected in 29 out of 639 patients with SCC. Furthermore, 19 out of the 29 patients received TKIs at some point during their treatment. TKI therapy led to a partial response in 5 out of 19 patients and stable disease in 4 out of 19 patients. The median PFS of patients treated with TKIs was 5.0 months. The median OS of the whole EGFR-positive SCC cohort was 6.6 months. On univariate analysis, patients having received TKI therapy was the only factor associated with a significantly better OS of 13.48 months versus 2.58 months (P=0.000). On multivariate analysis, patients receiving TKI therapy, Eastern Cooperative Oncology Group–Performance Scale (ECOG-PS) score <2, EGFR exon 19 mutation and nonsmoking status were associated with significantly better OS. Conclusion EGFR mutation in SCC of the lung predicts a better outcome if the patient is given TKI, but it may be inferior to the outcomes seen in EGFR-positive adenocarcinomas treated with TKI. PMID:28405166

  15. [Afatinib in patients with squamous cell carcinoma of the lung: current context and the option of oral treatment].

    PubMed

    Cobo, Manuel; Gutiérrez, Vanesa; Rodelo, Luis; López, Omar; Ruiz, María; Godoy, Ana

    2016-04-01

    Squamous cell carcinoma (SCC) of the lung represents 30% of non-small cell lung cancers (NSCLC). Docetaxel and the EGFR tyrosine kinase inhibitor (TKI), erlotinib, are the only two drugs approved for second-line treatment of advanced SCC. The sensitivity of SCC to TKIs can be explained by EGFR overexpression. Erlotinib demonstrated a significant benefit in terms of overall survival (OS) in successive lines in NSCLC, including squamous histology. The magnitude of this benefit is similar to that of chemotherapy. Afatinib is an irreversible inhibitor of the entire ErbB family (EGFR, HER2-4) that has recently been approved for its current indication, advanced EGFR mutation-positive NSCLC and has well-defined and manageable toxicity, mainly gastrointestinal and cutaneous. The LUX-Lung 8 study was a phase III randomized trial in patients with NSCLC with squamous histology that compared erlotinib versus afatinib as second-line treatment. A total of 795 patients were included and a significant benefit was observed for afatinib in progression-free survival (2.7 vs 1.9 months (HR 0.79 [95%CI 0.68-0.91]; p=0.0012) and in OS (7.9 vs 6.8 months (HR 0.81 [95%CI 0.69-0.95]; p=0.0077), as well as a significant improvement in OS at 12 and 18 months. More diarrhoea and stomatitis was observed with afatinib and more rash with erlotinib, but the overall proportion of toxicity was similar in each group. Afatinib offered better results in quality of life. In summary, afatinib is a second-line treatment option in squamous NSCLC based on its survival advantage over erlotinib.

  16. Computerized lung nodule detection: comparison of performance for low-dose and standard-dose helical CT scans

    NASA Astrophysics Data System (ADS)

    Armato, Samuel G., III; Giger, Maryellen L.; Doi, Kunio; Bick, Ulrich; MacMahon, Heber

    2001-07-01

    The vast amount of image data acquired during a computed tomography (CT) scan makes lung nodule detection a burdensome task. Moreover, the growing acceptance of low-dose CT for lung cancer screening promises to further impact radiologists' workloads. Therefore, we have developed a computerized method to automatically analyze structures within a CT scan and identify those structures that represent lung nodules. Gray-level thresholding is performed to segment the lungs in each section to produce a segmented lung volume, which is then iteratively thresholded. At each iteration, remaining voxels are grouped into contiguous three-dimensional structures. Structures that satisfy a volume criterion then become nodule candidates. The set of nodule candidates is subjected to feature analysis. To distinguish candidates representing nodule and non-nodule structures, a rule-based approach is combined with an automated classifier. This method was applied to 43 standard-dose (diagnostic) CT scans and 13 low-dose CT scans. The method achieved an overall detection sensitivity of 71% with 1.5 false-positive detections per section on the standard-dose database and 71% sensitivity with 1.2 false-positive detections per section on the low-dose database. This automated method demonstrates promising performance in its ability to accurately detect lung nodules in standard-dose and low-dose CT images.

