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Sample records for lung carcinoma standardized

  1. Potential targets for lung squamous cell carcinoma

    Cancer.gov

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

  2. Carcinoma of the lung in Lancashire coalminers.

    PubMed

    Rooke, G B; Ward, F G; Dempsey, A N; Dowler, J B; Whitaker, C J

    1979-04-01

    The prevalence at death of carcinoma of the lung in miners and ex-miners has been compared in those with and without pneumoconiosis at necropsy. The prevalence of 11.4% in the group as a whole is no greater than that in the male population in North-west England. Carcinoma of the lung was present in 62 (13.1%) of those without pneumoconiosis and in 52 (9.8%) of those with pneumoconiosis. The mean age at death of those with pneumoconiosis was 71.3 years so that they cannot be said to have died before the age at which they would have developed carcinoma. Those with progressive massive fibrosis whose mean age at death was 72 years had the lowest prevalence of carcinoma of the lung at all ages--8.4%. For reasons stated in the text this is inevitably a biased sample. The number of those without pneumoconiosis is probably lower than the true figure because the deaths of miners and ex-miners in whom there is no suspicion of lung disease may not have been reported to the coroner or to the pneumoconiosis medical panel. There appears to be no positive link between carcinoma of the lung and pneumoconiosis. There is a surprisingly high number of smokers and ex-smokers among these miners, and this appears to have more relevance to the prevalence of carcinoma of the lung than does pneumoconiosis.

  3. Clear cell carcinoma of the lung.

    PubMed Central

    Edwards, C; Carlile, A

    1985-01-01

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

  4. Pulmonary hyalinizing granuloma mimicking lung carcinoma.

    PubMed

    Basoglu, A; Findik, S; Celik, B; Yildiz, L

    2006-06-01

    Pulmonary hyalinizing granuloma has rarely been reported and is a benign entity of unknown origin. The chest radiograph reveals multiple and frequently bilateral pulmonary nodules. We describe a patient with pulmonary hyalinizing granuloma who presented with a central mass in the left lung mimicking lung carcinoma. PMID:16755455

  5. Diagnosing Lung Carcinomas with Optical Coherence Tomography

    PubMed Central

    Hariri, Lida P.; Mino-Kenudson, Mari; Lanuti, Michael; Miller, Alyssa J.; Mark, Eugene J.

    2015-01-01

    Rationale: Lung carcinoma diagnosis on tissue biopsy can be challenging because of insufficient tumor and lack of architectural information. Optical coherence tomography (OCT) is a high-resolution imaging modality that visualizes tissue microarchitecture in volumes orders of magnitude larger than biopsy. It has been proposed that OCT could potentially replace tissue biopsy. Objectives: We aim to determine whether OCT could replace histology in diagnosing lung carcinomas. We develop and validate OCT interpretation criteria for common primary lung carcinomas: adenocarcinoma, squamous cell carcinoma (SCC), and poorly differentiated carcinoma. Methods: A total of 82 ex vivo tumor samples were included in a blinded assessment with 3 independent readers. Readers were trained on the OCT criteria, and applied these criteria to diagnose adenocarcinoma, SCC, or poorly differentiated carcinoma in an OCT validation dataset. After a 7-month period, the readers repeated the training and validation dataset interpretation. An independent pathologist reviewed corresponding histology. Measurements and Main Results: The average accuracy achieved by the readers was 82.6% (range, 73.7–94.7%). The sensitivity and specificity for adenocarcinoma were 80.3% (65.7–91.4%) and 88.6% (80.5–97.6%), respectively. The sensitivity and specificity for SCC were 83.3% (70.0–100.0%) and 87.0% (75.0–96.5%), respectively. The sensitivity and specificity for poorly differentiated carcinoma were 85.7% (81.0–95.2%) and 97.6% (92.9–100.0%), respectively. Conclusions: Although these results are encouraging, they indicate that OCT cannot replace histology in the diagnosis of lung carcinomas. However, OCT has potential to aid in diagnosing lung carcinomas as a complement to tissue biopsy, particularly when insufficient tissue is available for pathology assessment. PMID:25562183

  6. Obstructive jaundice in small cell lung carcinoma.

    PubMed

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

    2015-08-01

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

  7. Higher mortality risk of lungs carcinoma in vineyard sprayers.

    PubMed

    Santić, Zarko; Puvacić, Zlatko; Radović, Svjetlana; Puvacić, Sandra

    2005-05-01

    This study investigated mortality rate of lungs carcinoma in professional vineyard sprayers. Clinical investigation was performed in 187 professional vineyard sprayers who had been exposed to the inhalation of the particles of Bordeaux mixture for 24 years on average. Bordeaux Mixture is used for prevention against mildew attacking vineyards. The control group was composed of 187 inhabitants of the same area who did not have any contact with the mentioned substance. A cytological investigation of the sputum specimens obtained from 104 tested inhabitants was performed. The sputum specimens were stained with standard haematoxylin-eosin method and also with special method (rubeanic acid) to prove the incidence of copper granules in macrophages. The findings show a considerable statistical difference in the frequency of occurrence of lungs carcinoma between the group of vineyard sprayers smokers and the control group (X2=4.77,p<0.01). The risk of lungs carcinoma in the vineyard sprayers was three times higher compared to the risk of smokers in the control group, with a statistical probability of 95% in the scope from 1.16lungs carcinoma in the professional vineyard sprayers is significantly higher (p<0.01) compared to the risk in the control group.

  8. 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.

  9. Carcinoma of the lungs causing enlarged kidneys.

    PubMed

    Srisung, Weeraporn; Mankongpaisarnrung, Charoen; Warraich, Irfan; Sotello, David; Yarbrough, Shannon; Laski, Melvin

    2015-04-01

    Bilateral enlarged kidneys can be caused by a number of conditions. Renal metastasis is included in the differential diagnosis. We report a case of a 67-year-old woman with a 6-month history of productive cough and unintentional weight loss. Cavitary pulmonary lesions and bilateral enlarged kidneys were noted on imaging studies. Hematuria, azotemia, and proteinuria were present. Renal biopsy showed squamous carcinoma cells invading normal-appearing glomeruli and atrophic tubules. The invasive squamous cells stained negative for CK7 and CK 20. Lung biopsy confirmed squamous cell carcinoma. Our case shows that in patients with renal enlargement, even with the absence of a focal mass, renal metastasis should be considered, especially in those with suspected or diagnosed malignancy elsewhere. PMID:25829660

  10. Silica, pneumoconiosis and carcinoma of the lung

    SciTech Connect

    Heppleston, A.G.

    1985-01-01

    The author explains the possible relationship between exposure to mineral dust with a high silica content and the development of bronchogenic carcinoma. Studies to date accept that lung cancer is a risk associated with exposure to siliceous dust. The author has sought to establish arguments to refute this theory and has accumulated observations based on practical experiences with miners which indicate that silica does not possess this carcinogenic role. The above mentioned observations take the form of medical examinations or autopsies on mine workers in different countries. 72 references.

  11. 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

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

    PubMed

    Dorantes-Heredia, Rita; Ruiz-Morales, José Manuel; Cano-García, Fernando

    2016-08-01

    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

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

    PubMed

    Dorantes-Heredia, Rita; Ruiz-Morales, José Manuel; Cano-García, Fernando

    2016-08-01

    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.

  14. 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. PMID:21802893

  15. 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.

  16. Ectopic ACTH Production in Carcinoma of the Lung

    PubMed Central

    Gewirtz, George; Yalow, Rosalyn S.

    1974-01-01

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

  17. Giant gingival pseudoepitheliomatous hyperplasia in lung squamous cell carcinoma.

    PubMed

    Xiang, Guolin; Long, Xing; Han, Qianchao; Tian, Lihua

    2012-07-01

    We here describe a case of giant primary gingival pseudoepitheliomatous hyperplasia in a 53-year-old Chinese male patient with lung squamous cell carcinoma (SCC). The pathogenesis of the lesion and the deferential diagnosis from invasive SCC are also discussed. To our knowledge, such a hugeous primary pseudoepitheliomatous hyperplasia of the gingiva accompanied with lung SCC is unusual.

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

    PubMed

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

    2015-09-01

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

  19. Human papillomavirus in lung carcinomas among three Latin American countries.

    PubMed

    Castillo, Andres; Aguayo, Francisco; Koriyama, Chihaya; Shuyama, Karem; Akiba, Suminori; Herrera-Goepfert, Roberto; Carrascal, Edwin; Klinge, German; Sánchez, Juvenal; Eizuru, Yoshito

    2006-04-01

    The presence of human papillomavirus (HPV) genome in lung carcinomas has been reported worldwide but its frequency varies from country to country. We examined HPV genome in 36 lung carcinomas, consisting of 14 squamous cell carcinomas, 13 adenocarcinomas, and 9 small cell carcinomas, collected from Colombia, Mexico and Peru. PCR analysis using GP5+/GP6+ primers, combined with Southern blot hybridization, found the presence of HPV genome in 10 (28%) of 36 cases. This percentage is similar to the value of 22% reported by Syrjänen, who conducted a meta-analysis of nearly 2500 lung carcinomas examined to date. Genotype analysis revealed that the most predominant genotype was HPV-16 (7 cases), followed by HPV-18 (2 cases) and HPV-33 (1 case). HPV-16 was more frequently found among female than male cases (P=0.008) but was not detected in any adenocarcinoma cases. On the other hand, HPV-18 and HPV-33 were detected only among male cases. These HPV genotypes were detected only in adenocarcinomas, and all the HPV genotypes detected in this histological type were HPV-18 or HPV-33. The frequency of HPV-16 positive cases among all the HPV positive cases differed in the sexes (P=0.033) and differed in the three histological types (P=0.017). The presence of HPV tended to be more frequent in well-differentiated tumors when squamous cell carcinomas and adenocarcinomas were combined. However, it was not statistically significant (P=0.093). Neither p16 nor p53 expression in carcinoma cells was related to the proportion of HPV-positive cases. In conclusion, high-risk HPV DNA was detected in 28% of lung carcinomas. The predisposition of HPV-16 to female cases and to non-adenomatous carcinomas warrants further investigation. PMID:16525675

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

    PubMed

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

    2016-08-01

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

  1. Interstitial lung disease associated with vindesine and radiation therapy for carcinoma of the lung

    SciTech Connect

    Bott, S.J.; Stewart, F.M.; Prince-Fiocco, M.A.

    1986-07-01

    Diffuse interstitial lung disease and pulmonary fibrosis occurred after the use of vindesine and radiation therapy in a patient with squamous cell carcinoma of the lung. Clinical improvement occurred after the drug was discontinued and corticosteroid therapy was initiated. Review of the literature reveals no previously reported cases of pulmonary toxicity due to vindesine when used alone or in combination with other therapeutic modalities.

  2. Accuracy of classifying poorly differentiated non-small cell lung carcinoma biopsies with commonly used lung carcinoma markers.

    PubMed

    Zachara-Szczakowski, Susanna; Verdun, Tyler; Churg, Andrew

    2015-05-01

    Immunohistochemical (IHC) staining is an important adjunct to the classification of non-small cell lung carcinoma (NSCLC). Several studies have used tissue microarrays derived from resection specimens to evaluate the accuracy of IHC staining for classifying NSCLC, but few have used actual biopsies of poorly differentiated carcinomas, and the question of how often biopsy IHC in such tumors leads to the correct classification has received little attention. We identified 40 cases of NSCLC that, on biopsy, could not be subclassified by morphology and that had subsequent resection specimens. TTF-1, napsin, p63/p40, and CK5 or a subset thereof were used for IHC classification. Of the 40 cases classified by IHC on biopsy, 33 (82%) had no change in diagnosis after resection. Of the remaining 7 cases, 3 were classified as NSCLC--not otherwise specified on biopsy and subclassified as either adenocarcinoma or squamous cell carcinoma (SCC) on the surgical specimen. One adenocarcinoma biopsy was reclassified as pleomorphic carcinoma. Two SCCs were changed to adenosquamous carcinoma, and 1 SCC was changed to large cell lung carcinoma. Only 1 antibody pair (2%) was discordant between biopsy, and almost all reclassifications were done based on morphologic features rather than change in IHC pattern. We conclude that IHC staining allows accurate subclassification of poorly differentiated NSCLCs on small lung biopsies in most cases, but there is still a substantial "miss" rate (here, 18%). Surgical resection specimens allow further subclassification, mainly due to architectural features not present in the biopsies.

  3. 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.

  4. Mucoepidermoid carcinoma of lung: a case report.

    PubMed

    Khadilkar, Urmila N; Kumar, Suneet; Prabhu, Prashant P; Kamath, Madhav

    2007-07-01

    Mucoepidermoid lung tumours are uncommon neoplasms comprising of 0.2% of all the lung tumours and historically included under the term bronchial adenomas. This is a case report of a bronchial tumour in the hilar region present since 3 years. The neoplasm could be easily classified as a mucoepidermoid tumour of low malignant potential, as it resembled the histologically identical lesion in the main salivary glands. The case is reported for its rarity and for the histological evaluation of the malignant potential in an apparently clinically benign neoplasm.

  5. 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.

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

    PubMed

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

    2016-04-01

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

  7. Psychosocial factors and smoking as risk factors in lung carcinoma.

    PubMed

    Blohmke, M; von Engelhardt, B; Stelzer, O

    1984-01-01

    In a retrospective study as part of a larger study 419 male patients with bronchial carcinoma were questioned by means of a 'biographical questionnaire' concerning their life history, their personality, and their approach to life. Furthermore questions with regard to their smoking habits (tobacco smoke condensate exposure) were asked. Only patients who smoked cigarettes regularly were involved in the interrogation and the results were compared with those of smoking healthy controls and patients with non-malignant lung diseases (N = 162). For each pair group-controls a discriminant analysis was carried out. By reclassification a correct assignment of approx. 62% in each case could then be obtained. In addition, the answer pattern of the carcinoma patients was compared with a group of patients with non-malignant lung diseases. The results obtained were similar to those of the comparison with the healthy control group.

  8. KLN205--a murine lung carcinoma cell line.

    PubMed

    Kaneko, T; LePage, G A; Shnitka, T K

    1980-10-01

    KLN205 cells, a cloned cell line established from the Nettesheim lung carcinoma, grow in various synthetic media such as MEM, Fisher's or Roswell Park Memorial Institute Medium (RPMI) with the addition of 5 to 20% fetal bovine serum (FBS), calf-serum (CS) or horse serum (HS). They grow optimally in minimum Eagle's medium plus nonessential amino acids (NEAA) plus 5 to 10% FBS or HS. The cells are transplantable to DBA/2, BDF1, AKD2F1, and BALB/c, but not to C3H/He or ICR mice. The growth curves, plating efficiency, ultrastructural characteristics, modal number of chromosomes and transplantability to mice of various strains are almost the same for early and late passage of cells passaged in vitro. These parameters for 16th and 36th passages were: doubling time, 31 and 33 hr; plating efficiency, 12.4 +/- 1.2 and 14.6 +/- 2.6%; modal number of chromosomes, 73 and 76; lung colony formation in DBA/2, 50 and 45.9/mouse; and subcutaneous tumor diameter 24.5 and 27.4 mm, respectively. Only the numbers of lung colonies formed in BDF1 mice were different: 24.4/mouse with 16th passage cells, and 10.2/mouse with 36th passage cells. The results suggest that KLN205 is a relatively stable cultured cell line through 36 passages. As was expected, immunosuppression by higher concentrations of triaminolone acetonide (TA) enhanced lung colony formation in BDF1 mice. On the other hand, a low concentration of TA inhibited lung colony formation in DBA/2 mice, which was unexpected. These results suggest that KLN205 offers a model for investigations on metastases to lungs as well as chemotherapy for lung carcinoma.

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

    PubMed

    Fan, Tao; Song, Ying-Jie

    2016-06-01

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

  10. 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.

  11. Standardized beam bouquets for lung IMRT planning.

    PubMed

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

    2015-03-01

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

  12. Standardized beam bouquets for lung IMRT planning

    PubMed Central

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

    2015-01-01

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

  13. Mucoepidermoid carcinoma of the conjunctiva with lung metastasis.

    PubMed

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

    2015-05-01

    A 36-year-old lady presented with redness and decreased vision in right eye since 6 months. She was earlier diagnosed of cavitary lung lesion, presumed secondary to tuberculosis and treated with anti-tubercular treatment for 4 months. Examination of affected right eye revealed nil light perception, conjunctival congestion with an exuberant mass in the inferotemporal bulbar conjunctiva, proptosis, iris neovascularization, 360° closed angles, intraocular pressure of 48 mm Hg, exudative retinal detachment, uveal mass and orbital extension. A diagnostic needle biopsy of uveal mass revealed malignant cells. Computed tomography-guided lung biopsy revealed squamous cell carcinoma (SCC), indicating metastatic spread from the orbit. She underwent lid-sparing exenteration of the right eye. Histopathological examination of the orbital tissue revealed mucoepidermoid carcinoma arising from the conjunctiva with extensive invasion into the orbital tissue, muscle fibers, sclera, choroid and optic nerve. Multiple tumor emboli were seen in the lumen of orbital blood vessels. In conclusion, mucoepidermoid carcinoma of the conjunctiva is a rare, aggressive variant of SCC. Early intervention is essential to prevent intraocular invasion and systemic metastasis. PMID:26139812

  14. Lung carcinoma with rhabdoid component. A series of seven cases associated with uncommon types of non-small cell lung carcinomas and alveolar entrapment.

    PubMed

    Izquierdo-Garcia, Francisco M; Moreno-Mata, Nicolás; Herranz-Aladro, María Luisa; Cañizares, Miguel Angel; Alvarez-Fernandez, Emilio

    2010-10-01

    Rhabdoid tumor, included in the WHO classification among large cell carcinomas of the lung, is an uncommon type of lung carcinoma with poor prognosis. We report a series of 7 cases of lung carcinomas with rhabdoid component in 10% and 80% of the tumor. The associated tumor was adenocarcinoma in 3 cases--one of them with focal micropapillary pattern--large cell carcinoma in 2 cases, squamous cell carcinoma in 1 case and pleomorphic carcinoma in 1 case. Two adenocarcinomas showed a focal spindle cell component. Micropapillary and pleomorphic types had not been reported before as a component associated with rhabdoid carcinomas. All cases were positive for vimentin, and AE1/AE3 cytokeratin and 5 cases for cytokeratin 7. All cases were negative for muscle and endothelial markers and for chromogranin A. Synaptophysin was focally positive only in one case. Alveolar trapping inside the tumor was present in 3 cases--a phenomenon not well studied in lung carcinomas and also not reported in tumors with rhabdoid component. Five patients died because of the tumor within 2 to 31 months after diagnosis, one of myocardial infarction and only one is alive and disease free 123 months after the diagnosis. In summary, we describe 7 new cases of this uncommon lung tumor with aggressive clinical course, associated with infrequent histological types in nonrhabdoid component and with alveolar trapping, a nondescribed finding.

  15. 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.

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

    PubMed

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

    2016-01-01

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

  17. 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

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

    SciTech Connect

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

    2009-06-01

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

  19. Current role of surgery in small cell lung carcinoma

    PubMed Central

    Koletsis, Efstratios N; Prokakis, Christos; Karanikolas, Menelaos; Apostolakis, Efstratios; Dougenis, Dimitrios

    2009-01-01

    Small cell lung carcinoma represents 15–20% of lung cancer. Is is characterized by rapid growth and early disseminated disease with poor outcome. For many years surgery was considered a contraindication in Small Cell Lung Cancer (SCLC) since radiotherapy and chemoradiotherapy were found to be more efficient in the management of these patients. Never the less some surgeons continue to be in favor of surgery as part of a combined modality treatment in patients with SCLC. The revaluation of the role of surgery in this group of patients is based on clinical data indicating a much better prognosis in selected patients with limited disease (T1-2, N0, M0), the high rate of local recurrence after chemoradiotherapy with surgery considered eventually more efficient in the local control of the disease and the fact that surgery is the most accurate tool to access the response to chemotherapy, identify carcinoids misdiagnosed as SCLC and treat the Non Small Cell Lung Cancer component of mixed tumors. Performing surgery for local disease SCLC requires a complete preoperative assessment to exclude the presence of nodal involvement. In stage I surgery must always be followed by adjuvant chemotherapy, while in stage II and III surgery must be planned only in the context of clinical trials and after a pathologic response to induction chemoradiotherapy has been confirmed. Prophylactic cranial irradiation should be used to reduce the incidence of brain metastasis PMID:19589150

  20. Low p53 protein expression in salivary gland tumours compared with lung carcinomas.

    PubMed

    Soini, Y; Kamel, D; Nuorva, K; Lane, D P; Vähäkangas, K; Pääkkö, P

    1992-01-01

    Fifty-one salivary gland tumours (23 pleomorphic adenomas, 5 Warthin's tumours, 12 mucoepidermoid carcinomas, 7 adenoid cystic carcinomas, 3 undifferentiated carcinomas and 1 acinic cell tumour) and 27 lung carcinomas (18 squamous cell carcinomas) were analysed immunohistochemically for the expression of p53 nuclear phosphoprotein. Eight out of 51 (16%) salivary gland tumours were p53 positive. Three of these were benign and 5 malignant. All 3 benign salivary gland tumours were pleomorphic adenomas and expressed only occasional nuclear positivity with less than 1% of tumour cells positive. Of the 5 p53-positive malignant tumours, 3 were mucoepidermoid carcinomas and 2 undifferentiated carcinomas. The malignant salivary gland tumours expressed more than 1% of positive nuclei in every case. Seventeen lung carcinomas were p53 positive (63%). Thirteen of these were squamous cell carcinomas, 3 were adenocarcinomas and 1 small cell lung carcinoma. The results show that mutations of the p53 gene may be infrequent in salivary gland tumours when compared with lung carcinomas. The relatively indolent course of some histological types of malignant salivary gland tumours could be associated with the preservation of the non-mutated p53 gene in most of these tumours. The presence of p53 positivity in some pleomorphic adenomas might, on one hand, suggest that p53 gene alterations are also present in these tumours; on the other hand, the accumulation of the p53 protein in these tumours might also be due to some unknown mechanism, not necessarily related to p53 gene mutation.

  1. 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.

  2. 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

  3. Metastasis of carcinoma of the lung to a carotid body paraganglioma.

    PubMed

    Bury, Yvonne; Green, Richard; Jain, Mona; Moor, James

    2012-04-04

    Tumour-to-tumour metastasis is a rare phenomenon, but has been described in the literature in just over 100 cases. It can be particularly puzzling for the reporting pathologists, when encountered unexpectedly in a tumour showing abrupt transition from the usual morphology to another unusual pattern. The literature reports a variety of combinations with carcinoma-to-carcinoma being the most common; and renal cell carcinomas appear to the most common recipient tumours with common donor tumours being breast, lung and renal cell carcinomas. The authors report a case of poorly-differentiated lung carcinoma metastasising into a carotid body paraganglioma. Our case is unique and in our knowledge the first described case of carotid body paraganglioma with metastasis from a lung primary. To the best of our knowledge this is the first report of this interesting biological phenomenon in this combination.

  4. Properties of lewis lung carcinoma cells surviving curcumin toxicity.

    PubMed

    Yan, Dejun; Geusz, Michael E; Jamasbi, Roudabeh J

    2012-01-01

    The anti-inflammatory agent curcumin can selectively eliminate malignant rather than normal cells. The present study examined the effects of curcumin on the Lewis lung carcinoma (LLC) cell line and characterized a subpopulation surviving curcumin treatments. Cell density was measured after curcumin was applied at concentrations between 10 and 60 μM for 30 hours. Because of the high cell loss at 60 μM, this dose was chosen to select for surviving cells that were then used to establish a new cell line. The resulting line had approximately 20% slower growth than the original LLC cell line and based on ELISA contained less of two markers, NF-κB and ALDH1A, used to identify more aggressive cancer cells. We also injected cells from the original and surviving lines subcutaneously into syngeneic C57BL/6 mice and monitored tumor development over three weeks and found that the curcumin surviving-line remained tumorigenic. Because curcumin has been reported to kill cancer cells more effectively when administered with light, we examined this as a possible way of enhancing the efficacy of curcumin against LLC cells. When LLC cells were exposed to curcumin and light from a fluorescent lamp source, cell loss caused by 20 μM curcumin was enhanced by about 50%, supporting a therapeutic use of curcumin in combination with white light. This study is the first to characterize a curcumin-surviving subpopulation among lung cancer cells. It shows that curcumin at a high concentration either selects for an intrinsically less aggressive cell subpopulation or generates these cells. The findings further support a role for curcumin as an adjunct to traditional chemical or radiation therapy of lung and other cancers.

  5. EGFR mutation status in brain metastases of non-small cell lung carcinoma.

    PubMed

    Burel-Vandenbos, Fanny; Ambrosetti, Damien; Coutts, Michael; Pedeutour, Florence

    2013-01-01

    Brain metastases are a frequent and grave complication of non-small cell lung carcinoma (NSCLC). The prognosis is generally poor, despite standard therapy based on surgery and radiotherapy. A degree of understanding of the molecular basis of tumors has led to the development of targeted agents with promising initial findings for the treatment of NSCLC. EGFR mutations have been identified which are associated with significant sensitivity to EGFR tyrosine kinase inhibitors (TKI) and correlate with improved outcome in patients with NSCLC who are treated with these agents. The adoption of treatment tailored to the genetic make-up of individual tumors could lead to substantial therapeutic improvements, and such targeted therapy might be considered as a therapeutic option for brain metastases in the future. We review current knowledge about EGFR mutation status in the specific context of brain metastasis: its association with the response of brain metastases to TKI, its prevalence in brain metastases, and the correlation between mutation status in metastases as compared to the corresponding primary lung carcinoma. PMID:23086434

  6. Quantitative nuclear texture features analysis confirms WHO classification 2004 for lung carcinomas.

    PubMed

    Schmid, Katharina; Angerstein, Nina; Geleff, Silvana; Gschwendtner, Andreas

    2006-03-01

    The purpose of this study was to discriminate the main subsets of lung carcinomas of the WHO classification of 2004 by nuclear chromatin texture feature analysis. Our collective comprised 56 typical and 19 atypical carcinoids, 37 small-cell carcinomas, 15 large-cell neuroendocrine carcinomas, 42 adenocarcinomas, and 26 squamous cell carcinomas. After Feulgen staining, cell nuclei were automatically measured using a high-resolution image analyser (CytoSavant Oncometrics, Vancouver, BC, Canada). Texture features describing the granularity and the compactness of the nuclear chromatin were extracted for calculation of classification rules, which allowed the discrimination of different tumor groups. By applying the classification rule that described the granularity of the nuclear chromatin (defined by four different parameters) small-cell and non-small-cell lung carcinoma could correctly be discriminated in 93%. No significant discrimination was possible between the different subtypes of large-cell carcinomas, including large-cell neuroendocrine carcinoma. When using compactness of chromatin (defined by four texture parameters) as a means of discrimination, carcinoids and non-small-cell lung carcinomas were correctly distinguished in 92%. No significant discrimination between neuroendocrine tumors was achieved though. Our findings are in accordance with the new WHO classification of 2004: neuroendocrine tumors of the lung are now classified according only to their mitotic counts and presence of necrosis but not by their morphology; their discrimination by the means of nuclear image analysis is not sufficient and therefore not appropriate any longer. PMID:16462732

  7. Squamous cell carcinoma lung: Presented with bilateral lower limb deep venous thrombosis with gangrene formation

    PubMed Central

    Saha, Kaushik; Sengupta, Amitabha; Patra, Anupam; Jash, Debraj

    2013-01-01

    Bilateral venous thrombosis due to underlying malignancy is a rare entity. It is worthy to search for malignancy in patients of bilateral venous gangrene. Our patient presented with severe bilateral leg pain as a result of venous gangrene. There was associated left sided massive pleural effusion with scalp nodule. Fine needle aspiration cytology of scalp nodule revealed metastatic squamous cell carcinoma and fiber optic bronchoscopy guided biopsy from growth at left upper lobe bronchus confirmed the case as squamous cell carcinoma lung. It was rare for squamous cell carcinoma lung to present as bilateral venous gangrene with anticardiolipin antibody negative. PMID:24455526

  8. 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

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

    SciTech Connect

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

    1990-07-01

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

  10. A network-based method for identifying prognostic gene modules in lung squamous carcinoma

    PubMed Central

    Zhang, Kaitai; Wang, Guiqi; Zhang, Lei; An, Ning; Cheng, Shujun

    2016-01-01

    Similarities in gene expression between both developing embryonic and precancerous tissues and cancer tissues may help identify much-needed biomarkers and therapeutic targets in lung squamous carcinoma. In this study, human lung samples representing ten successive time points, from embryonic development to carcinogenesis, were used to construct global gene expression profiles. Differentially expressed genes with similar expression in precancerous and cancer samples were identified. Using a network-based greedy searching algorithm to analyze the training cohort (n = 69) and three independent testing cohorts, we successfully identified a significant 22-gene module in which expression levels were correlated with overall survival in lung squamous carcinoma patients. PMID:26919109

  11. 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.

  12. Paraneoplastic neurologic disorders in small cell lung carcinoma

    PubMed Central

    Woodhall, Mark; Chapman, Caroline; Nibber, Anjan; Waters, Patrick; Vincent, Angela; Lang, Bethan; Maddison, Paul

    2015-01-01

    Objective: To determine the frequency and range of paraneoplastic neurologic disorders (PNDs) and neuronal antibodies in small cell lung carcinoma (SCLC). Methods: Two hundred sixty-four consecutive patients with biopsy-proven SCLC were recruited at the time of tumor diagnosis. All patients underwent full neurologic examination. Serum samples were taken prior to chemotherapy and analyzed for 15 neuronal antibodies. Thirty-eight healthy controls were analyzed in parallel. Results: PNDs were quite prevalent (n = 24, 9.4%), most frequently Lambert-Eaton myasthenic syndrome (3.8%), sensory neuronopathy (1.9%), and limbic encephalitis (1.5%). Eighty-seven percent of all patients with PNDs had antibodies to SOX2 (62.5%), HuD (41.7%), or P/Q VGCC (50%), irrespective of their syndrome. Other neuronal antibodies were found at lower frequencies (GABAb receptor [12.5%] and N-type VGCC [20.8%]) or very rarely (GAD65, amphiphysin, Ri, CRMP5, Ma2, Yo, VGKC complex, CASPR2, LGI1, and NMDA receptor [all <5%]). Conclusions: The spectrum of PNDs is broader and the frequency is higher than previously appreciated, and selected antibody tests (SOX2, HuD, VGCC) can help determine the presence of an SCLC. PMID:26109714

  13. Partial atrial resection in advanced lung carcinoma with and without cardiopulmonary bypass.

    PubMed Central

    Shirakusa, T; Kimura, M

    1991-01-01

    Combined pneumonectomy and partial resection of the left atrium was performed in 12 patients with advanced lung carcinoma (T3 and T4 in the new UICC classification). In the eight patients with a T3 lung carcinoma intrapericardial atrial resection with vascular clamping was carried out; four of the patients died within a year. The remaining four patients had a T4 tumour and underwent removal of the right lung and part of the left atrium under total cardiopulmonary bypass. One patient died shortly after the operation from cerebral and cerebellar infarction, and one died 11 months later from brain metastases. Two are alive and well. Complete resection appears to offer a chance for longer survival in patients with advanced lung carcinoma that extends directly into the intrapericardial pulmonary vessels or atrium. Images PMID:1652165

  14. 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

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

    PubMed

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

    2016-01-01

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

  16. Colonic Metastases From Lung Carcinoma: A Case Report and Review of the Literature

    PubMed Central

    Gonzalez-Tallon, Ana Isabel; Vasquez-Guerrero, Jorge; Garcia-Mayor, Maria Angeles

    2013-01-01

    Lung cancer is the most frequent cause of cancer death in the world. Although about 50% of lung cancers have distant metastases at the time of diagnosis, gastrointestinal metastasis has rarely been described. The most common metastatic site is the small bowel, whereas, colonic metastases are very rare. This report presents a clinical case of a 68-year-old male with a previous diagnosis of non-microcytic lung carcinoma (T4, N2, M1), stage IV, who presented rectorrhagia at the emergency. Colonoscopy showed many ulcerated tumors along the colon and histology proved that these lesions were metastases of primitive lung carcinoma. Gut metastasis from the lung is uncommon but we have to be aware of it in patients who present gastrointestinal symptoms.

  17. 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.

  18. 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.

  19. Lung endothelial dipeptidyl peptidase IV is an adhesion molecule for lung-metastatic rat breast and prostate carcinoma cells

    PubMed Central

    1993-01-01

    Attachment of circulating tumor cells to endothelial cell adhesion molecules restricted to select vascular compartments is thought to be responsible for site-specific metastasis. Lung-metastatic rat R3230AC- MET breast and RPC-2 prostate carcinoma cells bound outside-out endothelial cell membrane vesicles, prepared by perfusion of the rat lung vasculature with a low-strength formaldehyde solution, in significantly higher numbers than their nonmetastatic counterparts R3230AC-LR and RPC-LR. In contrast, vesicles derived from the vasculature of a nonmetastasized organ (e.g., hind leg muscle) showed no binding preference for either of the four tumor cell lines. Lung- derived endothelial vesicles were used here to generate mAbs against lung endothelial cell adhesion molecules. The first group of mice were actively immunized against lung endothelial vesicles, whereas the second group was injected with syngeneic mouse antiserum against leg endothelial vesicles before active immunization with lung endothelial vesicles. 17 hybridoma supernatants obtained from the two fusions bound lung vesicles with at least a 10-fold higher affinity than leg vesicles. Seven (four obtained by a passive/active immunization protocol) stained rat capillary endothelia. One mAb, mAb 8.6A3, inhibited specific adhesion of lung-derived vesicles to lung-metastatic breast and prostate carcinoma cells. Purification of the antigen (endothelial cell adhesion molecule) from rat lung extracts revealed a protein with a 110-kD mol wt. NH2-terminal sequencing established identity with dipeptidyl peptidase IV which had been reported to serve as a fibronectin-binding protein. These results indicate that vesicles obtained from in situ perfused organs are a convenient immunogen for the production of antibodies to compartment-specific endothelial cell surface molecules, and reinforce the concept that endothelial cell surface components are selectively recognized by circulating cancer cells during metastasis

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

    PubMed

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

    2009-07-01

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

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

    PubMed

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

    2016-03-01

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

  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. Differential sensitivity to apoptosome apparatus activation in non-small cell lung carcinoma and the lung

    PubMed Central

    MORAVCIKOVA, ERIKA; KREPELA, EVZEN; PROCHAZKA, JAN; BENKOVA, KAMILA; PAUK, NORBERT

    2014-01-01

    The intrinsic apoptosis pathway represents an important mechanism of stress-induced death of cancer cells. To gain insight into the functional status of the apoptosome apparatus in non-small cell lung carcinoma (NSCLC), we studied its sensitivity to activation, the assembly of apoptosome complexes and stability of their precursors, and the importance of X-linked inhibitor of apoptosis (XIAP) in the regulation of apoptosome activity, using cell-free cytosols from NSCLC cell lines and NSCLC tumours and lungs from 62 surgically treated patients. Treatment of cytosol samples with cytochrome c (cyt-c) and dATP induced proteolytic processing of procaspase-9 to caspase-9, which was followed by procaspase-3 processing to caspase-3, and by generation of caspase-3-like activity in 5 of 7 studied NSCLC cell lines. Further analysis demonstrated formation of high-Mr Apaf-1 complexes associated with cleaved caspase-9 in the (cyt-c + dATP)-responsive COLO-699 and CALU-1 cells. By contrast, in A549 cells, Apaf-1 and procaspase-9 co-eluted in the high-Mr fractions, indicating formation of an apoptosome complex unable of procaspase-9 processing. Thermal pre-treatment of cell-free cytosols in the absence of exogenous cyt-c and dATP lead to formation of Apaf-1 aggregates, unable to recruit and activate procaspase-9 in the presence of cyt-c and dATP, and to generate caspase-3-like activity. Further studies showed that the treatment with cyt-c and dATP induced a substantially higher increase of caspase-3-like activity in cytosol samples from NSCLC tumours compared to matched lungs. Tumour histology, grade and stage had no significant impact on the endogenous and the (cyt-c + dATP)-induced caspase-3-like activity. Upon addition into the cytosol, the XIAP-neutralizing peptides AVPIAQK and ATPFQEG only moderately heightened the (cyt-c + dATP)-induced caspase-3-like activity in some NSCLC tumours. Taken together, the present study provides evidence that the apoptosome apparatus is

  4. [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.

  5. Octreotide acetate therapy for hypercalcemia complicating small cell carcinoma of the lung.

    PubMed

    Dainer, P M

    1991-10-01

    I have reported a rare case of hypercalcemia associated with small cell carcinoma of the lung. Our patient initially had small cell carcinoma of the right bronchial orifice, with metastases to the mediastinum and the lumbar vertebrae. Complete remission was achieved with chemotherapy over the next 3 years, but then three metastatic foci were found in the brain. Subsequently, recurrent small cell carcinoma was identified in the lung, and chemotherapy was resumed. The patient's condition deteriorated over the following 2 months. When intravenous saline failed to control hypercalcemia, octreotide acetate was given. The serum calcium level returned to normal and remained stable, without any other intervention, until the day after octreotide therapy was discontinued. I have discussed hypercalcemia due to bronchogenic carcinoma in terms of incidence in relation to histologic type, mechanisms of pathogenesis, and current treatment methods.

  6. Spontaneous regression in advanced squamous cell lung carcinoma

    PubMed Central

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

    2016-01-01

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

  7. Lung carcinoma and malignant mesothelioma in patients exposed to Thorotrast: incidence, histology and p53 status.

    PubMed

    Andersson, M; Wallin, H; Jönsson, M; Nielsen, L L; Visfeldt, J; Vyberg, M; Bennett, W P; De Benedetti, V M; Travis, L B; Storm, H H

    1995-11-01

    In a previous registry-based survey of 999 patients injected with alpha-emitting 232ThO2 (Thorotrast), we identified elevated risks for lung carcinoma and malignant mesothelioma. Since injected Thorotrast is retained lifelong mostly in liver, spleen and lymph nodes, the mesothelial surfaces of these organs are constantly irradiated. Thorotrast-administered patients also perpetually exhale 220Rn, a 232Th-daughter. Study of Thorotrast-exposed patients may, therefore, provide data with regard to carcinogenicity of radon exposure, a current public health concern, as well as the pathogenesis of malignant mesothelioma. The incidence and histologic types of lung carcinoma and malignant mesothelioma within the cohort were examined by review of available histopathologic material and medical records. Further, mutations of the p53 gene were analyzed whenever possible as it has previously been suggested that radon-associated lung carcinomas exhibit specific mutational patterns. The cumulative risk for lung carcinoma reached 11.0% based on 20 confirmed cases. Nine were small cell lung cancer (SCLC), whereas the expected frequency was 18%. The risk for malignant mesothelioma reached 2.5% based on 7 cases. The actuarial risk of malignant mesothelioma for patients given more than 20 ml Thorotrast was 7.8% compared to 1.4% for patients administered smaller amounts. Seven lung carcinomas and 5 malignant mesotheliomas were analyzed for p53 mutations; only 1 (in a lung adenocarcinoma) was detected. A possible association between Thorotrast and SCLC is suggested. In addition, a possible dose-response gradient exists for Thorotrast and malignant mesothelioma.

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

    PubMed Central

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

    2016-01-01

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

  9. [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.

  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. PMID:23829961

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

    PubMed

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

    2016-09-01

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

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

    PubMed

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

    2016-09-01

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

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

    PubMed

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

    2016-01-01

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

  15. Classification of human lung carcinomas by mRNA expression profiling reveals distinct adenocarcinoma subclasses.

    PubMed

    Bhattacharjee, A; Richards, W G; Staunton, J; Li, C; Monti, S; Vasa, P; Ladd, C; Beheshti, J; Bueno, R; Gillette, M; Loda, M; Weber, G; Mark, E J; Lander, E S; Wong, W; Johnson, B E; Golub, T R; Sugarbaker, D J; Meyerson, M

    2001-11-20

    We have generated a molecular taxonomy of lung carcinoma, the leading cause of cancer death in the United States and worldwide. Using oligonucleotide microarrays, we analyzed mRNA expression levels corresponding to 12,600 transcript sequences in 186 lung tumor samples, including 139 adenocarcinomas resected from the lung. Hierarchical and probabilistic clustering of expression data defined distinct subclasses of lung adenocarcinoma. Among these were tumors with high relative expression of neuroendocrine genes and of type II pneumocyte genes, respectively. Retrospective analysis revealed a less favorable outcome for the adenocarcinomas with neuroendocrine gene expression. The diagnostic potential of expression profiling is emphasized by its ability to discriminate primary lung adenocarcinomas from metastases of extra-pulmonary origin. These results suggest that integration of expression profile data with clinical parameters could aid in diagnosis of lung cancer patients. PMID:11707567

  16. 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

  17. Non-Small Cell Lung Carcinoma Biomarker Testing: The Pathologist's Perspective.

    PubMed

    Brega, Elisa; Brandao, Guilherme

    2014-01-01

    Biomarker testing has become standard of care for patients diagnosed with non-small cell lung carcinoma (NSCLC). Although, it can be successfully performed in circulating tumor cells, at present, the vast majority of investigations are carried out using direct tumor sampling, either through aspiration methods, which render most often isolated cells, or tissue sampling, that could range from minute biopsies to large resections. Consequently, pathologists play a central role in this process. Recent evidence suggests that refining NSCLC diagnosis might be clinically significant, particularly in cases of lung adenocarcinomas (ADC), which in turn, has prompted a new proposal for the histologic classification of such pulmonary neoplasms. These changes, in conjunction with the mandatory incorporation of biomarker testing in routine NSCLC tissue processing, have directly affected the pathologist's role in lung cancer work-up. This new role pathologists must play is complex and demanding, and requires a close interaction with surgeons, oncologists, radiologists, and molecular pathologists. Pathologists often find themselves as the central figure in the coordination of a process, that involves assuring that the tumor samples are properly fixed, but without disruption of the DNA structure, obtaining the proper diagnosis with a minimum of tissue waste, providing pre-analytical evaluation of tumor samples selected for biomarker testing, which includes assessment of the proportion of tumor to normal tissues, as well as cell viability, and assuring that this entire process happens in a timely fashion. Therefore, it is part of the pathologist's responsibilities to assure that the samples received in their laboratories, be processed in a manner that allows for optimal biomarker testing. This article goal is to discuss the essential role pathologists must play in NSCLC biomarker testing, as well as to provide a summarized review of the main NSCLC biomarkers of clinical interest

  18. Targeting the phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway: an emerging treatment strategy for squamous cell lung carcinoma.

    PubMed

    Beck, Joseph Thaddeus; Ismail, Amen; Tolomeo, Christina

    2014-09-01

    Squamous cell lung carcinoma accounts for approximately 30% of all non-small cell lung cancers (NSCLCs). Despite progress in the understanding of the biology of cancer, cytotoxic chemotherapy remains the standard of care for patients with squamous cell lung carcinoma, but the prognosis is generally poor. The phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway is one of the most commonly activated signaling pathways in cancer, leading to cell proliferation, survival, and differentiation. It has therefore become a major focus of clinical research. Various alterations in the PI3K/AKT/mTOR pathway have been identified in squamous cell lung carcinoma and a number of agents targeting these alterations are in clinical development for use as single agents and in combination with other targeted and conventional treatments. These include pan-PI3K inhibitors, isoform-specific PI3K inhibitors, AKT inhibitors, mTOR inhibitors, and dual PI3K/mTOR inhibitors. These agents have demonstrated antitumor activity in preclinical models of NSCLC and preliminary clinical evidence is also available for some agents. This review will discuss the role of the PI3K/AKT/mTOR pathway in cancer and how the discovery of genetic alterations in this pathway in patients with squamous cell lung carcinoma can inform the development of targeted therapies for this disease. An overview of ongoing clinical trials investigating PI3K/AKT/mTOR pathway inhibitors in squamous cell lung carcinoma will also be included.

  19. Intussusception of small intestine due to metastasis of large cell carcinoma of the lung with a rhabdoid phenotype.

    PubMed

    Otera, H; Ikeda, F; Nakagawa, S; Kono, Y; Sakurai, T; Tada, K; Hashimoto, K; Ikeda, A

    2010-09-01

    Large cell carcinoma of the lung with a rhabdoid phenotype is a rare type of lung cancer, and does not commonly metastasize to the small intestine. Herein we describe a 63-yr-old Japanese male with ileus resulting from small intestinal metastasis from lung cancer. Tumour enlargement was rapid and could not be treated with chemotherapy.

  20. 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

  1. 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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  4. Surgical excision of lung metastases from squamous carcinoma of the cervix. A report of 2 cases.

    PubMed

    de Moor, N G; Berry, A V; Nissenbaum, M M

    1983-01-01

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

  5. Sarcomatoid lung carcinomas show high levels of Programmed death Ligand-1 (PD-L1)

    PubMed Central

    Velcheti, Vamsidhar; Rimm, David L.; Schalper, Kurt A.

    2013-01-01

    Programmed death-1 (PD-1) is a co-inhibitory inducible receptor present on T-cells and macrophages. Tumor cells with increased programmed death ligand-1 (PD-L1) are believed to escape immunity through activation of PD-1/PD-L1 pathway and suppression of effector immune responses. Recent strategies targeting the PD-1/PD-L1 axis have shown promising results in patients with several tumors types, including lung carcinomas. Preliminary data suggests that PD-L1 protein expression might predictive response to such therapies. Sarcomatoid carcinomas (SCs) of the lung include rare subtypes of poorly differentiated non-small cell lung carcinomas (NSCLC) of high grade and aggressive behavior. The biology of these neoplasms is poorly understood and they frequently show increased local inflammatory and lymphocytic infiltration. Here, we report the expression of PD-L1 in 13 SCs from two large retrospective lung cancer cohorts. Using automated quantitative immunofloresence (aqIF/AQUA®) and a mouse monoclonal antibody directed against the extra-cellular domain of PD-L1, we show that 9 of 13 (69.2%) patients with SCs are positive for PD-L1 and their levels are higher than in conventional NSCLC. These results provide rationale for the potential use of targeted immunetherapy in lung SCs. PMID:23676558

  6. The Pivotal Role of IKKα in the Development of Spontaneous Lung Squamous Cell Carcinomas

    PubMed Central

    Xiao, Zouxiang; Jiang, Qun; Willette-Brown, Jami; Xi, Sichuan; Zhu, Feng; Burkett, Sandra; Back, Timothy; Song, Na-Young; Datla, Mahesh; Sun, Zhonghe; Goldszmid, Romina; Lin, Fanching; Cohoon, Travis; Pike, Kristen; Wu, Xiaolin; Schrump, David S.; Wong, Kwok-Kin; Young, Howard A.; Trinchieri, Giorgio; Wiltrout, Robert H.; Hu, Yinling

    2013-01-01

    SUMMARY Here, we report that kinase-dead IKKα knock-in mice develop spontaneous lung squamous cell carcinomas (SCCs) associated with IKKα downregulation and marked pulmonary inflammation. IKKα reduction upregulated the expression of p63, Trim29, and keratin 5 (K5), which serve as diagnostic markers for human lung SCCs. IKKαlowK5+p63hi cell expansion and SCC formation were accompanied by inflammation-associated deregulation of oncogenes, tumor suppressors, and stem cell regulators. Reintroducing transgenic K5.IKKα, depleting macrophages, and reconstituting irradiated mutant animals with WT bone marrow (BM) prevented SCC development, suggesting that BM-derived IKKα-mutant macrophages promote the transition of IKKαlowK5+p63hi cells to tumor cells. This mouse model resembles human lung SCCs, sheds light on the mechanisms underlying lung malignancy development, and identifies targets for therapy of lung SCCs. PMID:23597566

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

    ClinicalTrials.gov

    2016-06-30

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

  8. From Uniplex to Multiplex Molecular Profiling in Advanced Non-Small Cell Lung Carcinoma.

    PubMed

    Ileana, Ecaterina E; Wistuba, Ignacio I; Izzo, Julie G

    2015-01-01

    Non-small cell lung carcinoma is a leading cause of cancer death worldwide. Understanding the molecular biology of survival and proliferation of cancer cells led to a new molecular classification of lung cancer and the development of targeted therapies with promising results. With the advances of image-guided biopsy techniques, tumor samples are becoming smaller, and the molecular testing techniques have to overcome the challenge of integrating the characterization of a panel of abnormalities including gene mutations, copy-number changes, and fusions in a reduced number of assays using only a small amount of genetic material. This article reviews the current knowledge about the most frequent actionable molecular abnormalities in non-small cell lung carcinoma, the new approaches of molecular analysis, and the implications of these findings in the context of clinical practice.

  9. Gastrin releasing peptide is a selective mitogen for small cell lung carcinoma in vitro.

    PubMed Central

    Weber, S; Zuckerman, J E; Bostwick, D G; Bensch, K G; Sikic, B I; Raffin, T A

    1985-01-01

    Human small cell lung carcinoma (SCLC) cells have been shown to contain significant levels of a bombesin-immunoreactive peptide. The 27-amino acid peptide, gastrin releasing peptide (GRP), has recently been shown to be responsible for the bombesin-like immunoreactivity found in SCLC cells. Among four lung cancer cell lines examined in vitro, GRP exhibited mitogenic activity for two SCLC subtypes, but not for a squamous carcinoma or adenocarcinoma lung cell line. The mitogenicity of the GRP molecule has been isolated to the carboxyterminal fragment, designated GRP 14-27, which is in part homologous to bombesin. The aminoterminal fragment, GRP 1-16, is no homologous to bombesin and exhibits no mitogenic activity. Thus, GRP may be an important growth regulating or autocrine factor in human SCLC. PMID:2981251

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

    PubMed Central

    2014-01-01

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

  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. “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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2016-01-01

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

  15. 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

  16. True 3q Chromosomal Amplification in Squamous Cell Lung Carcinoma by FISH and aCGH Molecular Analysis: Impact on Targeted Drugs

    PubMed Central

    Brunelli, Matteo; Bria, Emilio; Nottegar, Alessia; Cingarlini, Sara; Simionato, Francesca; Caliò, Anna; Eccher, Albino; Parolini, Claudia; Iannucci, Antonio; Gilioli, Eliana; Pedron, Serena; Massari, Francesco; Tortora, Giampaolo; Borze, Ioana; Knuutila, Sakari; Gobbo, Stefano; Santo, Antonio; Tondulli, Luca; Calabrò, Francesco; Martignoni, Guido; Chilosi, Marco

    2012-01-01

    Squamous lung carcinoma lacks specific “ad hoc” therapies. Amplification of chromosome 3q is the most common genomic aberration and this region harbours genes having role as novel targets for therapeutics. There is no standard definition on how to score and report 3q amplification. False versus true 3q chromosomal amplification in squamous cell lung carcinoma may have tremendous impact on trials involving drugs which target DNA zones mapping on 3q. Forty squamous lung carcinomas were analyzed by FISH to assess chromosome 3q amplification. aCGH was performed as gold-standard to avoid false positive amplifications. Three clustered patterns of fluorescent signals were observed. Eight cases out of 40 (20%) showed ≥8 3q signals. Twenty out of 40 (50%) showed from 3 to 7 signals. The remaining showed two fluorescent signals (30%). When corrected by whole chromosome 3 signals, only cases with ≥8 signals maintained a LSI 3q/CEP3 ratio >2. Only the cases showing 3q amplification by aCGH (+3q25.3−3q27.3) showed ≥8 fluorescent signals at FISH evidencing a 3q/3 ratio >2. The remaining cases showed flat genomic portrait at aCGH on chromosome 3. We concluded that: 1) absolute copy number of 3q chromosomal region may harbour false positive interpretation of 3q amplification in squamous cell carcinoma; 2) a case results truly “amplified for chromosome 3q” when showing ≥8 fluorescent 3q signals; 3) trials involving drugs targeting loci on chromosome 3q in squamous lung carcinoma therapy have to consider false versus true 3q chromosomal amplification. PMID:23236352

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

    PubMed Central

    2014-01-01

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

  18. 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.

  19. 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.