  17. Weighted gene co-expression network analysis in identification of metastasis-related genes of lung squamous cell carcinoma based on the Cancer Genome Atlas database.

    PubMed

    Tian, Feng; Zhao, Jinlong; Fan, Xinlei; Kang, Zhenxing

    2017-01-01

    Lung squamous cell carcinoma (lung SCC) is a common type of malignancy. Its pathogenesis mechanism of tumor development is unclear. The aim of this study was to identify key genes for diagnosis biomarkers in lung SCC metastasis. We searched and downloaded mRNA expression data and clinical data from The Cancer Genome Atlas (TCGA) database to identify differences in mRNA expression of primary tumor tissues from lung SCC with and without metastasis. Gene co-expression network analysis, protein-protein interaction (PPI) network, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and quantitative real-time polymerase chain reactions (qRT-PCR) were used to explore the biological functions of the identified dysregulated genes. Four hundred and eighty-two differentially expressed genes (DEGs) were identified between lung SCC with and without metastasis. Nineteen modules were identified in lung SCC through weighted gene co-expression network analysis (WGCNA). Twenty-three DEGs and 26 DEGs were significantly enriched in the respective pink and black module. KEGG pathway analysis displayed that 26 DEGs in the black module were significantly enriched in bile secretion pathway. Forty-nine DEGs in the two gene co-expression module were used to construct PPI network. CFTR in the black module was the hub protein, had the connectivity with 182 genes. The results of qRT-PCR displayed that FIGF, SFTPD, DYNLRB2 were significantly down-regulated in the tumor samples of lung SCC with metastasis and CFTR, SCGB3A2, SSTR1, SCTR, ROPN1L had the down-regulation tendency in lung SCC with metastasis compared to lung SCC without metastasis. The dysregulated genes including CFTR, SCTR and FIGF might be involved in the pathology of lung SCC metastasis and could be used as potential diagnosis biomarkers or therapeutic targets for lung SCC.

  18. Genome-Wide Association Study Identifies a Novel Susceptibility Locus at 12q23.1 for Lung Squamous Cell Carcinoma in Han Chinese

    PubMed Central

    Wu, Chen; Guo, Huan; Zhou, Baosen; Lv, Jiachun; Lu, Daru; Shi, Yongyong; Shu, Yongqian; Xu, Lin; Chu, Minjie; Wang, Cheng; Zhang, Ruyang; Dai, Juncheng; Jiang, Yue; Yu, Dianke; Ma, Hongxia; Zhao, Xueying; Yin, Zhihua; Yang, Lei; Li, Zhiqiang; Deng, Qifei; Cao, Songyu; Qin, Zhenzhen; Gong, Jianhang; Sun, Chongqi; Wang, Jiucun; Wu, Wei; Zhou, Guoquan; Chen, Hongyan; Guan, Peng; Chen, Yijiang; Liu, Xiangyang; Liu, Li; Xu, Pin; Han, Baohui; Bai, Chunxue; Zhao, Yuxia; Zhang, Haibo; Yan, Ying; Liu, Jibin; Amos, Christopher I.; Chen, Feng; Tan, Wen; Jin, Li; Wu, Tangchun; Hu, Zhibin; Lin, Dongxin; Shen, Hongbing

    2013-01-01

    Adenocarcinoma (AC) and squamous cell carcinoma (SqCC) are two major histological subtypes of lung cancer. Genome-wide association studies (GWAS) have made considerable advances in the understanding of lung cancer susceptibility. Obvious heterogeneity has been observed between different histological subtypes of lung cancer, but genetic determinants in specific to lung SqCC have not been systematically investigated. Here, we performed the GWAS analysis specifically for lung SqCC in 833 SqCC cases and 3,094 controls followed by a two-stage replication in additional 2,223 lung SqCC cases and 6,409 controls from Chinese populations. We found that rs12296850 in SLC17A8-NR1H4 gene region at12q23.1 was significantly associated with risk of lung SqCC at genome-wide significance level [additive model: odds ratio (OR) = 0.78, 95% confidence interval (CI) = 0.72–0.84, P = 1.19×10−10]. Subjects carrying AG or GG genotype had a 26% (OR = 0.74, 95% CI = 0.67–0.81) or 32% (OR = 0.68, 95% CI = 0.56–0.83) decreased risk of lung SqCC, respectively, as compared with AA genotype. However, we did not observe significant association between rs12296850 and risk of lung AC in a total of 4,368 cases with lung AC and 9,486 controls (OR = 0.96, 95% CI = 0.90–1.02, P = 0.173). These results indicate that genetic variations on chromosome 12q23.1 may specifically contribute to lung SqCC susceptibility in Chinese population. PMID:23341777