  20. Unusual case of cavitary lung metastasis from squamous cell carcinoma of the uterine cervix.

    PubMed

    Raissouni, Soundouss; Ghizlane, Rais; Mouzount, Houda; Saoussane, Kharmoum; Khadija, Setti; Zouaidia, Fouad; Latib, Rachida; Mrabti, Hind; Errihani, Hassan

    2013-01-01

    Spontaneous excavation of primary lung cancer is common; however cavitation of metastatic lung lesions is rare and usually confused with benign lesions. In Moroccan context tuberculosis is the first suspected diagnosis of lung excavations. We report a rare case of cavitary lung metastasis of a uterine cervix cancer, treated initially as tuberculosis. A 40-year old non-smoking woman with a known history of squamous cell carcinoma of the uterine cervix since August 2005; presented on September 2008 with right chest pain without fever, hemoptysis or weight loss. CT scan showed a thin walled cavity. Empirical Antibiotic therapy was conducted 15 days with poor outcome. Then antibacillary treatment was started with no proof of mycobacterial infection. A month later, the patient presented with gynecological bleeding and a pneumothorax. Bronchoscopy with transbronchial biopsy of the cavitary mass was performed. Pathology demonstrated a metastatic squamous cell carcinoma. Pelvic examination and MRI showed a subsequent local cervix recurrence. Patient underwent 3 courses of systemic chemotherapy. She died on June 2009 due to progressive disease. Even cavitary lung metastases are rare and benign differential diagnosis are more common, clinician should be careful in neoplastic context and investigation should be done to eliminate a recurrence. PMID:23560120

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

    PubMed

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

    2006-06-01

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

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

    PubMed

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

    2012-07-01

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

  3. SIAH2 antagonizes TYK2-STAT3 signaling in lung carcinoma cells.

    PubMed

    Müller, Sylvia; Chen, Yuan; Ginter, Torsten; Schäfer, Claudia; Buchwald, Marc; Schmitz, Lienhard M; Klitzsch, Jana; Schütz, Alexander; Haitel, Andrea; Schmid, Katharina; Moriggl, Richard; Kenner, Lukas; Friedrich, Karlheinz; Haan, Claude; Petersen, Iver; Heinzel, Thorsten; Krämer, Oliver H

    2014-05-30

    The Janus tyrosine kinases JAK1-3 and tyrosine kinase-2 (TYK2) are frequently hyperactivated in tumors. In lung cancers JAK1 and JAK2 induce oncogenic signaling through STAT3. A putative role of TYK2 in these tumors has not been reported. Here, we show a previously not recognized TYK2-STAT3 signaling node in lung cancer cells. We reveal that the E3 ubiquitin ligase seven-in-absentia-2 (SIAH2) accelerates the proteasomal degradation of TYK2. This mechanism consequently suppresses the activation of STAT3. In agreement with these data the analysis of primary non-small-cell lung cancer (NSCLC) samples from three patient cohorts revealed that compared to lung adenocarcinoma (ADC), lung squamous cell carcinoma (SCC) show significantly higher levels of SIAH2 and reduced STAT3 phosphorylation levels. Thus, SIAH2 is a novel molecular marker for SCC. We further demonstrate that an activation of the oncologically relevant transcription factor p53 in lung cancer cells induces SIAH2, depletes TYK2, and abrogates the tyrosine phosphorylation of STAT1 and STAT3. This mechanism appears to be different from the inhibition of phosphorylated JAKs through the suppressor of cytokine signaling (SOCS) proteins. Our study may help to identify molecular mechanisms affecting lung carcinogenesis and potential therapeutic targets. PMID:24833526

  4. 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

  5. Products of vasopressin gene expression in small-cell carcinoma of the lung.

    PubMed Central

    Friedmann, A. S.; Malott, K. A.; Memoli, V. A.; Pai, S. I.; Yu, X. M.; North, W. G.

    1994-01-01

    Small-cell neuroendocrine carcinoma of the lung is known to express products related to the vasopressin gene, although these products have been reported to sometimes differ from those generated by neurones of the hypothalamo-neurohypophyseal system. To further investigate vasopressin gene expression in neuroendocrine carcinomas, we performed immunohistochemistry on 24 histologically classified small-cell carcinomas using antibodies directed against different regions of the vasopressin precursor. All of the tumours examined contained at least two parts of the vasopressin precursor, suggesting that vasopressin might have a biological role in these tumours and indicating a role for these products in tumour diagnosis and treatment. Sixty-seven per cent of the tumours contained immunoreactivity for all major regions of the precursor: vasopressin, vasopressin-associated human neurophysin, the bridging region between the hormone and the neurophysin, and vasopressin-associated human glycopeptide. However, 33% of the tumours examined appeared to express only part of the vasopressin precursor, as evidenced by the absence of immunoreactivity for the neurophysin and/or the glycopeptide. These results support the proposition that both normal and abnormal vasopressin gene expression occurs in small-cell carcinoma of the lung. Images Figure 1 Figure 2 Figure 3 PMID:8297723

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    PubMed

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

    2016-01-01

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

  8. [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.

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. Are there radiographic, metabolic, and prognostic differences between cavitary and noncavitary nonsmall cell lung carcinoma? A retrospective fluorodeoxyglucose positron emission tomography/computed tomography study

    PubMed Central

    Nguyen, Nghi C.; Abhishek, Kumar; Nyon, Samuel; Farghaly, Hussein Rabie S.; Osman, Medhat M.; Reimers, Hans-Joachim

    2016-01-01

    AIMS: The prognosis of nonsmall cell lung cancer with cavitation (NSCLC-c) is not well-known. We compared the positron emission tomography/computed tomography (PET/CT) findings and survival data of patients with NSCLC-c patients with those without cavitation (NSCLC-nc). METHODS: Between 7/2004 and 6/2007, cavitary lung lesions were identified in 46/248 patients undergoing fluorodeoxyglucose (FDG) PET/CT for lung nodule characterization or lung cancer staging. Within the same period, 40 of 202 patients with NSCLC-nc were randomly selected for comparison. The primary was assessed by location, size, cell type, and standardized uptake value (SUV). Disease stage was determined according to American Joint Committee on Cancer guidelines for lung cancer. Kaplan–Meier method was used for survival analysis and Cox regression to assess the effect of clinical and imaging variables on survival. RESULTS: NSCLC-c was found in 87% of patients that had a cavitary lung lesion at PET/CT. Squamous cell carcinoma, primary size and primary-to-liver SUV ratio differed significantly between NSCLC-c and NSCLC-nc, whereas age, gender, primary location, primary SUV, type of treatment, and disease stage did not. Median survival and overall 5-year survival were 19 months and 24% for NSCLC-c, and 31 months and 31% for NSCLC-nc, P = 0.23. Disease stage was the only predictor of survival. CONCLUSION: Cavitary lung lesions in patients undergoing FDG PET/CT harbor a significant risk for cancer. NSCLC-c is associated with squamous cell carcinoma, larger size, and greater FDG metabolism compared with NSCLC-nc, although these variables may not be predictive of survival. Nonetheless, PET/CT contributes to accurate staging and has an indirect impact on prognosis. PMID:26933457

  15. 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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    2012-01-01

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

  18. Human papillomavirus infection in lung vs. oral squamous cell carcinomas: a polymerase chain reaction study.

    PubMed

    Halimi, M; Morshedi Asl, S

    2011-06-01

    The role of Human Papillomavirus (HPV) has been suspected in pathogenesis of various malignancies; however, the available data are not conclusive. This study aimed to determine and compare the frequency of HPV infection in oral and lung Squamous Cell Carcinoma (SCC) by a sensitive method. Sixty specimens of oral and lung SCC (30 cases each one) were reevaluated in Tabriz Imam Reza Centre in a 24 month period. Following genomic DNA extract, the Polymerase Chain Reaction (PCR) amplification was performed in presence of specific MY11 and MY09 primers for HPV infection. Three cervical specimens and a combination of PCR solution lacking DNA plus healthy persons' DNA samples were employed as positive and negative controls, respectively. The oral group was significantly older than the lung group (68.90 vs. 56.67 y, p < 0.001) with more males in the latter (83.3 vs. 60%; p = 0.04). Percentages of HPV infection in the oral and lung groups were comparable (20 vs. 10%, respectively; p = 0.47). Majority of patients with HPV infection were older than 60 years (88.9%) or male (88.9%). In the oral group, all these cases were well differentiated and the majority was of lower lip origin (83.3%). In the lung group, 66.7% of these specimens were moderately differentiated and the origin was bronchus in all cases. In conclusion, the rate of HPV infection in lung and oral SCC samples is rather lower than the previous reports in the literature. This rate is apparently higher in the oral than the lung SCC specimens. PMID:22235505

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

    PubMed

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

    2016-01-01

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

  20. Palmar fasciitis and polyarthritis syndrome associated with non-small-cell lung carcinoma.

    PubMed

    Sheehy, Claire; Ryan, John G; Kelly, Michael; Barry, Maurice

    2007-11-01

    A 56-year-old man presented with pain and stiffness in both shoulders and developed severe, rapidly progressive contractures of the fingers. Examination revealed subcutaneous thickening in both palms with fixed flexion deformities of all digits except the thumbs. Initial investigations including a malignancy screen were all normal/negative. Eighteen months later, he was diagnosed with metastatic non-small-cell lung carcinoma. Although rare, palmar fasciitis and polyarthritis syndrome is an important paraneoplastic syndrome for rheumatologists to be aware of, as the musculoskeletal symptoms may precede neoplastic manifestations by many months and may improve with appropriate treatment.

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

    PubMed Central

    Rizk, Norman W.

    1985-01-01

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

  2. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2012-08-01

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

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

    ClinicalTrials.gov

    2016-10-24

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

  5. Autocrine epiregulin activates EGFR pathway for lung metastasis via EMT in salivary adenoid cystic carcinoma

    PubMed Central

    Xu, Dongliang; Liao, Yueling; Zhang, Ling; Liu, Liu; Yu, Wenwen; Wang, Yanan; He, Yue; Hu, Jingzhou; Guo, Wenzheng; Wang, Tong; Sun, Beibei; Song, Hongyong; Yin, Huijing; Liu, Jingyi; Wu, Yadi; Zhu, Hanguang; Zhou, Binhua P.; Deng, Jiong; Zhang, Zhiyuan

    2016-01-01

    Salivary adenoid cystic carcinoma (SACC) is characterized by invasive local growth and a high incidence of lung metastasis. Patients with lung metastasis have a poor prognosis. Treatment of metastatic SACC has been unsuccessful, largely due to a lack of specific targets for the metastatic cells. In this study, we showed that epidermal growth factor receptors (EGFR) were constitutively activated in metastatic lung subtypes of SACC cells, and that this activation was induced by autocrine expression of epiregulin (EREG), a ligand of EGFR. Autocrine EREG expression was increased in metastatic SACC-LM cells compared to that in non-metastatic parental SACC cells. Importantly, EREG-neutralizing antibody, but not normal IgG, blocked the autocrine EREG-induced EGFR phosphorylation and the migration of SACC cells, suggesting that EREG-induced EGFR activation is essential for induction of cell migration and invasion by SACC cells. Moreover, EREG-activated EGFR stabilized Snail and Slug, which promoted EMT and metastatic features in SACC cells. Of note, targeting EGFR with inhibitors significantly suppressed both the motility of SACC cells in vitro and lung metastasis in vivo. Finally, elevated EREG expression showed a strong correlation with poor prognosis in head and neck cancer. Thus, targeting the EREG-EGFR-Snail/Slug axis represents a novel strategy for the treatment of metastatic SACC even no genetic EGFR mutation. PMID:26958807

  6. Growth characteristics and drug responses of a murine lung carcinoma in vitro and in vivo.

    PubMed

    Kaneko, T; LePage, G A

    1978-07-01

    Cells obtained from the Nettesheim lung carcinoma of DBA/2 mice, a heterogenous population grown s.c., were cultured as monolayers. These cells were serially subcultured and cloned twice, and a clone was selected for further study. This clone produced malignant tumors at the injected site when injected s.c. into male DBA/2 or C57BL/L x DBA/2 F1 mice. Referred as KLN205, this cell line had the highest rate of lung colony formation on i.v. injection. It was subcultured for over 15 generations, and its cytological characteristics were investigated. The s.c. and lung colony growth were examined histologically. The effects of treatment with two antimetabolite drugs, arabinosyl-6-mercaptopurine (NSC 406021) and 6-selenoguanosine (NSC 137679) were determined in culture and in vivo. The former was relatively ineffective; the latter was very effective both in vivo and in vitro. Several drugs used clinically for the treatment of lung cancer were also tested. This established and characterized cell line is proposed as a potential model for testing other chemotherapeutic treatments.

  7. Identification of reference genes for qRT-PCR in human lung squamous-cell carcinoma by RNA-Seq.

    PubMed

    Zhan, Cheng; Zhang, Yongxing; Ma, Jun; Wang, Lin; Jiang, Wei; Shi, Yu; Wang, Qun

    2014-04-01

    Although the accuracy of quantitative real-time polymerase chain reaction (qRT-PCR) is highly dependent on the reliable reference genes, many commonly used reference genes are not stably expressed and as such are not suitable for quantification and normalization of qRT-PCR data. The aim of this study was to identify novel reliable reference genes in lung squamous-cell carcinoma. We used RNA sequencing (RNA-Seq) to survey the whole genome expression in 5 lung normal samples and 44 lung squamous-cell carcinoma samples. We evaluated the expression profiles of 15 commonly used reference genes and identified five additional candidate reference genes. To validate the RNA-Seq dataset, we used qRT-PCR to verify the expression levels of these 20 genes in a separate set of 100 pairs of normal lung tissue and lung squamous-cell carcinoma samples, and then analyzed these results using geNorm and NormFinder. With respect to 14 of the 15 common reference genes (B2M, GAPDH, GUSB, HMBS, HPRT1, IPO8, PGK1, POLR2A, PPIA, RPLP0, TBP, TFRC, UBC, and YWHAZ), the expression levels were either too low to be easily detected, or exhibited a high degree of variability either between lung normal and squamous-cell carcinoma samples, or even among samples of the same tissue type. In contrast, 1 of the 15 common reference genes (ACTB) and the 5 additional candidate reference genes (EEF1A1, FAU, RPS9, RPS11, and RPS14) were stably and constitutively expressed at high levels in all the samples tested. ACTB, EEF1A1, FAU, RPS9, RPS11, and RPS14 are ideal reference genes for qRT-PCR analysis of lung squamous-cell carcinoma, while 14 commonly used qRT-PCR reference genes are less appropriate in this context.

  8. 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

  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. Combined Aortic Resection and Stent Graft Insertion for Local Recurrence of Metastatic Lung Carcinoma Following Stereotactic Radiotherapy: A Case Report

    PubMed Central

    Matsutani, Noriyuki; Imazuru, Tomohiro; Morita, Shigeki; Takahashi, Yusuke; Shimokawa, Tomoki; Kawamura, Masafumi

    2015-01-01

    Stereotactic radiotherapy (SRT) is a useful treatment for malignant ling tumors. However, SRT is associated with complications such as high local recurrence rate and radiation-induced lung injury. Herein, we report a case of combined aortic resection for after SRT. An 82-year-old man underwent SRT for the metastatic lung carcinoma of rectal cancer at left lower lobe. Three years later, chest computed tomography showed local recurrence at the site of radiotherapy, with suspected invasion of the descending aorta. Thoracotomy was performed after metastatic lung carcinoma interpolation of a stent graft in the descending aorta. Because the tumor firmly adhered to the aorta, left lower lung lobe and aortic wall resection was performed. Pathological findings revealed fibrous hypertrophy and adhesion between the visceral pleura and aorta. As shown in our case, combined aortic resection and stent graft insertion is an effective minimally invasive and safe treatment for SRT-induced tissue damage. PMID:26256818

  11. 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.

  12. 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.

  13. Cancer procoagulant (CP) in lung cancer.

    PubMed

    Rucińska, M; Skrzydlewski, Z; Zaremba, E; Furman, M; Kasacka, I

    1997-01-01

    Lung cancers (squamous cell carcinoma, microcellular carcinoma, macrocellular carcinoma and adenocarcinoma) show procoagulant activity. It mainly depends on the presence of cancer procoagulant (CP) in lung cancer cells.

  14. Detection of human papillomavirus in non-small cell carcinoma of the lung.

    PubMed

    Chang, Sing Yun; Keeney, Michael; Law, Mark; Donovan, Janis; Aubry, Marie-Christine; Garcia, Joaquin

    2015-11-01

    High-risk human papillomavirus (hrHPV) is an etiologic agent in squamous cell carcinoma (SqCC) arising in the oropharynx and cervix, and a proven prognostic factor in oropharyngeal SqCC. Many studies have found HPV in non-small cell lung carcinoma (NSCLC). Recent studies advocate the detection of messenger RNA transcripts of E6/E7 as more reliable evidence of transcriptively active HPV in tumor cells. The clinical significance of finding HPV remains unclear in NSCLC. This study sought to determine the prevalence of biologically active HPV infection in NSCLC comparing different methodologies. Surgical pathology material from resected primary lung adenocarcinoma (ADC; n=100) and SqCC (n=96) were retrieved to construct tissue microarrays. In situ hybridization (ISH) for hrHPV DNA (DNA-ISH), hrHPV E6/E7 RNA (RNA-ISH), and p16 immunohistochemistry were performed. Cases of oropharyngeal SqCC with known HPV infection were used as positive controls. Expression of p16 was scored as positive if at least 70% of tumor cells showed diffuse and strong nuclear and cytoplasmic staining. Punctate nuclear hybridization signals by DNA-ISH in the malignant cells defined an HPV-positive carcinoma. Of the 196 patients (range, 33-87 years; 108 men), p16 was positive in 19 ADCs and 9 SqCCs, but HPV DNA-ISH and RNA-ISH were negative in all cases. Our study did not detect HPV infection by DNA-ISH or RNA-ISH in any cases of primary NSCLC despite positive p16 expression in a portion of ADC and SqCC. p16 should therefore not be used as a surrogate marker for HPV infection in NSCLC.

  15. 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.

  16. 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. PMID:26372838

  17. 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.

  18. Molecular alterations in non-small cell lung carcinomas of the young.

    PubMed

    VandenBussche, Christopher J; Illei, Peter B; Lin, Ming-Tseh; Ettinger, David S; Maleki, Zahra

    2014-12-01

    Lung cancer is the leading cause of cancer death in the United States. Gene alterations are significant in lung tumorigenesis, with certain genes (Kristen rat sarcoma viral oncogene homolog (KRAS), epidermal growth factor receptor [EGFR], anaplastic lymphoma kinase [ALK], and B-Raf proto-oncogene, serine/threonine kinase (BRAF)) possessing alterations important in the prognosis and treatment of lung adenocarcinoma. Mutation frequencies are affected by different patient factors, such as smoking history, age, and race. Because most lung cancers occur in patients older than age of 50 years, few studies have examined molecular alterations present in these younger patients. The pathology database was searched for patients age of 50 years or younger with non-small cell lung carcinomas (NSCLCs) tested for EGFR, ALK, KRAS, and/or BRAF alterations. A total of 53 cases were identified. The mean patient age was 44.4 years old, and there were 19 men and 34 women. Of the tumors, 11.6% had ALK rearrangements, 25.5% had KRAS mutations, and 20.0% had EGFR mutations. No BRAF mutations were identified in the 28 cases tested. All but 1 (92% [12/13]) tumor with KRAS mutation were from women patients. A smoking history of greater than 5 pack-years was associated with KRAS mutations and negatively associated with EGFR mutations and ALK translocation. The frequencies of EGFR mutation and ALK translocation in the study cohort are greater than the reported frequencies among NSCLC from adults of all ages in the United States but less than the reported frequencies among NSCLC from East Asian young adults. The frequency of KRAS mutation is significantly greater than what was previously found in young Japanese patients.

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

    PubMed Central

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

    2014-01-01

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

  20. Thallium-201-chloride and technetium-99m-MIBI SPECT of primary and metastatic lung carcinoma.

    PubMed

    Kashitani, N; Makihara, S; Maeda, T; Eda, R; Takeyama, H; Hiraki, Y

    1999-01-01

    We compared technetium-99m-MIBI (Tc-99m MIBI) with thallium-201-chloride (Tl-201) SPECT imaging in patients with lung carcinoma. In addition, we compared the imaging characteristics of Tl-201 and Tc-99m MIBI after radiation therapy. Thirty-seven patients with primary lung carcinoma were evaluated with SPECT imaging for metastasis to the mediastinal lymph nodes and brain. Patients were imaged with Tl-201 chloride images 10 and 180 min after injection. Patients were also imaged 10 min after injection of Tc-99m MIBI. The sensitivity of Tl-201 SPECT for the primary lesion and brain metastasis was 97.1% and 70.0% respectively at 10 min and 97.1% and 60.0% at 180 min. The sensitivity of Tc-99m MIBI SPECT was 97.1% (for the identification of the primary lesion) and 50.0% (for the detection of brain metastasis) at 10 min. The uptake ratios (count in tumor/count in normal lung or brain) at 10 min on the Tl-201 SPECT and on the Tc-99m MIBI SPECT were not significantly different for the primary tumor or for brain metastasis. The uptake ratios were better for Tc-99m MIBI than for Tl-201 [2.82 vs. 1.99 (p<0.05)] for mediastinal lymph nodes. Decreasing uptake ratios and retention index with both agents after radiation therapy are concordant to the follow-up clinical course. Tc-99m MIBI SPECT is more sensitive in the detection of metastasis to mediastinal lymph nodes than Tl-201 SPECT.

  1. 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

  2. Extrauterine epithelioid trophoblastic tumors presenting as primary lung carcinomas: morphologic and immunohistochemical features to resolve a diagnostic dilemma.

    PubMed

    Lewin, Sharyn N; Aghajanian, Carol; Moreira, Andre L; Soslow, Robert A

    2009-12-01

    Our objective was to describe the clinicopathologic features of epithelioid trophoblastic tumors (ETTs) in a series of patients who presented with elevated beta-human chorionic gonadotrophin (hCG) levels and extrauterine lesions resembling primary lung carcinomas. Clinical and pathologic materials were reviewed and Shih and Kurman's diagnostic criteria were applied. Three parous women (38, 49, and 34 y of age) with elevated beta-hCG levels had nondiagnostic gynecologic evaluations, including negative dilation and curettage specimens. Imaging revealed isolated pulmonary lesions, 2 to 8.5 cm in size, resembling primary lung carcinomas. Two patients received multiagent chemotherapy consisting of etoposide, methotrexate, dactinomycin, alternating with cisplatin and etoposide, and all underwent pulmonary resection. Histologically, the cytologic features, epithelioid growth pattern, and hyaline-like material simulated the appearance of nonsmall cell lung carcinoma, but overall, the histologic features along with the immunophenotype supported classification as ETT. Follow-up hysterectomy specimens were histologically normal. All 3 patients are alive and well. The rarity of ETT and its resemblance to squamous and pleomorphic carcinomas of lung have led to diagnostic difficulties. When reproductive-age women present with elevated beta-hCG levels, a pulmonary lesion, and no apparent intrauterine disease, primary pulmonary ETT should be considered. Correlating clinical indices with specific morphologic and immunohistochemical features can ensure diagnostic accuracy and appropriate treatment for favorable outcomes.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-05-01

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

  6. Non-small-cell lung carcinoma tumor growth without morphological evidence of neo-angiogenesis.

    PubMed Central

    Pezzella, F.; Pastorino, U.; Tagliabue, E.; Andreola, S.; Sozzi, G.; Gasparini, G.; Menard, S.; Gatter, K. C.; Harris, A. L.; Fox, S.; Buyse, M.; Pilotti, S.; Pierotti, M.; Rilke, F.

    1997-01-01

    Neoplastic growth is usually dependent on blood supply, and it is commonly accepted that this is provided by the formation of new vessels. However, tumors may be able to grow without neovascularization if they find a suitable vascular bed available. We have investigated the pattern of vascularization in a series of 500 primary stage I non-small-cell lung carcinomas. Immunostaining of endothelial cells has highlighted four distinct patterns of vascularization. Three patterns (which we called basal, papillary, and diffuse) have in common the destruction of normal lung and the production of newly formed vessels and stroma. The fourth pattern, which we called alveolar or putative nonangiogenic, was observed in 16% (80/500) of the cases and is characterized by lack of parenchymal destruction and absence of both tumor associated stroma and new vessels. The only vessels present were the ones in the alveolar septa, and their presence highlighted, through the whole tumor, the lung alveoli filled up by the neoplastic cells. This observation suggests that, if an appropriate vascular bed is available, a tumor can exploit it and grows without inducing neo-angiogenesis. This could have implications for strategies aimed at inhibiting tumor growth by vascular targeting or inhibition of angiogenesis. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:9358768

  7. Non-small-cell lung carcinoma tumor growth without morphological evidence of neo-angiogenesis.

    PubMed

    Pezzella, F; Pastorino, U; Tagliabue, E; Andreola, S; Sozzi, G; Gasparini, G; Menard, S; Gatter, K C; Harris, A L; Fox, S; Buyse, M; Pilotti, S; Pierotti, M; Rilke, F

    1997-11-01

    Neoplastic growth is usually dependent on blood supply, and it is commonly accepted that this is provided by the formation of new vessels. However, tumors may be able to grow without neovascularization if they find a suitable vascular bed available. We have investigated the pattern of vascularization in a series of 500 primary stage I non-small-cell lung carcinomas. Immunostaining of endothelial cells has highlighted four distinct patterns of vascularization. Three patterns (which we called basal, papillary, and diffuse) have in common the destruction of normal lung and the production of newly formed vessels and stroma. The fourth pattern, which we called alveolar or putative nonangiogenic, was observed in 16% (80/500) of the cases and is characterized by lack of parenchymal destruction and absence of both tumor associated stroma and new vessels. The only vessels present were the ones in the alveolar septa, and their presence highlighted, through the whole tumor, the lung alveoli filled up by the neoplastic cells. This observation suggests that, if an appropriate vascular bed is available, a tumor can exploit it and grows without inducing neo-angiogenesis. This could have implications for strategies aimed at inhibiting tumor growth by vascular targeting or inhibition of angiogenesis.

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

    PubMed

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

    2013-01-01

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

  9. The multifocality of bronchioloalveolar lung carcinoma: evidence and implications of a multiclonal origin.

    PubMed

    Barsky, S H; Grossman, D A; Ho, J; Holmes, E C

    1994-08-01

    Bronchioloalveolar lung carcinoma (BAC) is a unique type of lung cancer with distinguishing pathologic, biologic, epidemiologic, and perhaps etiologic features that set it apart from all other forms of lung cancer, including general adenocarcinoma, into which it is traditionally grouped. Recent studies at our institution have demonstrated a near exponential increase in BAC cases with 25% showing evidence of multifocality. Although some theories suggest that this multifocality is caused by intrapulmonary aerosol/aspiration or lymphatic spread, this study provides evidence for multiclonality as the basis for some cases of multifocal BAC by exploiting a novel strategy for clonality determinations that involves polymerase chain reaction amplification of a 511-base pair region located within the first intron of the human hypoxanthine phosphoribosyltransferase gene, a site that contains inactive X chromosomal obligately methylated HpaII/MspI sites and single-base allelic polymorphisms in 5 to 10% of females. BAC cells, obtained by enzymatic dissociation of different fresh/paraffin-embedded tumoral foci from polymorphic individuals with multilobar or bilateral BAC, were sorted to homogeneity with a fluorescein-conjugated anticarcinoembryonic antigen and then subjected to genomic DNA extraction and HpaII digestion before polymerase chain reaction amplification and subsequent analysis of the product on denaturing gradient gel electrophoresis. The differing migrations of the single homoduplexes generated were indicative of BAC clonal nonidentity or multiclonality in three separate cases. The demonstration of multiclonality in some cases of BAC provides an alternate explanation for multifocality. PMID:7527541

  10. Frequent loss of Fas expression and function in human lung tumours with overexpression of FasL in small cell lung carcinoma.

    PubMed

    Viard-Leveugle, Isabelle; Veyrenc, Sylvie; French, Lars E; Brambilla, Christian; Brambilla, Elisabeth

    2003-10-01

    Fas (CD95) and its ligand FasL signal apoptosis and are involved in tissue homeostasis and the elimination of target cells by cytotoxic T cells. Corruption of this signalling pathway in tumour cells, for example by reduced Fas expression or increased FasL expression, can participate in tumour development and immune escape. The present study has analysed Fas/FasL expression and Fas death signalling function in vivo in lung tumour tissues [57 non-small cell lung carcinomas and 64 neuroendocrine lung tumours including small cell lung carcinoma (SCLC)] in comparison with normal lung tissue, and in vitro in neuroendocrine tumour cell lines in comparison with normal human bronchial epithelial cells. The Fas expression score was markedly decreased compared with normal lung tissue in 90% of the 121 lung tumours and was completely lost in 24%. The Fas staining pattern suggested cytoplasmic Fas expression in tumours, whereas membrane expression was observed in normal lung tissue. Loss of Fas at the cell surface was also shown in vitro by FACS analysis of neuroendocrine tumour cell lines and was concomitant with the resistance of tumour cells to FasL-mediated apoptosis according to in vitro cell viability. The lack of cell surface Fas expression in tumour cell lines resulted from the lack of intracellular Fas protein due to impaired Fas gene transcription. The FasL expression score was also decreased in most non-small cell lung carcinomas compared with normal bronchial cells, whereas 91% of SCLCs had higher expression than normal cells. FasL overexpression was related to advanced tumour stage as well as to a Fas/FasL ratio less than 1. It is concluded that a marked decrease in Fas expression may be part of lung tumourigenesis allowing tumour cells to escape from apoptosis. FasL overexpression in the context of Fas down-regulation in SCLC predicts the ability of SCLC cells to induce paracrine killing of Fas-expressing cytotoxic T cells. In lung tumours, Fas restoration may

  11. 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.

  12. 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

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

    PubMed

    Wu, Huiling; Wang, Wenbing; Xu, Huaxi

    2014-01-01

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

  14. 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.

  15. 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.

  16. 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

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

    PubMed

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

    1998-01-01

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

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

    PubMed

    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.

  19. 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.

  20. 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

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

    PubMed

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

    2016-03-01

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

  2. Implementing amplicon-based next generation sequencing in the diagnosis of small cell lung carcinoma metastases.

    PubMed

    Meder, Lydia; König, Katharina; Fassunke, Jana; Ozretić, Luka; Wolf, Jürgen; Merkelbach-Bruse, Sabine; Heukamp, Lukas C; Buettner, Reinhard

    2015-12-01

    Small cell lung carcinoma (SCLC) is the most aggressive entity of lung cancer. Rapid cancer progression and early formation of systemic metastases drive the deadly outcome of SCLC. Recent advances in identifying oncogenes by cancer whole genome sequencing improved the understanding of SCLC carcinogenesis. However, tumor material is often limited in the clinic. Thus, it is a compulsive issue to improve SCLC diagnostics by combining established immunohistochemistry and next generation sequencing. We implemented amplicon-based next generation deep sequencing in our routine diagnostics pipeline to analyze RB1, TP53, EP300 and CREBBP, frequently mutated in SCLC. Thereby, our pipeline combined routine SCLC histology and identification of somatic mutations. We comprehensively analyzed fifty randomly collected SCLC metastases isolated from trachea and lymph nodes in comparison to specimens derived from primary SCLC. SCLC lymph node metastases showed enhanced proliferation and frequently a collapsed keratin cytoskeleton compared to SCLC metastases isolated from trachea. We identified characteristic synchronous mutations in RB1 and TP53 and non-synchronous CREBBP and EP300 mutations. Our data showed the benefit of implementing deep sequencing into routine diagnostics. We here identify oncogenic drivers and simultaneously gain further insights into SCLC tumor biology.

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

    PubMed

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

    2016-03-01

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

  4. Telomere length and telomerase expression in atypical adenomatous hyperplasia and small bronchioloalveolar carcinoma of the lung.

    PubMed

    Kawai, Toshiaki; Hiroi, Sadayuki; Nakanishi, Kuniaki; Meeker, Alan K

    2007-02-01

    Telomeres are located at the ends of every human chromosome and are subject to shortening at each cycle of cell division in cell senescence and early carcinogenesis. We examined the expression of telomeric DNA in 21 atypical adenomatous hyperplasias (AAHs) and 40 bronchioloalveolar carcinomas (BACs) measuring 2 cm or less in greatest diameter using fluorescent in situ hybridization and the expression of human telomerase reverse transcriptase (hTERT) messenger RNA (mRNA) in 35 AAHs and 37 BACs. The mean numbers of telomeric signals per nucleus were 5.0 in AAH and 7.4 in BAC, each significantly less than for normal cells (14.7; P < .0001), but the mean number of telomeric signals for AAH and BAC was not statistically different (P = .22). In "benign" lung samples, the pattern of expression of hTERT mRNA was barely detected in the nonciliated cells of the bronchioles and alveolar type II cells. Positive expression of hTERT mRNA was recognized in 66% of AAHs and 97% of BACs. Our results demonstrate telomere shortening, indicating its presence in the earliest phase of pulmonary carcinogenesis. Telomere length and telomerase may be involved in carcinogenesis in the lung.

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

    PubMed Central

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

    2015-01-01

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

  6. Brain metastasis from a lung mucoepidermoid carcinoma mimicking a brain abscess

    PubMed Central

    Saito, Taiichi; Ujiie, Hiroshi; Kadoyama, Shigeru; Higa, Takashi; Shiono, Saori; Teramoto, Akira

    2015-01-01

    Background: Mucoepidermoid carcinoma (MEC) is a rare tumor of the lung that accounts for 0.1–0.2% of all pulmonary tumors. To the best of our knowledge, brain metastasis from lung MEC is rare and magnetic resonance imaging (MRI) findings of this lesion have not been documented. Case Description: We herein report the case of a 72-year-old male. MRI revealed a left parietal tumor showing ring enhancement with medium gadolinium contrast and an evident high intensity area in the nonenhanced central portion on diffusion-weighted images (DWI) mimicking a brain abscess. Histologically, MEC is composed of a mixture of different cell types including mucin-secreting glandular cells and squamous cells. Accordingly, we suggest that the high DWI signal can be explained by the development of intracellular and intraluminal mucin, which have a high viscosity. Conclusion: Further accumulation of cases with brain metastasis from MEC is needed to establish the characteristic image findings, which would lead to prompt and adequate treatment. PMID:26167374

  7. 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

    2016-10-26

    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

  8. 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

  9. 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.

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

    PubMed

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

    2008-12-01

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

  11. Cytotoxic murine monoclonal antibody LAM8 with specificity for human small cell carcinoma of the lung.

    PubMed

    Stahel, R A; O'Hara, C J; Mabry, M; Waibel, R; Sabbath, K; Speak, J A; Bernal, S D

    1986-04-01

    The reactivity of the murine immunoglobulin monoclonal antibody LAM8 directed against a membrane antigen of human small cell carcinoma (SCC) of the lung was investigated on human cell lines and tissues. Indirect immunofluorescence staining, radioimmunoassays, and cytotoxicity assays showed LAM8 antibody to selectively react with SCC but not with non-SCC lung cancer cell lines and extrapulmonary tumor cell lines. Unlike other SCC antibodies, including those we have previously described, highly preferential reactivity with SCC tissues was also demonstrated by immunoperoxidase staining of deparaffinized formalin-fixed tissue sections. Membrane and cytoplasmic staining was seen in of 9 of 12 SCC tissues. No significant staining was seen in non-SCC lung cancer and a wide range of other tumors, including mesothelioma and bronchial carcinoids. Significant LAM8 reactivity was also absent in normal tissues of all major organs. Few tumors and epithelial tissues, including bronchial epithelium had rare LAM8 positive cells which were always less than 2% of the entire cell population. In vitro treatment with antibody and human complement was highly cytotoxic to SCC cells, but had not effect on bone marrow progenitor cells. Immunoblotting of membrane extracts separated on sodium dodecyl sulfate-polyacrylamide gels showed the LAM8 antigen to have a band of an approximate molecular weight of 135,000 and a cluster of bands with approximate molecular weights of 90,000. This reactivity was lost after incubation of the extracts with periodate. LAM8 antibody shows a highly preferential reactivity with SCC cell lines and formalin-fixed paraffin-embedded SCC tissues and is selectively cytotoxic to cells expressing LAM8 antigen.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2015-01-01

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

  14. 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.

  15. 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.

  16. Erlotinib Pretreatment Improves Photodynamic Therapy of Non-Small Cell Lung Carcinoma Xenografts via Multiple Mechanisms.

    PubMed

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

    2015-08-01

    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. Although EGFR is currently a favorite molecular target for the 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 with 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.

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

    PubMed

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

    2016-02-15

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

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

    PubMed Central

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

    2015-01-01

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

  19. Utility of GATA3 immunohistochemistry in differentiating urothelial carcinoma from prostate adenocarcinoma and squamous cell carcinomas of the uterine cervix, anus, and lung.

    PubMed

    Chang, Alex; Amin, Ali; Gabrielson, Edward; Illei, Peter; Roden, Richard B; Sharma, Rajni; Epstein, Jonathan I

    2012-10-01

    Distinguishing invasive high-grade urothelial carcinoma (UC) from other carcinomas occurring in the genitourinary tract may be difficult. The differential diagnosis includes high-grade prostatic adenocarcinoma, spread from an anal squamous cell carcinoma (SCC), or spread from a uterine cervical SCC. In terms of metastatic UC, the most common problem is differentiating spread of UC to the lung from a primary pulmonary SCC. Immunohistochemical analysis (IHC) for GATA binding protein 3 (GATA3), thrombomodulin (THROMBO), and uroplakin III was performed on a tissue microarray (TMA) containing 35 cases of invasive high-grade UC. GATA3 IHC was also performed on TMAs containing 38 high-grade (Gleason score ≥8) prostatic adenocarcinomas, representative tissue sections from 15 invasive anal SCCs, representative tissue sections from 19 invasive cervical SCCs, and TMAs with 12 invasive cervical carcinomas of the cervix [SCC (n=10), SCC with neuroendocrine features (n=1), and adenosquamous carcinoma (n=1)]. In addition, GATA3 IHC was performed on representative tissue sections from 15 pulmonary UC metastases and a TMA with 25 SCCs of the lung and 5 pulmonary non-small cell carcinomas with squamous features. GATA3, THROMBO, and uroplakin III were positive in 28 (80%), 22 (63%), and 21 (60%) cases of high-grade UC, respectively. All cases of GATA3-positive staining were nonfocal; 25 (89%) cases demonstrated moderate to strong staining, and 3 (11%) demonstrated weak staining. Of the 7 cases that failed to express GATA3, 5 were positive for THROMBO and/or uroplakin III, whereas 2 were negative for all 3 markers. None of the 38 high-grade prostatic adenocarcinomas was positive for GATA3. Weak GATA3 staining was present in occasional basal cells of benign prostate glands, in a few benign atrophic glands, and in urothelial metaplasia. Of the 15 cases of anal SCCs, 2 (7%) cases showed focal weak staining, and 1 (3%) showed focal moderate staining. Weak staining was also rarely

  20. Significance of DEK overexpression for the prognostic evaluation of non-small cell lung carcinoma.

    PubMed

    Liu, Xin; Qi, Dongdong; Qi, Jujie; Mao, Zeshu; Li, Xiangdan; Zhang, Jinhui; Li, Jinzi; Gao, Wenbin

    2016-01-01

    In the present study, we explored the role of DEK expression for the prognostic evaluation of non-small cell lung carcinoma (NSCLC). DEK protein and mRNA expression levels were detected in NSCLC cells and fresh tissue samples of NSCLC paired with adjacent non-tumor tissues, respectively. NSCLC cases (n=196) meeting strict follow-up criteria were selected for immunohistochemical staining of DEK protein. Correlations between DEK expression and clinicopathological features of the NSCLC cases were evaluated using Chi-square tests. Survival rates were calculated using the Kaplan-Meier method, and the relationship between prognostic factors and patient overall survival was analyzed using Cox proportional hazard analysis. Based on the results, the levels of DEK protein and mRNA were significantly upregulated in 6 fresh tissue samples of NSCLC. Immunohistochemical analysis showed that the DEK expression rate was significantly higher in the NSCLC samples compared with either the adjacent non-tumor tissues or normal lung tissues. DEK expression was correlated with poor differentiation and late pathological stage of NSCLC. DEK expression was also correlated with low disease-free survival and overall survival rates. In the early-stage group, disease-free and overall survival rates of patients with DEK expression were significantly lower than those of patients without DEK expression. Further analysis using a Cox proportional hazard regression model revealed that DEK expression emerged as a significant independent hazard factor for the overall survival rate of patients with NSCLC. Consequently, DEK plays an important role in the progression of NSCLC. DEK may potentially be used as an independent biomarker for the prognostic evaluation of NSCLC.

  1. 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.

  2. 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

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

    PubMed

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

    2015-06-01

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

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

    PubMed Central

    Russell, Prudence Anne

    2015-01-01

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

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

    PubMed

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

    2015-03-01

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

  6. 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.

  7. Photothermal therapy of Lewis lung carcinoma in mice using gold nanoshells on carboxylated polystyrene spheres

    NASA Astrophysics Data System (ADS)

    Liu, Huiyu; Chen, Dong; Tang, Fangqiong; Du, Gangjun; Li, Linlin; Meng, Xianwei; Liang, Wei; Zhang, Yangde; Teng, Xu; Li, Yi

    2008-11-01

    A new approach towards the design of gold nanoshells on carboxylated polystyrene spheres (GNCPSs) is reported here. Gold nanoshells were self-assembled on the surface of carboxylated polystyrene spheres by a seed growth method. Chitosan (CHI) was used as a functional agent of carboxylated polystyrene spheres for attaching gold seeds. The surface plasmon resonance (SPR) peak of GNCPSs can be tuned, greatly redshifted, over a broad spectral range including the near-infrared (NIR) wavelength region, which provides maximal penetration of light through tissue. Irradiation of GNCPSs at their peak extinction coefficient results in the conversion of light to heat energy that produces a local rise in temperature. Our study revealed that the Lewis lung carcinoma (LLC) in mice treated with GNCPSs exposed to a low dose of NIR light (808 nm, 4 W cm-2) induced irreversible tissue damage. The tumor volumes of the treatment group by GNCPSs were significantly lower than those of control groups, with an average inhibition rate over 55% (P<0.005). This study proves that GNCPSs are promising in plasmonic photothermal tumor therapy.

  8. 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

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

    PubMed

    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

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

    PubMed Central

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

    2016-01-01

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

  11. 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.

  12. 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.

  13. 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

  14. 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

  15. Modulation of oxidative stress by functionalized fullerene materials in the lung tissues of female C57/BL mice with a metastatic Lewis lung carcinoma.

    PubMed

    Jiao, Fang; Qu, Ying; Zhou, Guoqiang; Liu, Ying; Li, Wei; Ge, Cuicui; Li, Yufeng; Hu, Wei; Li, Bai; Gao, Yuxi; Chen, Chunying

    2010-12-01

    Oxidative stress is considered to be one of the important mechanisms involved in carcinogenesis. To investigate the effect of [Gd@C82(OH)22]n and [C60(OH)20]n nanoparticles on the oxidative stress in the tumor-bearing mice, several antioxidative enzymes and antioxidants were tested for mice with or without tumor inoculation. Transplanted tumors were grown in mice by subcutaneous inoculation of a metastatic Lewis lung carcinoma in female C57/BL mice. More importantly, the tumor cells can metastasize into the normal lung tissues gradually. Therefore, in present paper, the activities of copper-zinc superoxide dismutase (CuZn-SOD), glutathione peroxidase (GSH-Px), glutathione S-transferase (GST), as well as the levels of reduced glutathione (GSH) and malondialdehyde (MDA) in the tumor-invaded lung tissues of the tumor-bearing mice were compared to the nomal lung tissues of normal mice. After treatment with nanoparticles, the activities of GSH-Px and GST and other parameters related to the oxidative stress were downregulated and tended closely to the normal levels. Pulmonary histopathological results also showed that two different types of water-soluble fullerenes can prevent lungs from inflammatory lesion and tumor invasion. These findings indicate two different types of water-soluble fullerenes materials can downregulate the oxidative stress status by scavenging excessive free radicals and inhibiting the lipid peroxidation in tumor-bearing mice, which can partly explain their protective roles on the pulmonary oxidative-damage induced by the tumor metastasis to lung tissues.

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

    ClinicalTrials.gov

    2016-06-17

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

  17. Comparative analyses of individual and multiple alterations of p53, PTEN and p16 in non-small cell lung carcinoma, glioma and breast carcinoma samples.

    PubMed

    Stankovic, Tijana; Milinkovic, Vedrana; Bankovic, Jasna; Dinic, Jelena; Tanic, Nasta; Dramicanin, Tatjana; Tanic, Nikola

    2014-06-01

    p53, p16 and PTEN are the most commonly altered tumor suppressor genes in human cancers. In the present study, we compared the presence of individual and multiple alterations of these tumor suppressors in non-small cell lung carcinoma (NSCLC), glioma and breast carcinoma, in order to evaluate specificity of each tumor type regarding the number of altered genes, as well as their combinations. We tested the mutational status, loss of heterozygosity and methylation status of these genes. Effects of gene alterations on patients' survival were also assessed. In NSCLC samples, single gene alterations occurred rarely, while there was considerable increase in incidence of double gene alterations. Furthermore, coexistence of aberrant p53, PTEN and p16 was the most frequent and had significant adverse effect on the survival of NSCLC patients. On the contrary, in glioma and breast cancer specimens, substantial number of cases had aberrant single gene only. Moreover, glioma and breast carcinoma also differ in genotypes that were predominant. Specifically, in glioma samples, prevalent were co-alterations of PTEN and p16, followed by aberrant only PTEN. In breast cancer samples, alterations in all three genes as well as in p53 and p16 were the most common. Moreover, PTEN was altered exclusively with aberrant p53, with statistically significant correlation among them. Overall, our results suggest that NSCLC, glioma and breast cancer need different approaches in molecular diagnosis and treatment with particular attention toward the number and combination of targeted genes. PMID:24767865

  18. Efficacy of short-term nivolumab treatment in a Chinese patient with relapsed advanced-stage lung squamous cell carcinoma

    PubMed Central

    Pi, Guoliang; He, Hanping; Bi, Jianping; Li, Ying; Li, Yanping; Zhang, Yong; Wang, Mingwei; Han, Guang; Lin, Chi

    2016-01-01

    Abstract Introduction: Currently, the options are limited for the treatment of patients who have failed 2 lines of chemotherapy for advanced lung squamous cell carcinoma (SCC). Recently, nivolumab, a fully human IgG4 programmed death 1 immune checkpoint inhibitor antibody, was approved to treat patients with advanced stage, relapsed/refractory lung SCC. Although nivolumab has demonstrated antitumor activity with survival benefit in Caucasian patients, its efficacy in Asian patients is unknown. Case Report: In this report, we describe a Chinese patient with relapsed advanced stage lung SCC who had an excellent response to nivolumab after only 2 doses without any adverse effects. Immunohistochemical analysis indicated the tumor was stained positive for programmed death-ligand 1. Conclusion: To our knowledge, this is the first report of satisfactory efficacy of short-term nivolumab treatment in a Chinese patient with relapsed advanced-stage lung SCC. Further clinical trials in Asian countries are needed to test whether nivolumab immunotherapy is a safe and effective treatment for Asian patients with lung SCC. PMID:27749580

  19. Elevated GAPDH expression is associated with the proliferation and invasion of lung and esophageal squamous cell carcinomas.

    PubMed

    Hao, Lihong; Zhou, Xin; Liu, Shuqing; Sun, Mingzhong; Song, Yang; Du, Sha; Sun, Bing; Guo, Chunmei; Gong, Linlin; Hu, Jun; Guan, Hongwei; Shao, Shujuan

    2015-09-01

    Glyceraldehyde-3-phosphate dehydrogenase, is one of the most investigated housekeeping genes and widely used as an internal control in analysis of gene expression levels. The present study was designed to assess whether GAPDH is associated with cancer cell growth and progression and, therefore may not be a good internal control in cancer research. Our results from clinical tissue studies showed that the levels of GAPDH protein were significantly up-regulated in lung squamous cell carcinoma tissues, compared with the adjacent normal lung tissues, and this was confirmed by western blotting and immunohistochemistry. GAPDH knockdown by siRNA resulted in significant reductions in proliferation, migration, and invasion of lung squamous carcinoma cells in vitro. In a nude mouse cancer xenograft model, GAPDH knockdown significantly inhibited the cell proliferation and migration/invasion in vivo. In summary, GAPDH may not be an appropriate internal control for gene expression studies, especially in cancer research. The role of GAPDH in cancer development and progression should be further examined in pre-clinical and clinical studies. PMID:25944651

  20. Curcumin reduces trabecular and cortical bone in naive and lewis lung carcinoma-bearing mice.

    PubMed

    Yan, Lin; Yee, John A; Cao, Jay

    2013-08-01

    The present study investigated the effects of curcumin on bone microstructure in non-tumor-bearing and Lewis lung carcinoma-(LLC)-bearing female C57BL/6 mice. Morphometric analysis showed that dietary supplementation with curcumin (2% or 4%) significantly reduced the bone volume to total volume ratio, connectivity density and trabecular number, and significantly increased the structure model index (an indicator of the plate- and rod-like geometry of trabecular structure) and trabecular separation in vertebral bodies compared to controls in both non-tumor-bearing and LLC-bearing mice. Similar changes in trabecular bone were observed in the femoral bone in curcumin-fed mice. Curcumin significantly reduced the cortical bone area to total area ratio and cortical thickness in femoral mid-shaft, but not in vertebral bodies, in both non-tumor-bearing and LLC-bearing mice. Curcumin feeding reduced plasma concentrations of osteocalcin and increased tartrate-resistant acid phosphate 5b in mice regardless of the presence of LLC, indicating that curcumin disrupts the balance of bone remodeling. Our results demonstrated that curcumin reduced the trabecular bone volume and cortical bone density. The skeleton is a favored site of metastasis for many types of cancers, and curcumin has been investigated in clinical trials in patients with cancer for its chemopreventive effects. Our results suggest the possibility of a combined effect of cancer-induced osteolysis and curcumin-stimulated bone loss in patients using curcumin. The assessment of bone structural changes should be considered for those who participate in curcumin clinical trials to determine its effects on skeleton health, particularly for those with advanced malignancies.

  1. Novel Humoral Prognostic Markers in Small-Cell Lung Carcinoma: A Prospective Study

    PubMed Central

    Gozzard, Paul; Chapman, Caroline; Vincent, Angela; Lang, Bethan; Maddison, Paul

    2015-01-01

    Purpose Favourable small cell lung carcinoma (SCLC) survival outcomes have been reported in patients with paraneoplastic neurological disorders (PNDs) associated with neuronal antibodies (Neur-Abs), but the presence of a PND might have expedited diagnosis. Our aim was to establish whether neuronal antibodies, independent of clinical neurological features, correlate with SCLC survival. Experimental Design 262 consecutive SCLC patients were examined: of these, 24 with neurological disease were excluded from this study. The remaining 238 were tested for a broad array of Neur-Abs at the time of cancer diagnosis; survival time was established from follow-up clinical data. Results Median survival of the non-PND cohort (n = 238) was 9.5 months. 103 patients (43%) had one or more antigen-defined Neur-Abs. We found significantly longer median survival in 23 patients (10%) with HuD/anti-neuronal nuclear antibody type 1 (ANNA-1, 13.0 months P = 0.037), but not with any of the other antigen-defined antibodies, including the PND-related SOX2 (n = 56, 24%). An additional 28 patients (12%) had uncharacterised anti-neuronal nuclear antibodies (ANNA-U); their median survival time was longer still (15.0 months, P = 0.0048), contrasting with the survival time in patients with non-neuronal anti-nuclear antibodies (detected using HEp-2 cells, n = 23 (10%), 9.25 months). In multivariate analyses, both ANNA-1 and ANNA-U independently reduced the mortality hazard by a ratio of 0.532 (P = 0.01) and 0.430 (P<0.001) respectively. Conclusions ANNAs, including the newly described ANNA-U, may be key components of the SCLC immunome and have a potential role in predicting SCLC survival; screening for them could add prognostic value that is similar in magnitude to that of limited staging at diagnosis. PMID:26606748

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

    PubMed

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

    2015-07-01

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

  3. Surgical treatment of small cell carcinoma of the lung: advantage of preoperative chemotherapy.

    PubMed

    Wada, H; Yokomise, H; Tanaka, F; Hirata, T; Fukuse, T; Bando, T; Inui, K; Ike, O; Mizuno, H; Hitomi, S

    1995-08-01

    To assess the effect of chemotherapy on postoperative survival of patients with small cell lung carcinoma (SCLC), 46 patients who underwent surgery at Kyoto University between 1976 and 1991 were retrospectively reviewed. Seventeen patients (37.0%) received chemotherapy prior to as well as after surgery (neoadjuvant therapy group), 23 (50.5%) received chemotherapy only after surgery (adjuvant therapy group), and the other six received no chemotherapy (non-chemotherapy group). The 5-year survival rate of patients with c-Stage I or II disease in the neoadjuvant therapy group was as high as 80.0%, which seemed to be higher, although with no statistical significance, than that in the adjuvant therapy group (37.7%, P = 0.10). The 5-year survival rate of patients with c-Stage III (IIIa or IIIb) disease in the neoadjuvant therapy group, although not satisfactory (10.0%), was significantly higher than that in the adjuvant therapy group (0.0%, P = 0.04). No patients in the non-chemotherapy group had survived 5 years. Moreover, multivariate analysis showed that failure to employ preoperative chemotherapy was the strongest prognostic factor causing a poor prognosis (P = 0.01). On the other hand, eight (30.8%) out of 26 patients with c-Stage I or II disease postoperatively proved to have mediastinal lymph node involvement (pN2-3), and two (7.7%) proved to have intrapulmonary metastasis (PM). Considering the advantage of preoperative chemotherapy and the discrepancy between c- and p-stage, sufficient chemotherapy prior to surgery should be employed, and may realize a good prognosis in patients with c-Stage I or II disease. In contrast, patients with c-Stage III disease are not appropriate as candidates for surgery even if preoperative chemotherapy is performed.