  19. Weighted gene co-expression network analysis in identification of metastasis-related genes of lung squamous cell carcinoma based on the Cancer Genome Atlas database

    PubMed Central

    Tian, Feng; Zhao, Jinlong; Kang, Zhenxing

    2017-01-01

    Background Lung squamous cell carcinoma (lung SCC) is a common type of malignancy. Its pathogenesis mechanism of tumor development is unclear. The aim of this study was to identify key genes for diagnosis biomarkers in lung SCC metastasis. Methods We searched and downloaded mRNA expression data and clinical data from The Cancer Genome Atlas (TCGA) database to identify differences in mRNA expression of primary tumor tissues from lung SCC with and without metastasis. Gene co-expression network analysis, protein-protein interaction (PPI) network, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and quantitative real-time polymerase chain reactions (qRT-PCR) were used to explore the biological functions of the identified dysregulated genes. Results Four hundred and eighty-two differentially expressed genes (DEGs) were identified between lung SCC with and without metastasis. Nineteen modules were identified in lung SCC through weighted gene co-expression network analysis (WGCNA). Twenty-three DEGs and 26 DEGs were significantly enriched in the respective pink and black module. KEGG pathway analysis displayed that 26 DEGs in the black module were significantly enriched in bile secretion pathway. Forty-nine DEGs in the two gene co-expression module were used to construct PPI network. CFTR in the black module was the hub protein, had the connectivity with 182 genes. The results of qRT-PCR displayed that FIGF, SFTPD, DYNLRB2 were significantly down-regulated in the tumor samples of lung SCC with metastasis and CFTR, SCGB3A2, SSTR1, SCTR, ROPN1L had the down-regulation tendency in lung SCC with metastasis compared to lung SCC without metastasis. Conclusions The dysregulated genes including CFTR, SCTR and FIGF might be involved in the pathology of lung SCC metastasis and could be used as potential diagnosis biomarkers or therapeutic targets for lung SCC. PMID:28203405

  20. Peroxisome proliferator-activated receptor-gamma ligands suppress fibronectin gene expression in human lung carcinoma cells: involvement of both CRE and Sp1.

    PubMed

    Han, Shouwei; Ritzenthaler, Jeffrey D; Rivera, Hilda N; Roman, Jesse

    2005-09-01

    Lung carcinoma often occurs in patients with chronic lung disease such as tobacco-related emphysema and asbestos-related pulmonary fibrosis. These diseases are characterized by dramatic alterations in the content and composition of the lung extracellular matrix, and we believe this "altered" matrix has the ability to promote lung carcinoma cell growth. One extracellular matrix molecule shown to be altered in these lung diseases is fibronectin (Fn). We previously reported increased growth and survival of non-small cell lung carcinoma (NSCLC) cells exposed to Fn. Thus Fn may serve as a mitogen/survival factor for NSCLC and therefore represents a novel target for anti-cancer strategies. To this end, we studied the effects of the PPARgamma ligands 15d-PGJ(2), rosiglitazone (BRL49653), and troglitazone on Fn expression in NSCLC cells and found that they were able to inhibit Fn gene transcription. Inhibition of Fn expression by BRL49653 and troglitazone, but not by 15d-PGJ(2), was prevented by the specific PPARgamma antagonist GW-9662 and by PPARgamma small interfering RNA. Working with Fn deletion and mutated promoter constructs, we found that the region between -170 and -50 bp downstream from the transcriptional start site of the promoter was involved in PPARgamma ligand inhibition. PPARgamma ligands also diminished the phosphorylation of CREB, diminished Sp1 nuclear protein expression, and prevented the binding of these transcription factors to CRE and Sp1 sites, respectively, within the Fn promoter. In summary, our results demonstrate that PPARgamma ligands inhibit Fn gene expression in NSCLC cells through PPARgamma-dependent and -independent pathways that affect both CREB and Sp1.