  4. ALK status testing in non-small cell lung carcinoma: correlation between ultrasensitive IHC and FISH.

    PubMed

    Minca, Eugen C; Portier, Bryce P; Wang, Zhen; Lanigan, Christopher; Farver, Carol F; Feng, Yan; Ma, Patrick C; Arrossi, Valeria A; Pennell, Nathan A; Tubbs, Raymond R

    2013-05-01

    ALK gene rearrangements in advanced non-small cell lung carcinomas (NSCLC) are an indication for targeted therapy with crizotinib. Fluorescence in situ hybridization (FISH) using a recently approved companion in vitro diagnostic class FISH system commonly assesses ALK status. More accessible IHC is challenged by low expression of ALK-fusion transcripts in NSCLC. We compared ultrasensitive automated IHC with FISH for detecting ALK status on 318 FFPE and 40 matched ThinPrep specimens from 296 patients with advanced NSCLC. IHC was concordant with FFPE-FISH on 229 of 231 dual-informative samples (31 positive and 198 negative) and with ThinPrep-FISH on 34 of 34 samples (5 positive and 29 negative). Two cases with negative IHC and borderline-positive FFPE-FISH (15% and 18%, respectively) were reclassified as concordant based on negative matched ThinPrep-FISH and clinical data consistent with ALK-negative status. Overall, after including ThinPrep-FISH and amending the false-positive FFPE-FISH results, IHC demonstrated 100% sensitivity and specificity (95% CI, 0.86 to 1.00 and 0.97 to 1.00, respectively) for ALK detection on 249 dual-informative NSCLC samples. IHC was informative on significantly more samples than FFPE-FISH, revealing additional ALK-positive cases. The high concordance with FISH warrants IHC's routine use as the initial component of an algorithmic approach to clinical ALK testing in NSCLC, followed by reflex FISH confirmation of IHC-positive cases. PMID:23499337

  5. 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.

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

    PubMed

    Maca, R D

    1988-12-01

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

  7. Chemotherapy in vivo against M109 murine lung carcinoma with cytochalasin B by localized, systemic, and liposomal administration.

    PubMed

    Trendowski, Matthew; Mitchell, Joan M; Corsette, Christine M; Acquafondata, Christopher; Fondy, Thomas P

    2015-04-01

    Cytochalasin B is a potentially novel microfilament-directed chemotherapeutic agent that prevents actin polymerization, thereby inhibiting cytokinesis. Although cytochalasin B has been extensively studied in vitro, only limited data are available to assess its in vivo potential. Cytochalasin B was administered to Balb/c mice challenged i.d. with M109 murine lung carcinoma to determine whether the agent could affect an established i.d. tumor when the compound is administered s.c. in the region of the i.d. tumor, but not in direct contact with it. Cytochalasin B was also administered either i.p. or s.c. at a distant site or i.v. to determine whether it could affect the long-term development of an established i.d. tumor. Cytochalasin B was then liposome encapsulated to determine whether the maximum tolerated dose (MTD) of the compound could be increased, while reducing immunosuppression that we have previously characterized. Liposomal cytochalasin B was also administered to mice challenged i.d. with M109 lung carcinoma to assess its chemotherapeutic efficacy. The results can be summarized as follows: 1) cytochalasin B substantially delayed the growth of i.d. M109 tumor nodules, inhibited metastatic progression in surrounding tissues, and produced long-term cures in treated mice; 2) liposomal cytochalasin B increased the i.p. MTD by more than 3-fold, produced a different distribution in tissue concentrations, and displayed antitumor effects against M109 lung carcinoma similar to non-encapsulated cytochalasin B. These data show that cytochalasin B exploits unique chemotherapeutic mechanisms and is an effective antineoplastic agent in vivo in pre-clinical models, either in bolus form or after liposome encapsulation.

  8. 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.

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

    PubMed

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

    2016-06-01

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

  10. Small-cell carcinoma of the lung: patterns of treatment failure in patients treated primarily by chemotherapy

    SciTech Connect

    Ali, M.M.; Hazra, T.A.

    1984-08-01

    Treatment failure patterns in 75 patients with small-cell carcinoma of the lung who were treated primarily by chemotherapy were reviewed. Of 32 patients with disease considered to be localized but who did not undergo complete staging work-ups, 23 had metastasis to the chest, 11 to the central nervous system, four to bone, and two to the lymph nodes. Of 33 patients with documented distant metastasis, 23 had metastasis to the chest, 14 to the central nervous system, 15 to bone, and six to the lymph nodes. Median survival times of patients showing complete response to treatment was 17 months; for those showing partial response it was 7 months.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-06-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-04-26

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

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

    ClinicalTrials.gov

    2016-08-25

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

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

    ClinicalTrials.gov

    2016-10-14

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

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

    PubMed

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

    2015-11-01

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

  18. 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

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

    PubMed

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

    2004-03-01

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

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

    PubMed Central

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

    2013-01-01

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

  1. Cavitary mucoepidermoid carcinoma of lung with metastases in skeletal muscles as presenting features: a case report and review of the literature.

    PubMed

    Singh, Abhishek; Pandey, Kailash C; Pant, Nirdosh K

    2010-01-01

    Mucoepidermoid carcinomas (MECs) of lung are rare neoplasms originating in bronchial submucosal glands and comprising 0.1-0.2% of primary lung cancers. MECs, the most common malignancy in salivary glands, were earlier thought to occur only in salivary glands. Later studies showed that they can arise as a primary in bronchus, esophagus, lacrimal glands, pancreas, thymus and thyroid gland. Initially described as a benign adenoma, it is now considered to be a malignant epithelial tumor. There have been reports of metastases to regional lymph nodes, other parts of the lung and distant organs. Cavitary lesion in MEC of lung is rare. Here, we report a case of MEC of lung with metastases to skeletal muscles of thigh and arm. To the best of our knowledge, this is the only case of MEC of lung presenting with such unusual pattern of metastasis as presenting feature with almost no symptoms of primary lesion. PMID:21119274

  2. Cavitary mucoepidermoid carcinoma of lung with metastases in skeletal muscles as presenting features: a case report and review of the literature.

    PubMed

    Singh, Abhishek; Pandey, Kailash C; Pant, Nirdosh K

    2010-01-01

    Mucoepidermoid carcinomas (MECs) of lung are rare neoplasms originating in bronchial submucosal glands and comprising 0.1-0.2% of primary lung cancers. MECs, the most common malignancy in salivary glands, were earlier thought to occur only in salivary glands. Later studies showed that they can arise as a primary in bronchus, esophagus, lacrimal glands, pancreas, thymus and thyroid gland. Initially described as a benign adenoma, it is now considered to be a malignant epithelial tumor. There have been reports of metastases to regional lymph nodes, other parts of the lung and distant organs. Cavitary lesion in MEC of lung is rare. Here, we report a case of MEC of lung with metastases to skeletal muscles of thigh and arm. To the best of our knowledge, this is the only case of MEC of lung presenting with such unusual pattern of metastasis as presenting feature with almost no symptoms of primary lesion.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

    Dalby, Andrew; Bailey, Ian

    2014-01-01

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

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

    PubMed Central

    Sadava, David; Kane, Susan E.

    2014-01-01

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

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

    PubMed

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

    2015-11-01

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

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

    PubMed

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

    2015-11-01

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

  8. Gamma-amino butyric acid inhibits the nicotine-imposed stimulatory challenge in xenograft models of non-small cell lung carcinoma.

    PubMed

    Al-Wadei, H A N; Al-Wadei, M H; Ullah, M F; Schuller, H M

    2012-02-01

    Non-small cell lung carcinoma (NSCLC) is the leading type of lung cancer; smoking is a documented risk factor. Nicotinic acetylcholine receptor (nAChR)-mediated intracellular signaling in response to nicotine has recently been implicated in the growth regulation of NSCLC. In the current study nude mice carrying xenografts of the human lung NSCLC cell lines NCI-H322 or NCI-H441 were used as animal models. Nicotine administration and gamma aminobutyric acid (GABA) treatment lasted for 30 days. Catecholamines, cortisol, GABA, and cAMP were analyzed in blood and tumor tissues by immunoassays. Expression of nicotinic receptors and effector proteins in the xenografts was assessed by Western blotting. Our data indicate that nicotine stimulated the growth of NSCLC xenografts via modulation of nAChR upregulation and activation of cAMP signaling. The nicotine-treated group showed an enhanced level of stress neurotransmitters and second messenger cAMP in serum, blood cellular fraction, and xenograft tissues. Activation of critical proteins in the oncogenic pathway, including CREB, ERK, Akt, and Src, and upregulation of α-4 and α-7 subunits of nAChR provided mechanistic insight for the observed stimulatory effect of nicotine. Interestingly, GABA, being an antagonist to cAMP signaling, showed a promising intervention by reversing the stimulatory effect of nicotine on cancer growth and all signaling pathways. GABA has potential to lower the risk of NSCLC among smokers and could be used to enhance the clinical outcome of standard cancer intervention strategies.

  9. 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

  10. Synchronous Primary Lung Cancer Presenting with Small Cell Carcinoma and Adenocarcinoma

    PubMed Central

    Kodama, Ken; Yamato, Hiroyuki; Takeda, Masashi; Takamori, Hiroyuki; Karasuno, Takahiro

    2015-01-01

    Multiple synchronous primary lung cancers presenting with different histologic types are uncommon. Among reported cases with different histologic findings, only a few had small cell lung cancer (SCLC) and adenocarcinoma. This unusual combination of lung cancers has not been well reported. In this report, we describe two cases of synchronous primary lung cancer presenting with lymph node metastasis of SCLC and early-stage adenocarcinoma. Epidermal growth factor receptor (EGFR) mutation was not detected in either SCLC or adenocarcinoma in the two cases. PMID:25832826

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

    PubMed Central

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

    1983-01-01

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

  12. Disseminated Skeletal Muscle and Cardiac Metastasis from Squamous Cell Carcinoma of the Lung Detected with FDG and FLT PET/CT

    PubMed Central

    Jain, Tarun Kumar; Rayamajhi, Sampanna Jung; Basher, Rajender Kumar; Gupta, Dheeraj; Maturu, Venkata Nagarjuna; Mittal, Bhagwant Rai

    2016-01-01

    Lung cancer is one of the leading cancers all over the world. Positron emission tomography (PET) using 18F fluorodeoxyglucose (18F FDG) is useful for staging of the disease and decide the appropriate management. 3’-deoxy-3’-18 F-fluorothymidine (18F FLT) is a tracer being extensively evaluated currently and is said to represent tumor proliferation. Common sites of metastases from lung cancer include adrenal glands, bone, and brain. Muscle metastasis and cardiac metastasis are uncommon findings. We report a case of squamous cell carcinoma of the lung with metastases to multiple skeletal muscles and myocardium detected with both FDG and FLT PET/computed tomography (CT).

  13. Disseminated Skeletal Muscle and Cardiac Metastasis from Squamous Cell Carcinoma of the Lung Detected with FDG and FLT PET/CT.

    PubMed

    Jain, Tarun Kumar; Rayamajhi, Sampanna Jung; Basher, Rajender Kumar; Gupta, Dheeraj; Maturu, Venkata Nagarjuna; Mittal, Bhagwant Rai

    2016-09-01

    Lung cancer is one of the leading cancers all over the world. Positron emission tomography (PET) using 18F fluorodeoxyglucose (18F FDG) is useful for staging of the disease and decide the appropriate management. 3'-deoxy-3'-18 F-fluorothymidine (18F FLT) is a tracer being extensively evaluated currently and is said to represent tumor proliferation. Common sites of metastases from lung cancer include adrenal glands, bone, and brain. Muscle metastasis and cardiac metastasis are uncommon findings. We report a case of squamous cell carcinoma of the lung with metastases to multiple skeletal muscles and myocardium detected with both FDG and FLT PET/computed tomography (CT). PMID:27651747

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    PubMed Central

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

    2016-01-01

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

  19. [A case of large cell carcinoma of the lung associated with a sarcoid-like reaction inside the tumor].

    PubMed

    Kudo, Keita; Sakamoto, Susumu; Miyamoto, Atushi; Kono, Tadasu; Motoi, Noriko; Yoshimura, Kunihiko

    2008-11-01

    A sarcoid-like reaction may occur inside a malignant tumor, in regional lymph-nodes or in adjacent tissues. An 83 year-old man who was found to have a mass in his left lower lung field on a chest radiograph. Transbronchial biopsy was performed and a non-caseating granulomatous lesion caused by a possible infectious disease was diagnosed. However, the size of the mass increased after 6 months. The patient was referred to our hospital, and lung biopsy under video-assisted thoracoscopic surgery (VATS) was performed. Since the initial intraoperative pathologic examination showed the presence of non-caseating epithelioid cell granulomas, only partial resection was conducted. However, detailed postoperative histopathological evaluation led to a diagnosis of large cell carcinoma of the lung associated with an internal sarcoid-like reaction. The patient then received another VATS for left lower lobectomy. Formation of epithelioid cell granulomas within a tumor is quite rare. In cases in which the pathological findings of TBLB specimens do not agree with the clinical course, more thorough approaches such as biopsy under VATS may be required.

  20. 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

  1. Exercise performance after standard rehabilitation in COPD patients with lung hyperinflation.

    PubMed

    Crisafulli, Ernesto; Venturelli, Elena; Biscione, Gianluca; Vagheggini, Guido; Iattoni, Andrea; Lucic, Sasha; Ambrosino, Nicolino; Pasqua, Franco; Cesario, Alfredo; Clini, Enrico Maria

    2014-02-01

    The role of pulmonary rehabilitation (PR) in COPD patients with lung hyperinflation has not yet been fully investigated. We retrospectively evaluated the effect of a standard PR course on exercise tolerance and symptoms according to the presence or absence of associated lung hyperinflation, as defined by lung function parameters in three Italian rehabilitation centres. In a cohort of 823 COPD patients (age 71 ± 8 years, FEV1 56 ± 18% pred.) we have systematically recorded: changes (∆) in 6-minute walking test (6MWD) as the primary outcome; dyspnoea (D); muscle fatigue (F); SO2nadir during effort; perceived breathlessness score (MRC); and specific health-related quality of life (SGRQ). Outcomes were compared between patients with lung hyperinflation (n = 283, LH) or without (n = 540 No-LH). Groups were comparable for age, body mass index, baseline exercise tolerance, and breathlessness. ∆-6MWD (+72 ± 47 vs. +62 ± 42 m, p < 0.05); ∆-D (-2.3 ± 1.7 vs. -1.9 ± 1.3 point, p < 0.05) and ∆-SO2nadir (+1.4 ± 3.0 and +0.5 ± 3.3 point, p < 0.05) were greater in LH than in No-LH. Using a multivariate linear regression model, ∆-6MWD in the LH group significantly correlated with lower functional residual capacity (p = 0.021) and baseline 6MWD (p = 0.004). Tolerance, gas exchange and perceived symptoms during effort are the parameters that gain a significant benefit from standard rehabilitation in COPD patients with a lung hyperinflation condition.

  2. Down-regulation of cytoplasmic PLZF correlates with high tumor grade and tumor aggression in non-small cell lung carcinoma.

    PubMed

    Xiao, Guang-Qian; Li, Faqian; Findeis-Hosey, Jennifer; Hyrien, Ollivier; Unger, Pamela D; Xiao, Lu; Dunne, Richard; Kim, Eric S; Yang, Qi; McMahon, Loralee; Burstein, David E

    2015-11-01

    There are currently no effective prognostic biomarkers for lung cancer. Promyelocytic leukemia zinc finger (PLZF), a transcriptional repressor, has a role in cell cycle progression and tumorigenicity in various cancers. The expression and value of PLZF in lung carcinoma, particularly in the subclass of non-small cell lung carcinoma (NSCLC), has not been studied. Our aim was to study the immunohistochemical expression of PLZF in lung adenocarcinoma and squamous cell carcinoma and correlate the alteration of PLZF expression with tumor differentiation, lymph node metastasis, tumor stage, and overall survival. A total of 296 NSCLCs being mounted on tissue microarray (181 adenocarcinomas and 91 squamous cell carcinomas) were investigated. Moderate to strong expression of PLZF was found in the cytoplasm of all the nonneoplastic respiratory epithelium and most (89.9%) well-differentiated adenocarcinoma. The proportions of moderately differentiated, poorly differentiated adenocarcinoma, and paired lymph node adenocarcinoma metastases that demonstrated negative or only weak PLZF reactivity were 75.6%, 97.2%, and 89.9%, respectively. The expression of PLZF in squamous cell carcinoma was mostly weak or absent and significantly lower than that in adenocarcinoma of the same grade (P < .0005). The loss of cytoplasmic PLZF strongly correlated with high tumor grade and lymph node metastasis in both squamous carcinoma and adenocarcinoma (P < .0001). Down-regulation of PLZF also correlated with higher tumor stage and shorter overall survival (P < .05). These results support a prognostic value for loss of cytoplasmic PLZF expression in the stratification of NSCLC and a possible role of cytoplasmic shift and down-regulation of PLZF in the pathogenesis of NSCLC.

  3. 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

  4. 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.

  5. Relationship between bronchiolar dose and lung carcinoma induction following inhalation of /sup 239/PuO/sub 2/ in rats

    SciTech Connect

    Sanders, C.L.; Lauhala, K.E.; McDonald, K.E.

    1988-08-01

    This manuscript describes preliminary observations in a lifespan and serial sacrifice study with 3332 female, Wistar rats exposed to high-fired /sup 239/PuO/sub 2/ aerosols. Sufficient numbers of sham-control and low dose (equivalent to maximal permissible occupational lung deposition of 0.6 kBq in standard man) animals are provided to statistically estimate lung cancer risk and define the cellular-microdosimetric relationships leading to lung tumor formation. Whole-body counting for /sup 169/Yb tagged /sup 239/PuO/sub 2/ aerosol provided a very accurate method for determining Pu ILB in individual rats (Sanders et al., 1986). The experimental design, methodology and early results of the lifespan study have been previously reported (Sanders et al., 1986, 1988a). 7 refs., 3 figs.

  6. Synchronous bilateral squamous cell carcinoma of the lung successfully treated using intensity-modulated radiotherapy

    PubMed Central

    Loo, S W; Smith, S; Promnitz, D A; Van Tornout, F

    2012-01-01

    We present a case of synchronous bilateral inoperable lung cancer which required treatment with external beam radiotherapy to a radical dose. Intensity-modulated radiotherapy (IMRT) was used. More conformal dose distribution within the planning target volume was obtained using IMRT than the conventional technique. Dose–volume constraints defined for the lungs were met. Treatment was subsequently delivered using a seven-field IMRT plan. The patient remains alive and disease-free 48 months after the completion of radiotherapy. IMRT can be considered an effective treatment for synchronous bilateral lung cancer. PMID:21937610

  7. Rapid on-site evaluation has high diagnostic yield differentiating adenocarcinoma vs squamous cell carcinoma of non-small cell lung carcinoma, not otherwise specified subgroup.

    PubMed

    Celik, Betul; Khoor, Andras; Bulut, Tangul; Nassar, Aziza

    2015-01-01

    Our objective was to evaluate the diagnostic yield of rapid on-site evaluation (ROSE) on the differential diagnosis of non-small cell lung carcinoma, not otherwise specified (NSCLC-NOS). Biopsied cases diagnosed as NSCLC-NOS with ROSE during 2004 through 2008 were retrieved. Diagnostic confirmation was done with immunohistochemistry (IHC) involving thyroid transcription factor-1 and p63 immunostains. For the study, 106 cases were available. The final diagnoses rendered were squamous cell carcinoma (SqCC) (n = 39) and adenocarcinoma (AC) (n = 67). Cytologic, histologic, and IHC concordance for these diagnoses occurred in 75 cases (70.8 %), of which 56 (52.8%) were AC and 19 (17.9%) were SqCC. Cytologic, histologic, and IHC discordance was found in 31 cases (29.2%). Of these 31 cases, 11 NSCLC-NOS diagnoses histologically corresponded to 1 SqCC plus 4 ACs, and 4 favor SqCC plus 2 ACs; the former 5 NSCLC-NOS cases classified correctly through cytology, as well as IHC. However, IHC was not available for the latter 6 NSCLC-NOS cases that were also classified correctly through cytology. In addition, only 3 NSCLC-NOS diagnoses cytologically corresponded to 3 favor SqCC histologically, in which IHC was not available, and for 2 cases that both corresponded to favor SqCC and favor AC histologically and cytologically. In the other 15 cases, histology labeled 4 cases NSCLC-NOS and misclassified 2 cases; cytology labeled 1 case NSCLC-NOS and misclassified 13 cases. ROSE has high diagnostic yield over subclassification of NSCLC-NOS. We recommend allocating a cytotechnologist for specimen adequacy and a cytopathologist for cytologic diagnosis.

  8. Influence of radiation therapy quality control on survival, response and sites of relapse in oat cell carcinoma of the lung

    SciTech Connect

    White, J.E.; Chen, T.; McCracken, J.; Kennedy, P.; Seydel, H.G.; Hartman, G.; Mira, J.; Khan, M.; Durrance, F.Y.; Skinner, O.

    1982-09-15

    Two hundred and ninety-eight patients with limited (confined to chest and supraclavicular area, encompassable by a single radiation portal) small cell carcinoma of the lung were entered on Southwest Oncology Group Protocol 7628. Patients were treated with multi-agent chemotherapy and radiation therapy with or without BCG. Radiation therapy quality control analysis, including dosimetric reconstruction and port film review was introduced after the protocol was activated and was retrospectively applied. Patients who were considered major protocol variations had statistically worse survival (40 weeks versus 60 weeks; P = .002), a lesser improvement in response rate after induction chemotherapy (27 versus 48%; P = .05) and a higher chest failure rate (77 versus 55%; P = .047) than evaluable patients. Five patients relapsed in the brain, all associated with chest failure. Quality control is essential in cooperative group studies.

  9. Intratumor chemotherapy in combination with a systemic antimetastatic drug in the treatment of Lewis-lung carcinoma.

    PubMed

    De-Oliveira, M M; Nakamura, I T; Joussef, A C; Giannotti Filho, O

    1985-01-01

    The effect of an antimetastatic agent plus intratumor chemotherapy was evaluated in mice bearing Lewis-lung carcinoma by measuring survival time and by histological examination. Polymeric flavan-3,4-diol (APF) from avocado seeds, Persea gratissima, administered alone directly into the tumor did not change survival time, although it partially destroyed the primary tumor. However, the drug administered in combination with an antimetastatic, 1,2-bis(3,5-dioxopiperazin-1-yl)ethane (ICRF-154), resulted in an increase in survival time. When 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) was used in place of polymeric flavanadiol as an intralesional drug, a significant increase in survival was also achieved. The effect of each drug alone and of their combination was evaluated by "responder analyses". Animals "cured" by the combination and rechallenged with 2 X 10(6) tumor cells showed that immunization could occur.

  10. 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.

  11. Inhibition of Lewis Lung Carcinoma Growth by Toxoplasma gondii through Induction of Th1 Immune Responses and Inhibition of Angiogenesis

    PubMed Central

    Kim, Ju-Ock; Jung, Sung-Soo; Kim, Sun-Young; Kim, Tae Yun; Shin, Dae-Whan; Lee, Jae-Ho

    2007-01-01

    Toxoplasma gondii is an obligate intracellular protozoan parasite that induces antitumor activity against certain types of cancers. However, little information is available regarding the immunologic mechanisms that regulate these effects. For this purpose, C57BL/6 mice were administered either the T. gondii Me49 strain orally or Lewis lung carcinoma (LLC) cells intramuscularly. Survival rates, tumor size, histopathology, and immune responses were determined for each group, and angiogenesis was evaluated by in vivo Matrigel plug assay. Toxoplasma-infected (TG-injected) mice survived the entire experimental period, whereas cancer cell-bearing (LLC-injected) mice died within six weeks. Mice injected with both T. gondii and cancer cells (TG/LLC-injected group) showed significantly increased survival rates, CD8+ T-cell percentages, IFN-γ mRNA expression levels, serum IgG2a titers, and CTL responses as compared to the LLC-injected mice. In addition, angiogenesis in the TG/LLC-injected mice was notably inhibited. These effects in TG/LCC-injected mice were similar or were increased by the addition of an adjuvant, Quil-A. However, TG/LLC-injected mice showed decreased percentages of CD4+ and CD8+ T-cells, IFN-γ mRNA expression levels, and serum IgG1 and IgG2a titers as compared to TG-injected mice. Taken together, our results demonstrate that T. gondii infection inhibits tumor growth in the Lewis lung carcinoma mouse model through the induction of Th1 immune responses and antiangiogenic activity. PMID:17923753

  12. Acinic cell carcinoma of the lung with metastasis to lymph nodes.

    PubMed

    Ukoha, O O; Quartararo, P; Carter, D; Kashgarian, M; Ponn, R B

    1999-02-01

    A 64-year-old man presented with an asymptomatic left lower lobe mass. At bronchoscopy there was a tumor in the superior segment. Biopsy revealed an acinic cell carcinoma. There was no evidence of salivary gland or other site of origin. Lobectomy and lymph node staging showed involvement of interlobar (N1) nodes, while higher stations were benign. The patient remains well 20 months postoperatively. This is the only instance of primary pulmonary acinic cell carcinoma with lymph node metastasis among 15 cases in the literature. We review the clinical features, histology, and treatment of the reported cases.

  13. An ALK translocation positive carcinoma of the lung presenting as uremia due to bilateral renal obstruction.

    PubMed

    Rosenberg, Shilo; Katz, Ran; Pode, Dov; Gofrit, N Ofer; Pizov, Galina; Hovav, Nechushtan

    2013-01-01

    We describe an unusual presentation of metastatic lung adenocarcinoma as malignant retroperitoneal fibrosis (MRPF). The diagnostic challenge, due to the small solitary lung mass and absence of a discrete retroperitoneal mass, was overcome by diagnostic laparoscopy. Molecular analysis of tissue acquired was positive for ALK gene rearrangement. Treatment of the patient with crizotinib reversed MRPF. He was weaned off the nephrostomy tubes and is with stable renal function 11 months after diagnosis. PMID:23914266

  14. 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

  15. 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 ...

  16. Leucine-rich α-2-glycoprotein promotes TGFβ1-mediated growth suppression in the Lewis lung carcinoma cell lines.

    PubMed

    Takemoto, Norihiko; Serada, Satoshi; Fujimoto, Minoru; Honda, Hiromi; Ohkawara, Tomoharu; Takahashi, Tsuyoshi; Nomura, Shintaro; Inohara, Hidenori; Naka, Tetsuji

    2015-05-10

    Leucine-rich α2-glycoprotein (LRG) is an approximately 50-kDa glycoprotein that has been found to be elevated in the sera of patients with several types of cancer. LRG directly binds to transforming growth factor beta 1 (TGFβ1) and modulates TGFβ1 signaling in endothelial cells; however, the precise function of LRG in cancer remains unclear. This study aimed to investigate the role of LRG in cancer. Lewis lung carcinoma (LLC) cells hardly expressed LRG. The growth of LLC tumors allografted in the LRG knockout (KO) mice was significantly increased compared with wild-type (WT) mice. Conversely, overexpression of LRG significantly inhibited the growth of LLC tumors in WT mice. In the presence of LRG, TGFβ1 significantly inhibited the proliferation of LLC cells and human hepatocellular carcinoma Hep3B cells in vitro by inducing apoptosis via the potent activation of smad2 and its downstream signaling pathway. Furthermore, administration of a TGFβR1 inhibitor (SB431542) significantly enhanced the growth of LLC tumors in WT mice compared with LRG KO mice via inhibition of apoptosis. We propose that LRG potentiates the effect of TGFβ1 in cancer cells whose growth is suppressed in the presence of TGFβ1.

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

    ClinicalTrials.gov

    2016-07-11

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

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

    PubMed

    Vannucci, Fernando; Gonzalez-Rivas, Diego

    2016-10-01

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

  19. 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.

  20. Regulation of TPD52 by antitumor microRNA-218 suppresses cancer cell migration and invasion in lung squamous cell carcinoma

    PubMed Central

    Kumamoto, Tomohiro; Seki, Naohiko; Mataki, Hiroko; Mizuno, Keiko; Kamikawaji, Kazuto; Samukawa, Takuya; Koshizuka, Keiichi; Goto, Yusuke; Inoue, Hiromasa

    2016-01-01

    The development of targeted molecular therapies has greatly benefited patients with lung adenocarcinomas. In contrast, these treatments have had little benefit in the management of lung squamous cell carcinoma (lung SCC). Therefore, new treatment options based on current genomic approaches are needed for lung SCC. Aberrant microRNA (miRNA) expression has been shown to promote lung cancer development and aggressiveness. Downregulation of microRNA-218 (miR-218) was frequently observed in our miRNA expression signatures of cancers, and previous studies have shown an antitumor function of miR-218 in several types of cancers. However, the impact of miR-218 on lung SCC is still ambiguous. The present study investigated the antitumor roles of miR-218 in lung SCC to identify the target genes regulated by this miRNA. Ectopic expression of miR-218 greatly inhibited cancer cell migration and invasion in the lung SCC cell lines EBC-1 and SK-MES-1. Through a combination of in silico analysis and gene expression data searching, tumor protein D52 (TPD52) was selected as a putative target of miR-218 regulation. Moreover, direct binding of miR-218 to the 3′-UTR of TPD52 was observed by dual luciferase reporter assay. Overexpression of TPD52 was observed in lung SCC clinical specimens, and knockdown of TPD52 significantly suppressed cancer cell migration and invasion in lung SCC cell lines. Furthermore, the downstream pathways mediated by TPD52 involved critical regulators of genomic stability and mitotic checkpoint genes. Taken together, our data showed that downregulation of miR-218 enhances overexpression of TPD52 in lung SCC cells, promoting cancer cell aggressiveness. Identification of tumor-suppressive miRNA-mediated RNA networks of lung SCC will provide new insights into the potential mechanisms of the molecular pathogenesis of the disease. PMID:27633630

  1. Exome sequencing identifies frequent mutation of MLL2 in non-small cell lung carcinoma from Chinese patients.

    PubMed

    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

  2. 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.

  3. 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.

  4. Novel Candidate Key Drivers in the Integrative Network of Genes, MicroRNAs, Methylations, and Copy Number Variations in Squamous Cell Lung Carcinoma

    PubMed Central

    Cai, Yu-dong

    2015-01-01

    The mechanisms of lung cancer are highly complex. Not only mRNA gene expression but also microRNAs, DNA methylation, and copy number variation (CNV) play roles in tumorigenesis. It is difficult to incorporate so much information into a single model that can comprehensively reflect all these lung cancer mechanisms. In this study, we analyzed the 129 TCGA (The Cancer Genome Atlas) squamous cell lung carcinoma samples with gene expression, microRNA expression, DNA methylation, and CNV data. First, we used variance inflation factor (VIF) regression to build the whole genome integrative network. Then, we isolated the lung cancer subnetwork by identifying the known lung cancer genes and their direct regulators. This subnetwork was refined by the Bayesian method, and the directed regulations among mRNA genes, microRNAs, methylations, and CNVs were obtained. The novel candidate key drivers in this refined subnetwork, such as the methylation of ARHGDIB and HOXD3, microRNA let-7a and miR-31, and the CNV of AGAP2, were identified and analyzed. On three large public available lung cancer datasets, the key drivers ARHGDIB and HOXD3 demonstrated significant associations with the overall survival of lung cancer patients. Our results provide new insights into lung cancer mechanisms. PMID:25802847

  5. 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.

  6. Prognostic Potential and Tumor Growth–Inhibiting Effect of Plasma Advanced Glycation End Products in Non–Small Cell Lung Carcinoma

    PubMed Central

    Bartling, Babett; Hofmann, Hans-Stefan; Sohst, Antonia; Hatzky, Yvonne; Somoza, Veronika; Silber, Rolf-Edgar; Simm, Andreas

    2011-01-01

    The plasma fluorescence related to the standard fluorescence of advanced glycation end products (AGEs) is a simple measurable blood parameter for distinct diseases but its importance in human cancer, including non–small cell lung carcinoma (NSCLC), is unknown. Plasma samples of 70 NSCLC patients who underwent resection surgery of the tumor were analyzed for the distinct AGE-related fluorescence at 370 nm excitation/440 nm emission. In a retrospective study, we tested the prognostic relevance of this AGE-related plasma fluorescence. The effect of circulating AGEs on the NSCLC growth was studied experimentally in vitro and in vivo. NSCLC patients with high (> median) AGE-related plasma fluorescence were characterized by a later reoccurrence of the tumor after curative surgery and a higher survival rate compared with patients with low plasma fluorescence (25% versus 47% 5-y survival, P = 0.011). Treating NSCLC cell spheroids with patients’ plasma showed an inverse correlation between the growth of spheroids in vitro and the individual AGE-related fluorescence of each plasma sample. To confirm the impact of circulating AGEs on the NSCLC progression, we studied the NSCLC growth in mice whose circulating AGE level was elevated by AGE-rich diet. In vivo tumorigenicity assays demonstrated that mice with higher levels of circulating AGEs developed smaller tumors than mice with normal AGE levels. The AGE-related plasma fluorescence has prognostic relevance for NSCLC patients in whom the tumor growth-inhibiting effect of circulating AGEs might play a critical role. PMID:21629968

  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

    2015-01-01

    Carbon-ion radiotherapy (CIRT) holds promise to treat inoperable locally-advanced non-small cell lung carcinoma (NSCLC), a disease poorly controlled by standard chemoradiotherapy using X-rays. Since CIRT is an extremely limited medical resource, selection of NSCLC patients likely to benefit from it is important; however, biological predictors of response to CIRT are ill-defined. The present study investigated the association between the mutational status of EGFR and KRAS, driver genes frequently mutated in NSCLC, and the relative biological effectiveness (RBE) of carbon-ion beams over X-rays. The assessment of 15 NSCLC lines of different EGFR/KRAS mutational status and that of isogenic NSCLC lines expressing wild-type or mutant EGFR revealed that EGFR-mutant NSCLC cells, but not KRAS-mutant cells, show low RBE. This was attributable to (i) the high X-ray sensitivity of EGFR-mutant cells, since EGFR mutation is associated with a defect in non-homologous end joining, a major pathway for DNA double-strand break (DSB) repair, and (ii) the strong cell-killing effect of carbon-ion beams due to poor repair of carbon-ion beam-induced DSBs regardless of EGFR mutation status. These data highlight the potential of EGFR mutation status as a predictor of response to CIRT, i.e., CIRT may show a high therapeutic index in EGFR mutation-negative NSCLC. PMID:26065573

  8. [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. PMID:27426245

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

    PubMed Central

    Yan, Lin; Sundaram, Sneha

    2016-01-01

    Adipose-produced pro-inflammatory cytokines contribute to obesity and cancer. This 2×2 experiment was designed to investigate effects of monocyte chemotactic protein-1 (MCP-1) deficiency on pulmonary metastasis of Lewis lung carcinoma (LLC) in MCP-1 deficient and wild-type mice fed a modified AIN93G diet containing 16% and 45% of energy from corn oil, respectively. The high-fat diet significantly increased the number and size (cross-sectional area and volume) of lung metastases compared to the AIN93G control diet. Deficiency in MCP-1 reduced lung metastases by 37% in high-fat diet-fed mice; it reduced metastatic cross-sectional area by 46% and volume by 69% compared to wild-type mice. Adipose and plasma concentrations of MCP-1 were significantly higher in high-fat diet-fed wild-type mice than in their AIN93G-fed counterparts; they were not detectable in MCP-1 deficient mice regardless of diet. Plasma concentrations of plasminogen activator inhibitor-1, tumor necrosis factor-α, vascular endothelial growth factor and tissue inhibitor of metalloproteinase-1 were significantly higher in MCP-1 deficient mice compared to wild-type mice. We conclude that adipose-produced MCP-1 contributes to high-fat diet-enhanced metastasis. While MCP-1 deficiency reduces metastasis, the elevation of pro-inflammatory cytokines and angiogenic factors in the absence of MCP-1 may support the metastatic development and growth of LLC in MCP-1 deficient mice. PMID:27028862

  10. [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.

  11. 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

  12. Water-soluble extract of Saxifraga stolonifera has anti-tumor effects on Lewis lung carcinoma-bearing mice.

    PubMed

    Liu, Dong; Yang, Ping; Zhang, Yu-Qing

    2016-10-01

    Saxifraga stolonifera is an evergreen and herbaceous plant well known in Korea, Japan and western China, which has great potential applications in gardening and pharmacology. The aim of this study is to evaluate the anti-tumor effects of S. stolonifera extraction on lung tumors of Lewis mice. By the measurement of MS/MS, we found that there were four main bioactive components in methanol extract of S. stolonifera, including gallic acid, norbergenin, protocatechuic acid and bergenin, and the results of quantitative analysis showed that the contents of gallic acid, protocatechuic acid and bergenin in methanol extract of S. stolonifera were 5.150, 1.492, 24.559mg/g, respectively. Animal experiment showed that the mean tumor weight of Lewis lung carcinoma-bearing mice treated with water-soluble extract of S. stolonifera was obviously smaller than model group (cis-DDP), and its inhibition rate was 49.2%. In addition, histopathological evaluation and immunohistochemical assay confirmed the anti-tumor effects of S. stolonifera. Investigation of four haematological parameters revealed that the Lewis mice fed with S. stolonifera showed good resilience in the level of leukocyte, haemoglobin, blood platelets and red blood cell compared with the model group. In addition, RT-PCR suggested that the relative expression of pro-apoptosis gene p53, Sox and Bax was enhanced, while the relative expression of anti-apoptosis gene Bcl2 was diminished in comparison with model group. These results suggested that water-soluble extract of S. stolonifera has anti-tumor effects on Lewis lung tumors. PMID:27575479

  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. FRAGMATIC: A randomised phase III clinical trial investigating the effect of fragmin® added to standard therapy in patients with lung cancer

    PubMed Central

    2009-01-01

    Background Venous thromboembolism (VTE) occurs when blood clots in the leg, pelvic or other deep vein (deep vein thrombosis) with or without transport of the thrombus into the pulmonary arterial circulation (pulmonary embolus). VTE is common in patients with cancer and is increased by surgery, chemotherapy, radiotherapy and disease progression. Low molecular weight heparin (LMWH) is routinely used to treat VTE and some evidence suggests that LMWH may also have an anticancer effect, by reduction in the incidence of metastases. The FRAGMATIC trial will assess the effect of adding dalteparin (FRAGMIN), a type of LMWH, to standard treatment for patients with lung cancer. Methods/Design The study design is a randomised multicentre phase III trial comparing standard treatment and standard treatment plus daily LMWH for 24 weeks in patients with lung cancer. Patients eligible for this study must have histopathological or cytological diagnosis of primary bronchial carcinoma (small cell or non-small cell) within 6 weeks of randomisation, be 18 or older, and must be willing and able to self-administer 5000 IU dalteparin by daily subcutaneous injection or have it administered to themselves or by a carer for 24 weeks. A total of 2200 patients will be recruited from all over the UK over a 3 year period and followed up for a minimum of 1 year after randomisation. Patients will be randomised to one of the two treatment groups in a 1:1 ratio, standard treatment or standard treatment plus dalteparin. The primary outcome measure of the trial is overall survival. The secondary outcome measures include venous thrombotic event (VTE) free survival, serious adverse events (SAEs), metastasis-free survival, toxicity, quality of life (QoL), levels of breathlessness, anxiety and depression, cost effectiveness and cost utility. Trial registration Current Controlled Trials ISRCTN80812769 PMID:19807917

  15. Activation of the BMP-BMPR pathway conferred resistance to EGFR-TKIs in lung squamous cell carcinoma patients with EGFR mutations.

    PubMed

    Wang, Zhijie; Shen, Zhirong; Li, Zhenxiang; Duan, Jianchun; Fu, Shuai; Liu, Zhentao; Bai, Hua; Zhang, Zemin; Zhao, Jun; Wang, Xiaodong; Wang, Jie

    2015-08-11

    The empirical criteria for defining a clinical subtype of lung cancer are gradually transiting from histopathology to genetic variations in driver genes. Targeting these driver mutations, such as sensitizing epidermal growth factor receptor (EGFR) mutations, has dramatically improved the prognosis of advanced non-small cell lung cancer (NSCLC). However, the clinical benefit of molecularly targeted therapy on NSCLC appears to be different between lung adenocarcinomas and squamous cell carcinomas (SqCCs). We report here that the resistance of lung SqCC harboring EGFR mutations to EGFR tyrosine kinase inhibitors (EGFR-TKIs) was due to the activation of BMP-BMPR-Smad1/5-p70S6K. The combined treatment of these tumor cells with EGFR-TKI, together with inhibitors specific to BMPR or downstream mTOR, effectively reversed the resistance to EGFR-TKI. Moreover, blocking the whole PI3K-AKT-mTOR pathway with the PI3K/mTOR dual inhibitor BEZ235 also showed efficacy in treating this subtype of lung SqCC. This study details the empirical basis for a feasible clinical solution for squamous cell carcinomas with EGFR mutations.

  16. Activation of the BMP-BMPR pathway conferred resistance to EGFR-TKIs in lung squamous cell carcinoma patients with EGFR mutations

    PubMed Central

    Wang, Zhijie; Shen, Zhirong; Li, Zhenxiang; Duan, Jianchun; Fu, Shuai; Liu, Zhentao; Bai, Hua; Zhang, Zemin; Zhao, Jun; Wang, Xiaodong; Wang, Jie

    2015-01-01

    The empirical criteria for defining a clinical subtype of lung cancer are gradually transiting from histopathology to genetic variations in driver genes. Targeting these driver mutations, such as sensitizing epidermal growth factor receptor (EGFR) mutations, has dramatically improved the prognosis of advanced non–small cell lung cancer (NSCLC). However, the clinical benefit of molecularly targeted therapy on NSCLC appears to be different between lung adenocarcinomas and squamous cell carcinomas (SqCCs). We report here that the resistance of lung SqCC harboring EGFR mutations to EGFR tyrosine kinase inhibitors (EGFR-TKIs) was due to the activation of BMP-BMPR-Smad1/5-p70S6K. The combined treatment of these tumor cells with EGFR-TKI, together with inhibitors specific to BMPR or downstream mTOR, effectively reversed the resistance to EGFR-TKI. Moreover, blocking the whole PI3K-AKT-mTOR pathway with the PI3K/mTOR dual inhibitor BEZ235 also showed efficacy in treating this subtype of lung SqCC. This study details the empirical basis for a feasible clinical solution for squamous cell carcinomas with EGFR mutations. PMID:26216950

  17. Activation of the BMP-BMPR pathway conferred resistance to EGFR-TKIs in lung squamous cell carcinoma patients with EGFR mutations.

    PubMed

    Wang, Zhijie; Shen, Zhirong; Li, Zhenxiang; Duan, Jianchun; Fu, Shuai; Liu, Zhentao; Bai, Hua; Zhang, Zemin; Zhao, Jun; Wang, Xiaodong; Wang, Jie

    2015-08-11

    The empirical criteria for defining a clinical subtype of lung cancer are gradually transiting from histopathology to genetic variations in driver genes. Targeting these driver mutations, such as sensitizing epidermal growth factor receptor (EGFR) mutations, has dramatically improved the prognosis of advanced non-small cell lung cancer (NSCLC). However, the clinical benefit of molecularly targeted therapy on NSCLC appears to be different between lung adenocarcinomas and squamous cell carcinomas (SqCCs). We report here that the resistance of lung SqCC harboring EGFR mutations to EGFR tyrosine kinase inhibitors (EGFR-TKIs) was due to the activation of BMP-BMPR-Smad1/5-p70S6K. The combined treatment of these tumor cells with EGFR-TKI, together with inhibitors specific to BMPR or downstream mTOR, effectively reversed the resistance to EGFR-TKI. Moreover, blocking the whole PI3K-AKT-mTOR pathway with the PI3K/mTOR dual inhibitor BEZ235 also showed efficacy in treating this subtype of lung SqCC. This study details the empirical basis for a feasible clinical solution for squamous cell carcinomas with EGFR mutations. PMID:26216950

  18. Dramatic response to anti-PD-1 therapy in a patient of squamous cell carcinoma of thymus with multiple lung metastases.

    PubMed

    Yang, Yan; Ding, Liren; Wang, Pingli

    2016-07-01

    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

  19. 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.

  20. 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.

  1. [Disease-free survival in a patient with squamous cell lung carcinoma following complete response with the combination chemotherapy of cisplatin and etoposide].

    PubMed

    Taniwaki, M; Kakusui, M; Imoto, M; Takashima, T; Misawa, S; Kashima, K

    1993-05-01

    Disease-free survival is reported in a patient with non-small cell lung carcinoma successfully treated with the combination chemotherapy of cisplatin and etoposide (CDDP-ETOP). An 80-year-old woman was diagnosed as having squamous cell carcinoma of the lung with bone metastasis. Chest X-ray showed a tumor (64 x 68 mm in size) in the S1/4 segment of the right lobe, and CT scan revealed no apparent metastasis of hilar lymphnode. In March 1989, the patient achieved a complete response (CR) after two courses of CDDP-ETOP therapy, followed by ETOP(100mg) every two weeks and daily UFT (400 mg) for 10 months. Subsequently, a single course of CDDP-ETOP was administered as a consolidation therapy. The patient is alive with no evidence of recurrent disease for 3 years and half after achieving CR.

  2. 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.

  3. Systemic treatments for brain metastases from breast cancer, non-small cell lung cancer, melanoma and renal cell carcinoma: an overview of the literature.

    PubMed

    Lombardi, Giuseppe; Di Stefano, Anna Luisa; Farina, Patrizia; Zagonel, Vittorina; Tabouret, Emeline

    2014-09-01

    The frequency of metastatic brain tumors has increased over recent years; the primary tumors most involved are breast cancer, lung cancer, melanoma and renal cell carcinoma. While radiation therapy and surgery remain the mainstay treatment in selected patients, new molecular drugs have been developed for brain metastases. Studies so far report interesting results. This review focuses on systemic cytotoxic drugs and, in particular, on new targeted therapies and their clinically relevant activities in brain metastases from solid tumors in adults.

  4. Assessment of DNA damage of Lewis lung carcinoma cells irradiated by carbon ions and X-rays using alkaline comet assay

    NASA Astrophysics Data System (ADS)

    Li, Ping; Zhou, Li-Bin; Jin, Xiao-Dong; He, Jing; Dai, Zhong-Ying; Zhou, Guang-Ming; Gao, Qing-Xiang; Li, Sha; Li, Qiang

    2008-01-01

    DNA damage and cell reproductive death determined by alkaline comet and clonogenic survival assays were examined in Lewis lung carcinoma cells after exposure to 89.63 MeV/u carbon ion and 6 MV X-ray irradiations, respectively. Based on the survival data, Lewis lung carcinoma cells were verified to be more radiosensitive to the carbon ion beam than to the X-ray irradiation. The relative biological effectiveness (RBE) value, which was up to 1.77 at 10% survival level, showed that the DNA damage induced by the high-LET carbon ion beam was more remarkable than that induced by the low-LET X-ray irradiation. The dose response curves of “Tail DNA (%)” (TD) and “Olive tail moment” (OTM) for the carbon ion irradiation showed saturation beyond about 8 Gy. This behavior was not found in the X-ray curves. Additionally, the carbon ion beam produced a lower survival fraction at 2 Gy (SF2) value and a higher initial Olive tail moment 2 Gy (OTM2) than those for the X-ray irradiation. These results suggest that carbon ion beams having high-LET values produced more severe cell reproductive death and DNA damage in Lewis lung carcinoma cells in comparison with X-rays and comet assay might be an effective predictive test even combining with clonogenic assay to assess cellular radiosensitivity.

  5. Erlotinib-associated interstitial lung disease in advanced pancreatic carcinoma: a case report and literature review.

    PubMed

    Macerelli, Marianna; Mazzer, Micol; Foltran, Luisa; Cardellino, Giovanni Gerardo; Aprile, Giuseppe

    2015-07-24

    The combination of erlotinib and gemcitabine is a recognized option for patients with metastatic pancreatic cancer whose common adverse events such as skin rash, diarrhea, or fatigue are usually easily manageable. Interstitial lung disease (ILD) is a life-threatening toxicity reported in patients with non-small-cell lung cancers treated with epidermal growth factor receptor-tyrosine kinase inhibitors or gemcitabine. This side effect is extremely rare in patients with pancreatic cancer. We report fatal treatment-related ILD that occurred in a 67-year-old patient with metastatic pancreatic cancer. Risk factors and pathophysiology of ILD need further investigation but caution is highly recommended for patients with an underlying pulmonary disease when using erlotinib in monotherapy or combination therapy.

  6. 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

  7. Trace element profiles in murine Lewis lung carcinoma by radioisotope-induced X-ray fluorescence.

    PubMed Central

    Frank, A. S.; Schauble, M. K.; Preiss, I. L.

    1986-01-01

    Trace element profiles of various body tissues and tumor were established during growth of the Lewis lung tumor (LLT) with the use of radioisotope-induced X-ray fluorescence (RIXRF) analysis. The LLT, a highly malignant experimental murine tumor, resembles its human counterpart, has a well-defined life cycle, and kills its host in 30 days. When compared with normal controls, Zn, Br, and Rb levels in lung, liver, and skeletal muscle and Zn and Sr levels in bone from tumor-bearing mice exhibited large fluctuations at critical points in the tumor life cycle. In addition, the 24-day primary tumor trace element profile resembled that of its tissue of origin, normal lung, and was quite different from other normal tissues studied. These findings indicate that trace element profiles may help in the diagnosis, staging, and monitoring of disease. RIXRF is an excellent technique for this purpose because it is sensitive and relatively nondestructive of samples and has multielement capabilities. Images Figure 1 p423-a PMID:3953767

  8. Recurrent inactivating mutations of ARID2 in non-small cell lung carcinoma.

    PubMed

    Manceau, Gilles; Letouzé, Eric; Guichard, Cécile; Didelot, Audrey; Cazes, Aurelie; Corté, Hélène; Fabre, Elizabeth; Pallier, Karine; Imbeaud, Sandrine; Le Pimpec-Barthes, Françoise; Zucman-Rossi, Jessica; Laurent-Puig, Pierre; Blons, Hélène

    2013-05-01

    In eukaryotic cells, DNA is packaged into chromatin and this compact storage in the nucleus promotes transcriptional repression of genes. Chromatin remodeling complexes such as the SWI/SNF complex are involved in making DNA accessible to transcription factors and thereby are implicated in the regulation of gene expression. Mutations and altered expression of chromatin remodeling complex genes have been described in cancer cells. Indeed, non-small cell lung cancer cell lines have been shown to harbor mutations in SMARCA4 (BRG1), a member of the SWI/SNF complex, but evidence has been less clear in primary tumors. Recently, inactivating mutations in AT-rich interaction domain 2 (ARID2) were found in liver cancer related to HCV infection and in melanoma. Here, we explored, using a genome-wide strategy and subsequent sequencing of targeted genes, whether chromatin remodeling is implicated in primary lung adenocarcinoma. Two genes were individualized from the genome screening as homozygously deleted in a set of samples: JARID2 and ARID2. Subsequent analysis of the entire coding sequences showed that ARID2 loss-of-function mutations were found in 5% of nonsmall cell lung cancers, thereby constituting one of the most frequently mutated genes in this cancer type after TP53, KRAS, EGFR, CDKN2A and STK11.