  1. Bronchial artery infusion of mitomycin C in carcinoma of the lung

    SciTech Connect

    Ekholm, S.; Albrechtsson, U.; Tylen, U.

    1983-06-01

    Fifteen patients with bronchial carcinoma were treated with infusions of 10 mg Mitomycin C (MMC) in the bronchial artery feeding the tumor. The treatment was repeated three times with 2-3 weeks interval between treatments. Half of the patients then received radiation to the tumor area and mediastinum. All tumors decreased in size, complete remission occurred in two and partial remission in five patients. Survival time, however, was not prolonged and esophageal complications occurred in several patients.

  2. Conditionally replicating oncolytic adenoviral vector expressing arresten and tumor necrosis factor-related apoptosis-inducing ligand experimentally suppresses lung carcinoma progression.

    PubMed

    Li, Shudong; Qi, Zongli; Li, Huijin; Hu, Jun; Wang, Dongyang; Wang, Xin; Feng, Zhenzhen

    2015-08-01

    Current methods of treatment for lung carcinoma are ineffective for the majority of patients. Conditionally replicating adenoviruses (CRAds) represent a potential novel treatment for a number of neoplastic diseases, including lung carcinoma. The present study aimed to investigate the synergistic mechanisms underlying the anti-angiogenesis gene, arresten, and the apoptosis-inducing gene, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), in order to evaluate their therapeutic potential in lung cancer. The two genes were expressed by CRAd, which was confirmed using reverse transcription-polymerase chain reaction and western blotting. In vitro analyses demonstrated that CRAd adenoviruses are capable of selectively inhibiting A549 lung cancer cell growth and replication but not in that of healthy cells. In vivo analyses demonstrated that the infection of A549 cell lines using CRAd armed with the two genes (CRAd-arresten-TRAIL) enhanced the tumor inhibition, compared with cells infected with CRAd-arresten, CRAd-TRAIL or CRAd, and with the control group. CRAd-arresten-TRAIL may therefore be useful in the treatment of lung cancer.

  3. 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.

  4. Intrathoracic impedance monitor alarm in a patient with cardiac resynchronisation therapy and advanced lung carcinoma.

    PubMed

    Cvijić, Marta; Zižek, David; Antolič, Bor; Zupan, Igor

    2013-01-01

    The intrathoracic impedance monitor system measures impedance between the device case and the right ventricular coil and reflects intrathoracic fluid status. It is used to detect early volume overload in patients with chronic heart failure. We report a case of inappropriate activation of the intrathoracic impedance monitor alarm in a patient with epidermoid lung cancer and pleural carcinosis.

  5. Dramatic response to anti-PD-1 therapy in a patient of squamous cell carcinoma of thymus with multiple lung metastases

    PubMed Central

    Yang, Yan; Ding, Liren

    2016-01-01

    Immunotherapy directed at the programmed cell death-1 receptor (PD-1) or its ligand PD-L1 has demonstrated efficacy in some malignancies, such as metastatic melanoma and non-small-cell lung cancer (NSCLC). Compared with cytotoxic chemotherapy, radiotherapy or molecular targeted agent, it is an innovative way to treat malignancies with durable clinical responses and manageable adverse. We present a case of female patient with squamous cell carcinoma of thymus involving multiple lung metastases, who was successfully treated with anti-PD-1 monoclonal antibody, pembrolizumab. PMID:27499991

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

    PubMed Central

    Vadakara, Joseph; Borghaei, Hossein

    2012-01-01

    Chemotherapy has been the traditional backbone for the management of metastatic lung cancer. Multiple trials have shown the benefits of treatment with platinum doublets in lung cancer. This “one treatment fits all” approach was further refined by the introduction of targeted agents and discovery of subpopulations of patients who benefited from treatment with these agents. It has also become evident that certain histologic subtypes of non-small-cell lung cancer respond better to one cytotoxic chemotherapy versus others. This has led to the concept of using histology to guide therapy. With the introduction of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors and the discovery of activating mutations in the EGFR gene, further personalization of treatment for subgroups of patients has become a reality. More recently, the presence of a fusion gene, echinoderm microtubule-associated protein-like 4 – anaplastic lymphoma kinase (EML4-ALK), was identified as the driver mutation in yet another subgroup of patients, and subsequent studies have led to approval of crizotinib in this group of patients. In this article, efforts in personalizing delivery of care based on the histological subtypes of lung cancer and the role of K-RAS and EGFR mutations, EML4/ALK translocation, and ERCC1 (excision repair cross-complementing 1) and EGFR expression in choosing appropriate treatments for patients with advanced lung cancer are discussed. This article also reviews the problem of resistance to EGFR tyrosine kinase inhibitors and the ongoing trials that target novel pathways and mechanisms that are implicated in resistance. PMID:23226067

  7. Diagnostics and Treatment of Hepatocellular Carcinoma in 2016: Standards and Developments

    PubMed Central

    Trojan, Jörg; Zangos, Stephan; Schnitzbauer, Andreas A.

    2016-01-01

    Background Hepatocellular carcinoma (HCC) is a frequent complication of liver cirrhosis. Worldwide, HCC is one of the most common cancers, with a rising incidence. Methods A selective literature search was conducted, taking into account current studies, reviews, meta-analyses, and guidelines. Results The diagnosis is established either non-invasively by dynamic imaging, showing a typical contrast enhancement and wash-out, or histopathologically. Pathological diagnosis of HCC is recommended for all atypical nodules in patients with cirrhosis and for those in non-cirrhotic patients. Tumor therapy as well as treatment of the underlying chronic liver disease and/or preservation of liver function are important for the management of patients with HCC. Standard stage-adapted treatments are based on the widely applied Barcelona Clinic Liver Cancer staging system including liver resection and transplantation, interventional treatments such as thermal ablation and transarterial therapies, and systemic treatment with the tyrosine kinase inhibitor sorafenib. After failure of sorafenib, anti-angiogenic drugs, MET inhibitors, and immunotherapeutics are currently under advanced clinical investigation. Conclusion Treatment of HCC is multidisciplinary and therefore requires a close cooperation between various disciplines such as hepatology, visceral surgery, radiology, and oncology to achieve the best outcome depending on the tumor stage and degree of liver function impairment. PMID:27413729

  8. Percutaneous radiofrequency ablation of lung metastases from colorectal carcinoma under C-arm cone beam CT guidance.

    PubMed

    Amouyal, G; Pernot, S; Déan, C; Cholley, B; Scotté, F; Sapoval, M; Pellerin, O

    2017-05-29

    The aim of this study was to assess the feasibility, safety and efficacy of percutaneous radiofrequency ablation of lung metastases from colorectal carcinoma using C-arm cone beam computed tomography (CBCT) guidance. This single-center prospective observational study was performed from August 2013 to August 2016, and included consecutive patients referred for radiofrequency ablation of lung metastases from colorectal cancer. Radiofrequency ablation procedures were performed under C-arm CBCT guidance. Feasibility was assessed by probe accuracy placement, time to accurate placement and number of C-arm CBCT acquisitions to reach the target lesion. Safety was assessed by the report of adverse event graded using the common terminology criteria for adverse events (CTCAE-V4.0). Efficacy was assessed by metastases response rate using RECIST 1.1 and (18)FDG-PET-CT tumor uptake at 6months. Fifty-four consecutive patients (32 men, 22 women) with a mean age of 63±8 (SD) years (range: 51-81years) with a total of 56 lung metastasis from colorectal metastases were treated in a single session. The mean tumor diameter was 25.6±4.5 (SD)mm (range: 17-31mm). Median time to insert the needle into the target lesion was 10min (range: 5-25min). Median number of needles repositioning and C-arm CBCT acquisition per patient was 1 (range: 0-3) and 4 (range: 3-6) respectively. The accuracy for radiofrequency ablation probe placement was 2±0.2 (SD)mm (range: 0-9mm). Pneumothorax requiring chest tube placement occurred in one patient (CTCAE-V4.0 grade 3). At 6months, all patients were alive with tumor response rate of -27% and had no significant activity on the (18)FDG-PET CT follow-up. Percutaneous radiofrequency ablation of lung metastases from colorectal cancer under C-arm CBCT guidance is feasible and safe, with immediate and short-term results similar to those obtained using conventional CT guidance. Copyright © 2017 Editions françaises de radiologie. Published by Elsevier Masson SAS

  9. Unexpected remission of hepatocellular carcinoma (HCC) with lung metastasis to the combination therapy of thalidomide and cyproheptadine: report of two cases and a preliminary HCC cell line study.