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

    PubMed

    Bar, Jair; Hasim, Mohamed S; Baghai, Tabassom; Niknejad, Nima; Perkins, Theodore J; Stewart, David J; Sekhon, Harmanjatinder S; Villeneuve, Patrick J; Dimitroulakos, Jim

    2016-09-01

    Non-small cell lung carcinoma (NSCLC) is the most common cause of cancer deaths, with platin-based combination chemotherapy the most efficacious therapies. Gains in overall survival are modest, highlighting the need for novel therapeutic approaches including the development of next-generation platin combination regimens. The goal of this study was to identify novel regulators of platin-induced cytotoxicity as potential therapeutic targets to further enhance platin cytotoxicity. Employing RNA-seq transcriptome analysis comparing two parental NSCLC cell lines Calu6 and H23 to their cisplatin-resistant sublines, Calu6cisR1 and H23cisR1, activating transcription factor 3 (ATF3) was robustly induced in cisplatin-treated parental sensitive cell lines but not their resistant sublines, and in three of six tumors evaluated, but not in their corresponding normal adjacent lung tissue (0/6). Cisplatin-induced JNK activation was a key regulator of this ATF3 induction. Interestingly, in both resistant sublines, this JNK induction was abrogated, and the expression of an activated JNK construct in these cells enhanced both cisplatin-induced cytotoxicity and ATF3 induction. An FDA-approved drug compound screen was employed to identify enhancers of cisplatin cytotoxicity that were dependent on ATF3 gene expression. Vorinostat, a histone deacetylase inhibitor, was identified in this screen and demonstrated synergistic cytotoxicity with cisplatin in both the parental Calu6 and H23 cell lines and importantly in their resistant sublines as well that was dependent on ATF3 expression. Thus, we have identified ATF3 as an important regulator of cisplatin cytotoxicity and that ATF3 inducers in combination with platins are a potential novel therapeutic approach for NSCLC. PMID:27659012

  10. Profile of Ventana ALK (D5F3) companion diagnostic assay for non-small-cell lung carcinomas.

    PubMed

    Conde, Esther; Hernandez, Susana; Prieto, Mario; Martinez, Rebeca; Lopez-Rios, Fernando

    2016-06-01

    The development of several ALK inhibitors means that the importance of accurately identifying ALK-positive lung cancer has never been greater. Therefore, it is crucial that ALK testing assays become more standardized. The aim of this review is to comment on the recently FDA-approved VENTANA ALK (D5F3) Companion Diagnostic (CDx) Assay. This kit provides high sensitivity and specificity for the detection of ALK rearrangements and seamless integration into the laboratory workflow, with a fully automated analytical phase and fast interpretation. The use of controls increases the sensitivity and specificity and a dichotomous scoring approach enhances reproducibility.

  11. Down-Regulation of Canonical and Up-Regulation of Non-Canonical Wnt Signalling in the Carcinogenic Process of Squamous Cell Lung Carcinoma

    PubMed Central

    Weich, Alexander; Kiss, Edit; Barko, Szilvia; Kovacs, Tamas; Avdicevic, Monika; D’Souza, Vijay K.; Rapp, Judit; Kvell, Krisztian; Jakab, Laszlo; Nyitrai, Miklos; Molnar, Tamas F.; Thickett, David R.; Laszlo, Terezia; Pongracz, Judit E.

    2013-01-01

    The majority of lung cancers (LC) belong to the non-small cell lung carcinoma (NSCLC) type. The two main NSCLC sub-types, namely adenocarcinoma (AC) and squamous cell carcinoma (SCC), respond differently to therapy. Whereas the link between cigarette smoke and lung cancer risk is well established, the relevance of non-canonical Wnt pathway up-regulation detected in SCC remains poorly understood. The present study was undertaken to investigate further the molecular events in canonical and non-canonical Wnt signalling during SCC development. A total of 20 SCC and AC samples with matched non-cancerous controls were obtained after surgery. TaqMan array analysis confirmed up-regulation of non-canonical Wnt5a and Wnt11 and identified down-regulation of canonical Wnt signalling in SCC samples. The molecular changes were tested in primary small airway epithelial cells (SAEC) and various lung cancer cell lines (e.g. A549, H157, etc). Our studies identified Wnt11 and Wnt5a as regulators of cadherin expression and potentiated relocation of β-catenin to the nucleus as an important step in decreased cellular adhesion. The presented data identifies additional details in the regulation of SCC that can aid identification of therapeutic drug targets in the future. PMID:23505429

  12. Long-term survival of a patient with small cell carcinoma of the stomach with metachronous lung metastases treated by multimodal therapy: a case report.

    PubMed

    Aoyagi, Keishiro; Kizaki, Junya; Isobe, Taro; Akagi, Yoshito

    2015-12-01

    A 69-year-old man was referred to our institution for treatment of gastric cancer. Type 2 gastric cancer was found on the anterior wall of the lower body of the stomach.The patient underwent distal gastrectomy, D2 lymph node dissection, and Roux-en-Y reconstruction with curative resection. The tumor was diagnosed as a small cell carcinoma of the stomach. Recurrence occurred in the lung after surgery. The patient underwent several chemoradiation therapy regimens, including cisplatin + irinotecan + radiation, S-1 + paclitaxel, amrubicin, carboplatin + etoposide, nogitecan, and docetaxel for lung metastases and radiation for brain and bone metastases for 43 months. He finally died of brain metastases 74 months after surgery (47 months after recognition of the lung metastases). Long continuous multimodal treatment including surgery, regimens for small cell lung cancer, S-1, taxanes, and radiation was thought to prolong the survival of this man with small cell carcinoma of the stomach. PMID:26943449

  13. [Current status of EGFR/ErbB inhibitors in non-small cell lung carcinoma].

    PubMed

    Álvarez-Fernández, Carlos; Esteban-González, Emilio

    2016-04-01

    In the last 10 years, there has been a major change in the treatment of lung cancer (LC). The discovery of activating mutations in the epidermal growth factor receptor (EGFR) in some histological subtypes of LC and its sensitivity to tyrosine kinase inhibitors (TKI) has represented a substantial advance in the treatment of this entity. Until then, the only available option to treat this type of tumour was based on chemotherapy, with a small but significant benefit in terms of survival and quality of life. The arrival of new agents that act against activating EGFR mutations gave rise to the era of precision medicine with targeted therapies able to act on the origin of the tumour, thus providing a therapeutic benefit while minimizing adverse effects and delaying administration of chemotherapy. In addition, this has produced a change in the diagnostic paradigm of lung cancer (as well as in that of all tumours), with a shift from a purely histological diagnosis to a classification of tumours based on their mutational characteristics. This shift has been made possible by the development of technologies allowing complex DNA analysis. Together with the efforts of researchers from all over the world, these techniques allow continued discovery of genetic alterations that could be the target of new drugs as well as definition of the mechanisms of activity and resistance to treatments. This extraordinary development of targeted therapies cannot change the fact that metastatic lung cancer continues to be an incurable disease and, at the present time, only a few patients will benefit from targeted therapies. Ongoing research will shed new light on the molecular alterations that give rise to LC and will provide new treatment alternatives for this disease. PMID:27426241

  14. [Current status of EGFR/ErbB inhibitors in non-small cell lung carcinoma].

    PubMed

    Álvarez-Fernández, Carlos; Esteban-González, Emilio

    2016-04-01

    In the last 10 years, there has been a major change in the treatment of lung cancer (LC). The discovery of activating mutations in the epidermal growth factor receptor (EGFR) in some histological subtypes of LC and its sensitivity to tyrosine kinase inhibitors (TKI) has represented a substantial advance in the treatment of this entity. Until then, the only available option to treat this type of tumour was based on chemotherapy, with a small but significant benefit in terms of survival and quality of life. The arrival of new agents that act against activating EGFR mutations gave rise to the era of precision medicine with targeted therapies able to act on the origin of the tumour, thus providing a therapeutic benefit while minimizing adverse effects and delaying administration of chemotherapy. In addition, this has produced a change in the diagnostic paradigm of lung cancer (as well as in that of all tumours), with a shift from a purely histological diagnosis to a classification of tumours based on their mutational characteristics. This shift has been made possible by the development of technologies allowing complex DNA analysis. Together with the efforts of researchers from all over the world, these techniques allow continued discovery of genetic alterations that could be the target of new drugs as well as definition of the mechanisms of activity and resistance to treatments. This extraordinary development of targeted therapies cannot change the fact that metastatic lung cancer continues to be an incurable disease and, at the present time, only a few patients will benefit from targeted therapies. Ongoing research will shed new light on the molecular alterations that give rise to LC and will provide new treatment alternatives for this disease.

  15. Disseminated Skeletal Muscle and Cardiac Metastasis from Squamous Cell Carcinoma of the Lung Detected with FDG and FLT PET/CT

    PubMed Central

    Jain, Tarun Kumar; Rayamajhi, Sampanna Jung; Basher, Rajender Kumar; Gupta, Dheeraj; Maturu, Venkata Nagarjuna; Mittal, Bhagwant Rai

    2016-01-01

    Lung cancer is one of the leading cancers all over the world. Positron emission tomography (PET) using 18F fluorodeoxyglucose (18F FDG) is useful for staging of the disease and decide the appropriate management. 3’-deoxy-3’-18 F-fluorothymidine (18F FLT) is a tracer being extensively evaluated currently and is said to represent tumor proliferation. Common sites of metastases from lung cancer include adrenal glands, bone, and brain. Muscle metastasis and cardiac metastasis are uncommon findings. We report a case of squamous cell carcinoma of the lung with metastases to multiple skeletal muscles and myocardium detected with both FDG and FLT PET/computed tomography (CT). PMID:27651747

  16. [Long-term complete response of multiple lung metastases from renal cell carcinoma induced by combination therapy with interferon alpha and UFT: a case report].

    PubMed

    Terachi, T; Okada, Y; Takeuchi, H; Yoshida, O

    1993-04-01

    We report a case of long-term complete response of multiple lung metastases of renal cell carcinoma (RCC) by the combination therapy with interferon alpha (IFN alpha) and UFT. A 38 year-old man having left RCC with lung metastases underwent radical left nephrectomy and extended lymph node dissection, the pathological stage being pT2N2. Although metastatic lung tumors increased in size and number against intravenously admitted interferon gamma (IFN gamma) therapy after the surgery, they completely disappeared following the subsequent combination therapy with intramuscularly admitted interferon alpha (IFN alpha) and oral intake of UFT in about 2 years. The patient has been disease-free for 5 years after cessation of the treatment. Combination therapy with IFN alpha and UFT might be more effective on metastases of RCC than single use of IFN alpha or IFN gamma.

  17. Clear-cell carcinoma of the lung metastatic to the hamate: a case report.

    PubMed

    Nissenbaum, M; Kutz, J E; Lister, G D

    1978-01-01

    Metastatic lesions of the hand are uncommon. A report of a solitary metastasis to the hamate seems not to have appeared previously in the literature. A 46-year-old factory worker presented a rare tumor, clear-cell carcinom of the lung, metastasizing to an unusual location, the hamate. The symptoms simulated sympathetic dystrophy and diagnosis was delayed because of the late appearance of radiographic changes over 6 months after symptoms first appeared. Early bone scanning in patients with chronic pain may provide useful information prior to the appearance of X-ray changes.

  18. Diffuse cystic lung disease due to pulmonary metastasis of colorectal carcinoma

    PubMed Central

    Fielli, Mariano; Avila, Fabio; Saino, Agustina; Seimah, Deborah; Fernández Casares, Marcelo

    2016-01-01

    The diffuse cystic lung diseases (DCLDs) are a pathophysiologically heterogeneous processes characterized by the presence of multiple thin-walled, air-filled spaces within the pulmonary parenchyma. The most common causes of DCLD are lymphangioleiomyomatosis (LAM) and pulmonary Langerhans cell histiocytosis (PLCH). DCLD develops rarely as a result of malignancy, typically secondary to metastases from peripheral sarcomas and mesenchymal tumors. DCLD have also been reported in a variety of other metastatic disease such as adenocarcinoma. Our case describes a patient with DCLD as a result of metastatic colorectal adenocarcinoma. PMID:27222791

  19. Whole Exome Sequencing Identifies Frequent Somatic Mutations in Cell-Cell Adhesion Genes in Chinese Patients with Lung Squamous Cell Carcinoma

    PubMed Central

    Li, Chenguang; Gao, Zhibo; Li, Fei; Li, Xiangchun; Sun, Yihua; Wang, Mengyun; Li, Dan; Wang, Rui; Li, Fuming; Fang, Rong; Pan, Yunjian; Luo, Xiaoyang; He, Jing; Zheng, Liangtao; Xia, Jufeng; Qiu, Lixin; He, Jun; Ye, Ting; Zhang, Ruoxin; He, Minghui; Zhu, Meiling; Hu, Haichuan; Shi, Tingyan; Zhou, Xiaoyan; Sun, Menghong; Tian, Shilin; Zhou, Yong; Wang, Qiaoxiu; Chen, Longyun; Yin, Guangliang; Lu, Jingya; Wu, Renhua; Guo, Guangwu; Li, Yingrui; Hu, Xueda; Li, Lin; Asan, A; Wang, Qin; Yin, Ye; Feng, Qiang; Wang, Bin; Wang, Hang; Wang, Mingbang; Yang, Xiaonan; Zhang, Xiuqing; Yang, Huanming; Jin, Li; Wang, Cun-Yu; Ji, Hongbin; Chen, Haiquan; Wang, Jun; Wei, Qingyi

    2015-01-01

    Lung squamous cell carcinoma (SQCC) accounts for about 30% of all lung cancer cases. Understanding of mutational landscape for this subtype of lung cancer in Chinese patients is currently limited. We performed whole exome sequencing in samples from 100 patients with lung SQCCs to search for somatic mutations and the subsequent target capture sequencing in another 98 samples for validation. We identified 20 significantly mutated genes, including TP53, CDH10, NFE2L2 and PTEN. Pathways with frequently mutated genes included those of cell-cell adhesion/Wnt/Hippo in 76%, oxidative stress response in 21%, and phosphatidylinositol-3-OH kinase in 36% of the tested tumor samples. Mutations of Chromatin regulatory factor genes were identified at a lower frequency. In functional assays, we observed that knockdown of CDH10 promoted cell proliferation, soft-agar colony formation, cell migration and cell invasion, and overexpression of CDH10 inhibited cell proliferation. This mutational landscape of lung SQCC in Chinese patients improves our current understanding of lung carcinogenesis, early diagnosis and personalized therapy. PMID:26503331

  20. Identification and Characterization of Epstein-Barr Virus Genomes in Lung Carcinoma Biopsy Samples by Next-Generation Sequencing Technology

    PubMed Central

    Wang, Shanshan; Xiong, Hongchao; Yan, Shi; Wu, Nan; Lu, Zheming

    2016-01-01

    Epstein-Barr virus (EBV) has been detected in the tumor cells of several cancers, including some cases of lung carcinoma (LC). However, the genomic characteristics and diversity of EBV strains associated with LC are poorly understood. In this study, we sequenced the EBV genomes isolated from four primary LC tumor biopsy samples, designated LC1 to LC4. Comparative analysis demonstrated that LC strains were more closely related to GD1 strain. Compared to GD1 reference genome, a total of 520 variations in all, including 498 substitutions, 12 insertions, and 10 deletions were found. Latent genes were found to harbor the most numbers of nonsynonymous mutations. Phylogenetic analysis showed that all LC strains were closely related to Asian EBV strains, whereas different from African/American strains. LC2 genome was distinct from the other three LC genomes, suggesting at least two parental lineages of EBV among the LC genomes may exist. All LC strains could be classified as China 1 and V-val subtype according to the amino acid sequence of LMP1 and EBNA1, respectively. In conclusion, our results showed the genomic diversity among EBV genomes isolated from LC, which might facilitate to uncover the previously unknown variations of pathogenic significance. PMID:27189712

  1. MicroRNA-588 suppresses tumor cell migration and invasion by targeting GRN in lung squamous cell carcinoma

    PubMed Central

    Qian, Li; Lin, Longlong; Du, Yufeng; Hao, Xiaoyan; Zhao, Yuze; Liu, Xuejun

    2016-01-01

    MicroRNAs (miRNAs) have been demonstrated to be critical in regulating tumor development and progression. The present study investigated the expression of miR-588 using reverse transcription-quantitative polymerase chain reaction analysis in 85 cases of lung squamous cell carcinoma (SCC), and observed the correlation between the expression of miR-588 with clinical pathologic features. The results indicated that the expression of miR-588 was predominantly lower in the tumor samples, compared with non-tumorous samples, and was negatively associated with tumor stages and lymph node invasion. The present study also examined the significance of the expression of miR-588 in SCC using gain- and loss-of-function analyses. It was found that miR-588 inhibited tumor cell migration and invasion. In addition, it was revealed that the overexpression of miR-588 in SCC cells reduced the mRNA and protein levels of progranulin (GRN), whereas miR-588 silencing increased the expression of GRN. A luciferase activity assay showed that miR-588 was able to directly bind to the 3′untranslated region of GRN and regulate its expression. Furthermore, it was found that the expression of GRN was inversely correlated with the expression of miR-588 in 85 paired SCC samples. These results indicated that GRN was involved in the miR-588-mediated suppressive functions in the progression of SCC. PMID:27571908

  2. Isogambogenic acid induces apoptosis-independent autophagic cell death in human non-small-cell lung carcinoma cells.

    PubMed

    Yang, Jianhong; Zhou, Yongzhao; Cheng, Xia; Fan, Yi; He, Shichao; Li, Shucai; Ye, Haoyu; Xie, Caifeng; Wu, Wenshuang; Li, Chunyan; Pei, Heying; Li, Luyuan; Wei, Zhe; Peng, Aihua; Wei, Yuquan; Li, Weimin; Chen, Lijuan

    2015-01-09

    To overcome drug resistance caused by apoptosis deficiency in patients with non-small cell lung carcinoma (NSCLC), there is a need to identify other means of triggering apoptosis-independent cancer cell death. We are the first to report that isogambogenic acid (iso-GNA) can induce apoptosis-independent autophagic cell death in human NSCLC cells. Several features of the iso-GNA-treated NSCLC cells indicated that iso-GNA induced autophagic cell death. First, there was no evidence of apoptosis or cleaved caspase 3 accumulation and activation. Second, iso-GNA treatment induced the formation of autophagic vacuoles, increased LC3 conversion, caused the appearance of autophagosomes and increased the expression of autophagy-related proteins. These findings provide evidence that iso-GNA induces autophagy in NSCLC cells. Third, iso-GNA-induced cell death was inhibited by autophagic inhibitors or by selective ablation of Atg7 and Beclin 1 genes. Furthermore, the mTOR inhibitor rapamycin increased iso-GNA-induced cell death by enhancing autophagy. Finally, a xenograft model provided additional evidence that iso-GNA exhibited anticancer effect through inducing autophagy-dependent cell death in NSCLC cells. Taken together, our results demonstrated that iso-GNA exhibited an anticancer effect by inducing autophagy-dependent cell death in NSCLC cells, which may be an effective chemotherapeutic agent that can be used against NSCLC in a clinical setting.

  3. Isogambogenic acid induces apoptosis-independent autophagic cell death in human non-small-cell lung carcinoma cells

    PubMed Central

    Yang, Jianhong; Zhou, Yongzhao; Cheng, Xia; Fan, Yi; He, Shichao; Li, Shucai; Ye, Haoyu; Xie, Caifeng; Wu, Wenshuang; Li, Chunyan; Pei, Heying; Li, Luyuan; Wei, Zhe; Peng, Aihua; Wei, Yuquan; Li, Weimin; Chen, Lijuan

    2015-01-01

    To overcome drug resistance caused by apoptosis deficiency in patients with non-small cell lung carcinoma (NSCLC), there is a need to identify other means of triggering apoptosis-independent cancer cell death. We are the first to report that isogambogenic acid (iso-GNA) can induce apoptosis-independent autophagic cell death in human NSCLC cells. Several features of the iso-GNA-treated NSCLC cells indicated that iso-GNA induced autophagic cell death. First, there was no evidence of apoptosis or cleaved caspase 3 accumulation and activation. Second, iso-GNA treatment induced the formation of autophagic vacuoles, increased LC3 conversion, caused the appearance of autophagosomes and increased the expression of autophagy-related proteins. These findings provide evidence that iso-GNA induces autophagy in NSCLC cells. Third, iso-GNA-induced cell death was inhibited by autophagic inhibitors or by selective ablation of Atg7 and Beclin 1 genes. Furthermore, the mTOR inhibitor rapamycin increased iso-GNA-induced cell death by enhancing autophagy. Finally, a xenograft model provided additional evidence that iso-GNA exhibited anticancer effect through inducing autophagy-dependent cell death in NSCLC cells. Taken together, our results demonstrated that iso-GNA exhibited an anticancer effect by inducing autophagy-dependent cell death in NSCLC cells, which may be an effective chemotherapeutic agent that can be used against NSCLC in a clinical setting. PMID:25571970

  4. Staurosporine and extracellular matrix proteins mediate the conversion of small cell lung carcinoma cells into a neuron-like phenotype.

    PubMed

    Murmann, Tamara; Carrillo-García, Carmen; Veit, Nadine; Courts, Cornelius; Glassmann, Alexander; Janzen, Viktor; Madea, Burkhard; Reinartz, Markus; Harzen, Anne; Nowak, Michael; Perner, Sven; Winter, Jochen; Probstmeier, Rainer

    2014-01-01

    Small cell lung carcinomas (SCLCs) represent highly aggressive tumors with an overall five-year survival rate in the range of 5 to 10%. Here, we show that four out of five SCLC cell lines reversibly develop a neuron-like phenotype on extracellular matrix constituents such as fibronectin, laminin or thrombospondin upon staurosporine treatment in an RGD/integrin-mediated manner. Neurite-like processes extend rapidly with an average speed of 10 µm per hour. Depending on the cell line, staurosporine treatment affects either cell cycle arrest in G2/M phase or induction of polyploidy. Neuron-like conversion, although not accompanied by alterations in the expression pattern of a panel of neuroendocrine genes, leads to changes in protein expression as determined by two-dimensional gel electrophoresis. It is likely that SCLC cells already harbour the complete molecular repertoire to convert into a neuron-like phenotype. More extensive studies are needed to evaluate whether the conversion potential of SCLC cells is suitable for therapeutic interventions.

  5. Mesenchymal Stem Cells Shed Amphiregulin at the Surface of Lung Carcinoma Cells in a Juxtacrine Manner12

    PubMed Central

    Carnet, Oriane; Lecomte, Julie; Masset, Anne; Primac, Irina; Durré, Tania; Maertens, Ludovic; Detry, Benoit; Blacher, Silvia; Gilles, Christine; Péqueux, Christel; Paupert, Jenny; Foidart, Jean-Michel; Jerusalem, Guy; Cataldo, Didier; Noel, Agnès

    2015-01-01

    Solid tumors comprise cancer cells and different supportive stromal cells, including mesenchymal stem cells (MSCs), which have recently been shown to enhance tumor growth and metastasis. We provide new mechanistic insights into how bone marrow (BM)–derived MSCs co-injected with Lewis lung carcinoma cells promote tumor growth and metastasis in mice. The proinvasive effect of BM-MSCs exerted on tumor cells relies on an unprecedented juxtacrine action of BM-MSC, leading to the trans-shedding of amphiregulin (AREG) from the tumor cell membrane by tumor necrosis factor-α–converting enzyme carried by the BM-MSC plasma membrane. The released soluble AREG activates cancer cells and promotes their invasiveness. This novel concept is supported by the exploitation of different 2D and 3D culture systems and by pharmacological approaches using a tumor necrosis factor-α–converting enzyme inhibitor and AREG-blocking antibodies. Altogether, we here assign a new function to BM-MSC in tumor progression and establish an uncovered link between AREG and BM-MSC. PMID:26297433

  6. Synergistic antitumor effects of 131I-LC-1 IgM and IL-12 vaccine on Lewis lung carcinoma.

    PubMed

    Yin, Xiao Ling; Yan, Xuexian; Wen, Ming; Peng, Zhi Ping; Li, Shao Lin

    2010-03-01

    This study was designed to determine the antitumor effects of iodine-131 labeled monoclonal antibody LC-1 ((131)I-LC-1), interleukin-12 (IL-12) vaccine, or the combination of both on C57BL/6 mice bearing Lewis lung carcinoma (LLC) tumors. Tumor-bearing mice models were randomly divided into 4 groups that were respectively injected intratumorally with phosphate buffered solution (PBS), IL-12 vaccine gene therapy (GT), (131)I-LC-1 radioimmuno-therapy (RIT), or GT+RIT. Tumor volumes were measured before and after treatment. ELISA and RT-PCR determined the expression of IL-l2. LC-1 monoclonal antibody (Mab) was labeled with Na(131)I. Cytolytic T lymphocyte (CTL) activity assay, Natural Killer cell (NK) activity assay and apoptosis analysis were performed. Intratumoral (131)I-LC-1 injection leads to higher delivery of the antibody to the tumor. Tumor apoptosis occurred in the GT, RIT and GT+RIT groups. Tumor growth was inhibited in the GT, RIT and GT+RIT groups. Compared with other groups, the combination of GT+RIT up-regulated the expression of IL-l2 gene and inhibited the tumor growth more effectively than either GT or RIT alone (p<0.05). These results suggest that GT+RIT have the synergistic antitumor effects on tumor-bearing mice.

  7. Characterization of a small-cell-lung-carcinoma cell line from a patient with cancer-associated retinopathy.

    PubMed

    Yamaji, Y; Matsubara, S; Yamadori, I; Sato, M; Fujita, T; Fujita, J; Takahara, J

    1996-03-01

    We examined the biologic properties of a small-cell-lung-carcinoma (SCLC) cell line (designated MN-1112) established from a patient with SCLC who showed paraneoplastic retinopathy syndrome. Morphologic and immunocytochemical analyses showed that MN-1112 cells possess features of the classic type of SCLC. MN-1112 cells grew in suspension forming relatively large clumps of cells with a doubling time of 72 hr. By light-microscope examination, the cells were relatively small and had scanty cytoplasm. The cells produced NSE, ACTH and CK (BB isozyme); they also expressed recoverin, a novel photoreceptor protein, detected by Northern-blot and Western-immunoblot analysis using human-recoverin-specific DNA probe and anti-bovine-recoverin polyclonal antibody. This report shows that human recoverin is expressed in cultured SCLC cells. Our results support the hypothesis that, in cancer-associated retinopathy (CAR) patients, auto-immune antibody targeting for ectopic recoverin in SCLC is initially produced and cross-reacts with the retinal protein, resulting in the retinal degeneration that occurs in CAR patients.

  8. Palliative radiotherapy for inoperable carcinoma of the lung: final report of a RTOG multi-institutional trial

    SciTech Connect

    Simpson, J.R.; Francis, M.E.; Perez-Tamayo, R.; Marks, R.D.; Rao, D.V.