    PubMed

    Feng, Yu-Min; Feng, Chin-Wen; Chen, Solomon Chih-Cheng; Hsu, Cheng-Da

    2012-10-12

    We reported two cases of hepatocellular carcinoma (HCC) with lung metastases who were treated with a combination of thalidomide and cyproheptadine. The use of cyproheptadine in these two cases was originally for skin itching. Follow-up CT images revealed a complete remission of HCC in both of them after treatment for 6 months and 6 weeks, respectively. A following experimental cell line study demonstrated that cyproheptadine effectively reduced the viability of two HCC cell lines.

  10. 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.

  11. Immunohistochemical algorithm for differentiation of lung adenocarcinoma and squamous cell carcinoma based on large series of whole-tissue sections with validation in small specimens.

    PubMed

    Rekhtman, Natasha; Ang, Daphne C; Sima, Camelia S; Travis, William D; Moreira, Andre L

    2011-10-01

    Immunohistochemistry is increasingly utilized to differentiate lung adenocarcinoma and squamous cell carcinoma. However, detailed analysis of coexpression profiles of commonly used markers in large series of whole-tissue sections is lacking. Furthermore, the optimal diagnostic algorithm, particularly the minimal-marker combination, is not firmly established. We therefore studied whole-tissue sections of resected adenocarcinoma and squamous cell carcinoma (n=315) with markers commonly used to identify adenocarcinoma (TTF-1) and squamous cell carcinoma (p63, CK5/6, 34βE12), and prospectively validated the devised algorithm in morphologically unclassifiable small biopsy/cytology specimens (n=38). Analysis of whole-tissue sections showed that squamous cell carcinoma had a highly consistent immunoprofile (TTF-1-negative and p63/CK5/6/34βE12-diffuse) with only rare variation. In contrast, adenocarcinoma showed significant immunoheterogenetity for all 'squamous markers' (p63 (32%), CK5/6 (18%), 34βE12 (82%)) and TTF-1 (89%). As a single marker, only diffuse TTF-1 was specific for adenocarcinoma whereas none of the 'squamous markers,' even if diffuse, were entirely specific for squamous cell carcinoma. In contrast, coexpression profiles of TTF-1/p63 had only minimal overlap between adenocarcinoma and squamous cell carcinoma, and there was no overlap if CK5/6 was added as a third marker. An algorithm was devised in which TTF-1/p63 were used as the first-line panel, and CK5/6 was added for rare indeterminate cases. Prospective validation of this algorithm in small specimens showed 100% accuracy of adenocarcinoma vs squamous cell carcinoma prediction as determined by subsequent resection. In conclusion, although reactivity for 'squamous markers' is common in lung adenocarcinoma, a two-marker panel of TTF-1/p63 is sufficient for subtyping of the majority of tumors as adenocarcinomas vs squamous cell carcinoma, and addition of CK5/6 is needed in only a small subset of cases

  12. Metastatic pancreatic carcinoma masquerading as cystic lung disease: a rare presentation.

    PubMed

    Stern, Emily; Huseini, Taha; Kuok, YiJin; Lake, Fiona

    2017-09-01

    This 52-year-old male ex-smoker presented with a six-month history of progressive breathlessness and weight loss. He deteriorated acutely, and was admitted with severe type 1 respiratory failure. Apart from diffuse coarse crackles on chest auscultation, physical examination was unremarkable. High-resolution computed tomography (HRCT) showed diffuse cystic changes throughout the lungs. A diagnosis of pulmonary Langerhans cell histiocytosis (PLCH) was considered. Further workup identified a coincidental pancreatic lesion of uncertain significance, which remained indeterminate on magnetic resonance imaging (MRI) and on positron emission tomography (PET). Transbronchial biopsy revealed enteric differentiated adenocarcinoma exhibiting lepidic spread, and autopsy later confirmed primary pancreatic malignancy. This case demonstrates that metastatic pancreatic malignancy can present with severe respiratory failure and masquerade as cystic lung disease.

  13. Not only for melanoma. Subcutaneous pseudoprogression in lung squamous-cell carcinoma treated with nivolumab

    PubMed Central

    Sarfaty, Michal; Moore, Assaf; Dudnik, Elizabeth; Peled, Nir

    2017-01-01

    Abstract Rationale: Pseudoprogression, that is, initial tumor growth followed by subsequent tumor regression, has been well described for immunomodulation therapy in melanoma patients. This phenomenon is not well defined in lung cancer. Nivolumab, an anti-PD-1 monoclonal antibody, was recently approved for nonsmall cell lung cancer (NSCLC) as a second-line therapy. Patient concerns and diagnosis: We present a patient with squamous NSCLC, suffering from multiple bone and subcutaneous metastases. Interventions: The patient was treated with nivolumab. Outcomes: A subcutaneous lesion in her upper back grew substantially after the first cycle of nivolumab, and later regressed, with marked improvement in all cancer sites. Lessons: Such pseudoprogression may serve to predict subsequent clinical response. PMID:28121940

  14. Inhibition of Migration and Invasion by Tet-1 Overexpression in Human Lung Carcinoma H460 Cells.

    PubMed

    Park, Si Jun; Lee, Bo Ram; Kim, Hyeng-Soo; Ji, Young Rae; Sung, Yong Hun; ShikChoi, Kwang; Park, Hum Dai; Kim, Sung-Hyun; Kim, Myoung Ok; Ryoo, Zae Young

    2016-01-01

    In the present study, we found that lung cancer cell line (H460 cells) expressing Tet1 showed higher levels of adhesion, and Tet1 inhibited H460 cell proliferation. In addition, these cells showed a significantly reduced ability of collagen degradation and Smad2/3 phosphorylation compared to controls. Furthermore, vimentin was found to be highly expressed in larger metastatic cancer area. Tet1 overexpression was reduced in the epithelial marker E-cadherin. Moreover, Tet1 repressed cancer cell metastasis in nude mice. Collectively, these findings suggest that Tet1 expression plays a critical role in metastasis of lung cancer cells by suppression of invasion and epithelial-mesenchymal transition (EMT).

  15. Combined small-cell carcinoma of the lung with quadripartite differentiation of epithelial, neuroendocrine, skeletal muscle, and myofibroblastic type.

    PubMed

    Pelosi, Giuseppe; Sonzogni, Angelica; Galetta, Domenico; Perrone, Federica; Braidotti, Paola; Manzotti, Michela; Fabbri, Alessandra; Spaggiari, Lorenzo; Veronesi, Giulia; Viale, Giuseppe

    2011-04-01

    The combined variant of small-cell lung carcinoma (SCLC) refers to the variable admixture of small cell and non-small cell carcinoma, whereas the association with sarcoma or sarcoma-like elements is exceedingly rare. A 76-year-old Caucasian man underwent right upper lobectomy with regional lymphadenectomy because of a symptomatic 7 cm-sized tumor mass. Formalin fixed-paraffin embedded material was used to highlight several differentiation cell lineages by means of immunohistochemistry, electron microscopy, and mutational assay. The tumor was discovered as being IIB stage (pT2b pN1(1/51) pM0) and featured biphasic appearance with close intermingling of SCLC (40%) and collagen-rich spindle cell sarcoma (60%). Epithelial (cytokeratins, TTF-1), neural (neurofilaments, GFAP), endocrine (chromogranin, synaptophysin, CD56), and skeletal muscle (desmin, sarcomeric actin, myogenin) markers were variably co-expressed by SCLC elements, whereas mesenchymal (vimentin), smooth muscle (actin, myosin, H-caldesmon, calponin), fibroblastic (CD10), and, more focally, skeletal muscle (desmin, sarcomeric actin and myogenin) markers wer