    1985-04-01

    Between June 1973 and February 1979, 409 patients with inoperable advanced non-oat cell carcinoma of the lung were randomized on RTOG protocol 73-02. Three treatment arms were evaluated: 40 Gy split course, 30 Gy continuous course, and 40 Gy continuous course. Patients were also randomized to receive cytoxan or no further therapy following irradiation. Three hundred sixteen patients were evaluable. Palliation of symptoms was achieved in 60% with 1/4 of the patients becoming symptom-free. Complete regression of local and regional tumor was produced in 15% and partial regression in 26%. There is no significant difference between the treatment arms in these objective response rates. Median survival times were approximately 6 months. No significant benefit was demonstrated by the adjuvant use of Cytoxan. Although the number of complete responses produced was relatively small, patients achieving a complete response had a significantly longer median survival than the remaining patients, i.e., 14.5 months versus 6 months. Significant toxicity occurred in fewer than 6% of patients. Radiation pneumonitis counted for the majority of these adverse reactions. Toxicity occurred somewhat more often in the group treated with 40 Gy split course therapy. Implications for further studies are discussed.

  9. Chromogenic in situ hybridization to detect EGFR gene copy number in cell blocks from fine-needle aspirates of non small cell lung carcinomas and lung metastases from colo-rectal cancer

    PubMed Central

    2010-01-01

    Background Several studies demonstrated that epidermal growth factor receptor (EGFR) gene copy number (GCN) correlates to the response to tyrosine kinase inhibitors in non small cell lung cancer (NSCLC) and to anti-EGFR monoclonal antibodies (MoAbs) in metastatic colorectal cancer (CRC). In the presence of lung nodules, cytology is often the only possible diagnostic approach. Chromogenic in situ hybridization (CISH) is an alternative technique to fluorescence in situ hybridization (FISH), but its feasibility in detecting EGFR GCN in cell blocks from fine-needle aspiration cytology (FNAC) of lung nodules has not yet been established. Methods We evaluated the feasibility of CISH on 33 FNAC from 20 primary NSCLC (5 squamous carcinomas, 8 large cell carcinomas and 7 adenocarcinomas) and 13 lung metastases from CRC. Results Of the 33 FNAC analyzed by CISH, 27 (82%) presented a balanced increase in EGFR gene and chromosome 7 number: 10 cases (30%) showed a low polysomy, 15 (45%) a high polysomy and 2 (6%) NSCLC were amplified. No significant differences between NSCLC and CRC lung metastases were found in relation to disomic or polysomic status. In addition, no correlation between EGFR GCN and EGFR immunohistochemical overexpression was found. Furthermore, we compared CISH results with those obtained by FISH on the same samples and we found 97% overall agreement between the two assays (k = 0.78, p < 0.0001). Two cases were amplified with both assays, whereas 1 case of NSCLC was amplified by FISH only. CISH sensitivity was 67%, the specificity and positive predictive value (PPV) was 100%, and the negative predictive value (NPV) was 97%. Conclusions Our study shows that CISH is a valid method to detect EGFR GCN in cell blocks from FNAC of primary NSCLC or metastatic CRC to the lung. PMID:20843314

  10. Radix Tetrastigma hemsleyani flavone inhibits proliferation, migration, and invasion of human lung carcinoma A549 cells

    PubMed Central

    Zhong, Liangrui; Zheng, Junxian; Sun, Qianqian; Wei, Kemin; Hu, Yijuan

    2016-01-01

    Radix Tetrastigma hemsleyani flavone (RTHF) is widely used as a traditional herb and has detoxification and anti-inflammatory effects. In this study, we investigated the potential effects of RTHF on the growth and metastasis of human lung adenocarcinoma A549 cells and evaluated its mechanisms. A549 cells were treated with RTHF at various concentrations for different periods. In vitro Cell Counting Kit-8 assay and colony formation methods showed that RTHF had dose- and time-dependent antiproliferation effects on A549 cells. A cell adhesion assay showed that RTHF decreased A549 cell adhesion in a dose-dependent manner. Cell invasion and migration were investigated using the Transwell assay and observed using an inverted microscope; the results showed that cell metastasis was significantly lower in the treatment group than that in the control group (P<0.01). Expression of metastasis-related matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) was detected by real-time polymerase chain reaction and Western blotting. The results showed that the expression of MMP-2, MMP-9, and TIMP-1 decreased, while that of TIMP-2 increased significantly in the RTHF group when compared with the results of the control group. These results show that RTHF exhibits antigrowth and antimetastasis activity in lung cancer A549 cells by decreasing the expression of MMP-2/-9 and TIMP-1 and increasing that of TIMP-2. PMID:26893573

  11. Pituitary metastasis of lung neuroendocrine carcinoma: case report and literature review.

    PubMed

    Siqueira, Pedro Freire de; Mathez, Andréia Latanza Gomes; Pedretti, Denize Borges; Abucham, Julio

    2015-12-01

    Metastasis to the pituitary gland is an unusual situation in clinical practice, but the frequency thereof is increasing due to the increased survival of cancer patients, and greater availability of imaging. In most cases, they are found between the sixth and seventh decades of life, as determined in image examination of patients with known malignant neoplasm, but, generally, asymptomatic with respect to pituitary involvement. The most common primary sites are breast in women and lung in men. We present the case of a 64-year-old patient with clinical visual changes, polyuria, polydipsia, and decreased level of consciousness whose tests showed pan-hypopituitarism, hypernatremia and low urine specific gravity, and extensive mass in sellar region. Diabetes insipidus was confirmed and treated, corticotrophic and thyroid deficits were corrected and then the patient underwent resection by transsphenoidal surgery. The histopathological and immunohistochemistry analysis revealed pituitary metastasis of lung neuroendocrine tumor. Subsequently, a chest CT scan showed pulmonary mass consistent with primary neoplasm. Despite the water and electrolyte correction and intravenous glucocorticoid replacement, the patient continued to show decreased level of consciousness due to compression of the brain stem by the pituitary mass, evolving to death. The purpose is to call attention to the differential diagnosis of invasive lesions of the sellar region, mainly in individuals over 50 years and/or when associated with diabetes insipidus, as it may be a case of metastasis, although there is no known primary neoplasm. PMID:26677090

  12. Radiation Therapy and MK-3475 for Patients With Recurrent/Metastatic Head and Neck Cancer, Renal Cell Cancer, Melanoma, and Lung Cancer

    ClinicalTrials.gov

    2016-10-18

    Head and Neck Squamous Cell Carcinoma; Metastatic Renal Cell Cancer; Recurrent Head and Neck Carcinoma; Recurrent Lung Carcinoma; Recurrent Renal Cell Carcinoma; Recurrent Skin Carcinoma; Stage III Renal Cell Cancer; Stage IV Lung Cancer; Stage IV Skin Melanoma

  13. Methoxyamine, Pemetrexed Disodium, Cisplatin, and Radiation Therapy in Treating Patients With Stage IIIA-IV Non-small Cell Lung Cancer

    ClinicalTrials.gov

    2016-10-05

    Metastatic Malignant Neoplasm in the Brain; Stage IIIA Large Cell Lung Carcinoma; Stage IIIA Lung Adenocarcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Large Cell Lung Carcinoma; Stage IIIB Lung Adenocarcinoma; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Large Cell Lung Carcinoma; Stage IV Lung Adenocarcinoma; Stage IV Non-Small Cell Lung Cancer

  14. Cancer-testis antigen lymphocyte antigen 6 complex locus K is a serologic biomarker and a therapeutic target for lung and esophageal carcinomas.

    PubMed

    Ishikawa, Nobuhisa; Takano, Atsushi; Yasui, Wataru; Inai, Kouki; Nishimura, Hitoshi; Ito, Hiroyuki; Miyagi, Yohei; Nakayama, Haruhiko; Fujita, Masahiro; Hosokawa, Masao; Tsuchiya, Eiju; Kohno, Nobuoki; Nakamura, Yusuke; Daigo, Yataro

    2007-12-15

    Gene expression profile analyses of non-small cell lung carcinomas (NSCLC) and esophageal squamous cell carcinomas (ESCC) revealed that lymphocyte antigen 6 complex locus K (LY6K) was specifically expressed in testis and transactivated in a majority of NSCLCs and ESCCs. Immunohistochemical staining using 406 NSCLC and 265 ESCC specimens confirmed that LY6K overexpression was associated with poor prognosis for patients with NSCLC (P = 0.0003), as well as ESCC (P = 0.0278), and multivariate analysis confirmed its independent prognostic value for NSCLC (P = 0.0035). We established an ELISA to measure serum LY6K and found that the proportion of the serum LY6K-positive cases was 38 of 112 (33.9%) NSCLC and 26 of 81 (32.1%) ESCC, whereas only 3 of 74 (4.1%) healthy volunteers were falsely diagnosed. In most cases, there was no correlation between serum LY6K and conventional tumor markers of carcinoembryonic antigen (CEA) and cytokeratin 19-fragment (CYFRA 21-1) values. A combined ELISA for both LY6K and CEA classified 64.7% of lung adenocarcinoma patients as positive, and the use of both LY6K and CYFRA 21-1 increased sensitivity in the detection of lung squamous cell carcinomas and ESCCs up to 70.4% and 52.5%, respectively, whereas the false positive rate was 6.8% to 9.5%. In addition, knocked down of LY6K expression with small interfering RNAs resulted in growth suppression of the lung and esophageal cancer cells. Our data imply that a cancer-testis antigen, LY6K, should be useful as a new type of tumor biomarker and probably as a target for the development of new molecular therapies for cancer treatment.

  15. Mushroom β-Glucan May Immunomodulate the Tumor-Associated Macrophages in the Lewis Lung Carcinoma.

    PubMed

    Wang, Wan-Jhen; Wu, Yu-Sheng; Chen, Sherwin; Liu, Chi-Feng; Chen, Shiu-Nan

    2015-01-01

    The present study showed that oral mushroom beta-glucan treatment significantly increased IFN-γ mRNA expression but significantly reduced COX-2 mRNA expression within the lung. For LLC tumor model, oral Ganoderma lucidum or Antrodia camphorata polysaccharides treatments significantly reduced TGF-β production in serum. In addition, IL-12 and IFN-γ mRNA expression were significantly increased, but IL-6, IL-10, COX-2, and TGF-β mRNA expression were substantially following oral mushroom polysaccharides treatments. The study highlights the efficacious effect of mushroom polysaccharides for ameliorating the immune suppression in the tumor microenvironment. Increased M1 phenotype of tumor-associated macrophages and attenuated M2 phenotype of tumor-associated macrophages could be achieved by ingesting mushroom polysaccharides.

  16. Limbic encephalitis. A rare presentation of the small-cell lung carcinoma.

    PubMed

    den Hollander, A M; van Hulst, A M; Meerwaldt, J D; Haasjes, J G

    1989-11-01

    Two patients with an acute organic brain syndrome and accompanying neurological symptoms are described. Extensive work up showed that both patients suffered from small-cell lung cancer. Cerebral metastases were absent. Following chemotherapy and radiotherapy to the primary tumor one of the two patients showed a complete remission of psychiatric symptoms for one year. A paraneoplastic origin of this syndrome, in the literature known as limbic encephalitis, is postulated. The exact cause of this syndrome is yet unknown. Recent research reveals data indicating an immunological pathogenesis. The major clinical importance of this (neuro)-psychiatric syndrome is that its appearance may serve as a warning sign for an occult malignancy; furthermore, effective treatment of the primary malignancy can reverse the encephalitis. Thus antitumor therapy can result in a prolonged survival and considerably improved quality of life. PMID:2553530

  17. Tumor-suppressive microRNA-29 family inhibits cancer cell migration and invasion directly targeting LOXL2 in lung squamous cell carcinoma

    PubMed Central

    MIZUNO, KEIKO; SEKI, NAOHIKO; MATAKI, HIROKO; MATSUSHITA, RYOSUKE; KAMIKAWAJI, KAZUTO; KUMAMOTO, TOMOHIRO; TAKAGI, KOICHI; GOTO, YUSUKE; NISHIKAWA, RIKA; KATO, MAYUKO; ENOKIDA, HIDEKI; NAKAGAWA, MASAYUKI; INOUE, HIROMASA

    2016-01-01

    Lung cancer remains the most frequent cause of cancer-related death in developed countries. A recent molecular-targeted strategy has contributed to improvement of the remarkable effect of adenocarcinoma of the lung. However, such treatment has not been developed for squamous cell carcinoma (SCC) of the disease. Our recent studies of microRNA (miRNA) expression signatures of human cancers showed that the microRNA-29 family (miR-29a, miR-29b and miR-29c) significantly reduced cancer tissues compared to normal tissues. These findings suggest that miR-29s act as tumor-suppressors by targeting several oncogenic genes. The aim of the study was to investigate the functional significance of miR-29s in lung SCC and to identify miR-29s modulating molecular targets in lung SCC cells. Restoration of all mature members of the miR-29s inhibited cancer cell migration and invasion. Gene expression data combined in silico analysis and luciferase reporter assays demonstrated that the lysyl oxidase-like 2 (LOXL2) gene was a direct regulator of tumor-suppressive miR-29s. Moreover, overexpressed LOXL2 was confirmed in lung SCC clinical specimens, and silencing of LOXL2 inhibited cancer cell migration and invasion in lung SCC cell lines. Our present data suggested that loss of tumor-suppressive miR-29s enhanced cancer cell invasion in lung SCC through direct regulation of oncogenic LOXL2. Elucidation of the novel lung SCC molecular pathways and targets regulated by tumor-suppressive miR-29s will provide new insights into the potential mechanisms of oncogenesis and metastasis of the disease. PMID:26676674

  18. Tumor-suppressive microRNA-29 family inhibits cancer cell migration and invasion directly targeting LOXL2 in lung squamous cell carcinoma.

    PubMed

    Mizuno, Keiko; Seki, Naohiko; Mataki, Hiroko; Matsushita, Ryosuke; Kamikawaji, Kazuto; Kumamoto, Tomohiro; Takagi, Koichi; Goto, Yusuke; Nishikawa, Rika; Kato, Mayuko; Enokida, Hideki; Nakagawa, Masayuki; Inoue, Hiromasa

    2016-02-01

    Lung cancer remains the most frequent cause of cancer-related death in developed countries. A recent molecular-targeted strategy has contributed to improvement of the remarkable effect of adenocarcinoma of the lung. However, such treatment has not been developed for squamous cell carcinoma (SCC) of the disease. Our recent studies of microRNA (miRNA) expression signatures of human cancers showed that the microRNA-29 family (miR‑29a, miR‑29b and miR‑29c) significantly reduced cancer tissues compared to normal tissues. These findings suggest that miR‑29s act as tumor-suppressors by targeting several oncogenic genes. The aim of the study was to investigate the functional significance of miR‑29s in lung SCC and to identify miR‑29s modulating molecular targets in lung SCC cells. Restoration of all mature members of the miR‑29s inhibited cancer cell migration and invasion. Gene expression data combined in silico analysis and luciferase reporter assays demonstrated that the lysyl oxidase-like 2 (LOXL2) gene was a direct regulator of tumor‑suppressive miR‑29s. Moreover, overexpressed LOXL2 was confirmed in lung SCC clinical specimens, and silencing of LOXL2 inhibited cancer cell migration and invasion in lung SCC cell lines. Our present data suggested that loss of tumor-suppressive miR‑29s enhanced cancer cell invasion in lung SCC through direct regulation of oncogenic LOXL2. Elucidation of the novel lung SCC molecular pathways and targets regulated by tumor-suppressive miR‑29s will provide new insights into the potential mechanisms of oncogenesis and metastasis of the disease.

  19. Primary renal carcinoid tumour with lung metastasis misdiagnosed as renal cell carcinoma.

    PubMed

    Daboul, Nour; Monga, Dulabh; Bunker, Mark

    2016-01-01

    A 58-year-old man with a history of metastatic renal cell carcinoma (RCC) diagnosed 10 years prior, status post right nephrectomy, presented for evaluation of pulmonary nodules. A year after the nephrectomy, he had undergone cutaneous metastasectomy in the right flank area, and a further 2 years later he had had his second cutaneous metastasectomy in the right chest wall. Both cutaneous pathologies had, at the time, shown metastatic neoplasm with histological features compatible with those of the previous renal tumour. He was treated with sorafenib. 3 years later he developed asymptomatic pulmonary nodules, which gradually doubled in size over the next 2.5 years. He underwent bronchoscopy and left lower lobe biopsy. Pathology revealed a metastatic renal carcinoid/neuroendocrine tumour. Second review of the previous renal neoplasm and the cutaneous metastatic pathology showed trabecular architecture, consistent with carcinoid, but mimicking the long parallel arrays that have been described in some cases of papillary RCC. PMID:26951438

  20. p53 gene product expression in resected non-small cell carcinoma of the lung, with studies of concurrent cytological preparations and microwave antigen retrieval.

    PubMed Central

    Binks, S; Clelland, C A; Ronan, J; Bell, J

    1997-01-01

    AIM: To document the frequency and extent of p53 gene product expression in paraffin sections of resected non-small cell carcinoma of the lung and in cytological preparations of the same tumours; to determine the effect of microwave antigen retrieval on antigen detection. METHODS: Representative paraffin sections of 50 non-small cell carcinomas were stained with an antibody to p53 gene product (DO-7) both with and without prior microwave antigen retrieval. Cytoblocks and cell smears obtained from 19 cases were similarly stained. RESULTS: Using a histochemical scoring system (0-300) which takes into account staining intensity and extent, 78% (n = 39) of microwave pretreated paraffin sections and 52% (n = 26) of non-pretreated sections scored between 5 and 300; p = 0.001; 56% (n = 28) of microwave pretreated sections and only 2% (n = 1) of non-pretreated sections scored between 100 and 300 (p = 0.0001); 75% of direct smears of tumours and 80% of cytoblocks stained similarly to the paraffin sections of the resected specimens. No smears or cytoblocks stained positively when the sections of the resected specimen were negative. CONCLUSIONS: As up to 78% of non-small cell lung carcinomas overexpress p53 gene product, this may prove to be a valuable diagnostic method in biopsy or cytological material when the morphological diagnosis is uncertain. Microwave antigen retrieval is effective on formalin fixed tissue. Images PMID:9215149

  1. EF5 in Measuring Tumor Hypoxia in Patients With Stage I-III Non-Small Cell Lung Cancer

    ClinicalTrials.gov

    2015-04-10

    Stage IA Non-Small Cell Lung Carcinoma; Stage IB Non-Small Cell Lung Carcinoma; Stage IIA Non-Small Cell Lung Carcinoma; Stage IIB Non-Small Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer

  2. Videothoracoscopic resection for lung cancer: moving towards a "standard of care".

    PubMed

    Treasure, Tom

    2016-08-01

    Videothoracic surgery for lung cancer is now an established practice but there is a division of opinion between surgeons whose aim is to spare all patients a thoracotomy and those who have not adopted videoscopic methods for routine lobectomy. The latter remain in the majority; most patients at present have a thoracotomy. Surgeons from Europe and America met in Catania, Sicily at the 3(rd) Mediterranean Symposium on Thoracic Surgical Oncology to explore the evidence and the routes to making videothoracoscopic surgery a standard of care. Evidence from one completed randomized controlled trial (RCT) and several propensity score matching studies indicate that less invasive surgery is at least as safe as thoracotomy. By the accepted standards of an oncological lobectomy which include clearance of the primary cancer and the intended lymphadenectomy or sampling, the operations are equivalent. Clinical effectiveness in achieving long-term cancer free survival is likely. However, the co-existance of videothoracoscopy has encouraged smaller non-muscle cutting incisions and the avoidance of rib spreading, narrowing whatever gap there may have been in terms of the patients' experience. PMID:27621911

  3. Videothoracoscopic resection for lung cancer: moving towards a “standard of care”

    PubMed Central

    2016-01-01

    Videothoracic surgery for lung cancer is now an established practice but there is a division of opinion between surgeons whose aim is to spare all patients a thoracotomy and those who have not adopted videoscopic methods for routine lobectomy. The latter remain in the majority; most patients at present have a thoracotomy. Surgeons from Europe and America met in Catania, Sicily at the 3rd Mediterranean Symposium on Thoracic Surgical Oncology to explore the evidence and the routes to making videothoracoscopic surgery a standard of care. Evidence from one completed randomized controlled trial (RCT) and several propensity score matching studies indicate that less invasive surgery is at least as safe as thoracotomy. By the accepted standards of an oncological lobectomy which include clearance of the primary cancer and the intended lymphadenectomy or sampling, the operations are equivalent. Clinical effectiveness in achieving long-term cancer free survival is likely. However, the co-existance of videothoracoscopy has encouraged smaller non-muscle cutting incisions and the avoidance of rib spreading, narrowing whatever gap there may have been in terms of the patients’ experience. PMID:27621911

  4. Videothoracoscopic resection for lung cancer: moving towards a “standard of care”

    PubMed Central

    2016-01-01

    Videothoracic surgery for lung cancer is now an established practice but there is a division of opinion between surgeons whose aim is to spare all patients a thoracotomy and those who have not adopted videoscopic methods for routine lobectomy. The latter remain in the majority; most patients at present have a thoracotomy. Surgeons from Europe and America met in Catania, Sicily at the 3rd Mediterranean Symposium on Thoracic Surgical Oncology to explore the evidence and the routes to making videothoracoscopic surgery a standard of care. Evidence from one completed randomized controlled trial (RCT) and several propensity score matching studies indicate that less invasive surgery is at least as safe as thoracotomy. By the accepted standards of an oncological lobectomy which include clearance of the primary cancer and the intended lymphadenectomy or sampling, the operations are equivalent. Clinical effectiveness in achieving long-term cancer free survival is likely. However, the co-existance of videothoracoscopy has encouraged smaller non-muscle cutting incisions and the avoidance of rib spreading, narrowing whatever gap there may have been in terms of the patients’ experience.

  5. Antrodia cinnamomea alleviates cisplatin-induced hepatotoxicity and enhances chemo-sensitivity of line-1 lung carcinoma xenografted in BALB/cByJ mice.

    PubMed

    Huang, Tse-Hung; Chiu, Yi-Han; Chan, Yi-Lin; Wang, Hang; Li, Tsung-Lin; Liu, Chien-Yin; Yang, Cheng-Ta; Lee, Tzung-Yan; You, Jyh-Sheng; Hsu, Kuang-Hung; Wu, Chang-Jer

    2015-09-22

    Whereas cisplatin (cis-diamminedichloroplatinum II) is a first-line medicine to treat solid cancerous tumors, it often causes serious side effects. New medicines that have an equivalent or even better therapeutic effect but with free or less side effects than cisplatin are highly anticipated in cancer therapy. Recent reports revealed that Antrodia cinnamomea (AC) possesses hepatoprotective activity in addition to anticancer. In this study, we wanted to know whether AC enhances chemo-sensitivity of cisplatin and/or alleviates cisplatin-induced hepatotoxicity, as well as the underlying mechanisms thereof. Our results indicated that AC inhibited proliferation of line-1 lung carcinoma cells and rescued hepatic HepG2 cells from cisplatin-induced cell death in vitro. The fact is that AC and cisplatin synergized to constrain growth of line-1 lung carcinoma cells in BALB/cByJ mice. Quantitative real-time PCR further revealed that AC promoted expression of apoptosis-related genes, while it decreased expression of NF-κB and VEGF in tumor tissues. In liver, AC reduced cisplatin-induced liver dysfunctions, liver inflammation and hepatic apoptosis in addition to body weight restoration. In summary, AC is able to increase cisplatin efficacy by triggering expression of apoptosis-related genes in line-1 lung cancer cells as well as to protect liver from tissue damage by avoiding cisplatin-induced hepatic inflammation and cell death. PMID:26325335

  6. Costunolide induces G1/S phase arrest and activates mitochondrial-mediated apoptotic pathways in SK-MES 1 human lung squamous carcinoma cells

    PubMed Central

    HUA, PEIYAN; ZHANG, GUANGXIN; ZHANG, YIFAN; SUN, MEI; CUI, RANJI; LI, XIN; LI, BINGJIN; ZHANG, XINGYI

    2016-01-01

    Despite the availability of several therapeutic options, a safer and more effective modality strategy is required for the treatment of lung cancer. Costunolide, a sesquiterpene lactone which isolated from the Saussurea lappa, has potent anticancer properties. In the present study, the effects of costunolide on cell viability, the cell cycle and apoptosis in SK-MES-1 human lung squamous carcinoma cells were investigated. Costunolide induced morphological changes and inhibited growth of SK-MES-1 cells growth. Flow cytometric analysis data demonstrated that costunolide significantly induced apoptosis of SK-MES-1 cells and induced cell cycle arrest at G1/S phase in a dose-dependent manner. Through upregulation in the expression of p53 and Bax, and downregulation in the expression of Bcl-2 and activation of caspase-3, costunolide-induced apoptosis was confirmed by western blot analysis. In addition, the significant loss of mitochondrial membrane potential indicated that costunolide may induce apoptosis via the mitochondria-dependent pathway in SK-MES-1 cells. These results highlight the potential effects of costunolide as an anti-cancer agent in a human lung squamous carcinoma cell line. PMID:27073552

  7. Clinical and metabolic parameters in non-small cell lung carcinoma and colorectal cancer patients with and without KRAS mutations.

    PubMed

    Yilmaz, Ahmet; Mohamed, Nehad; Patterson, Kara A; Tang, Yan; Shilo, Konstantin; Villalona-Calero, Miguel A; Davis, Michael E; Zhou, Xiao-Ping; Frankel, Wendy; Otterson, Gregory A; Zhao, Weiqiang

    2014-09-01

    Lung cancer (LC) and colorectal cancer (CRC) are the first and second deadliest types of cancer worldwide. EGFR-based therapy has been used in the treatment of these cancers with variable success. Presence of mutations in the KRAS driver oncogene, possibly induced by environmental factors such as carcinogens in diet and cigarette smoke, may confer worse prognosis and resistance to treatment for reasons not fully understood. Data on possible associations between KRAS mutational status and clinical and metabolic parameters, which may help in clinical management, as well as in identifying risk factors for developing these cancers, are limited in the current literature. We sequenced the KRAS gene and investigated the associations of variations in 108 patients with non-small cell lung carcinoma (NSCLC), the most common form of LC, and in 116 patients with CRC. All of the mutations originated from the guanosine nucleotide and over half of all transversions in NSCLC and CRC were c.34 G>T and c.35 G>T, respectively. c.35 G>A was the most frequent type of transition in both cancers. Excluding smoking, the clinical and metabolic parameters in patients carrying mutant and wild type KRAS were similar except that the CRC patients with transversion mutations were 8.6 years younger than those carrying the transitions (P < 0.01). Dyslipidemia, hypertension, family cancer history, and age of diagnosis older than 60 years were more frequent in NSCLC than CRC (P ≤ 0.04). These results suggest that most of the clinical and metabolic parameters investigated in this study are probably not associated with the more aggressive phenotype and differences in response to EGFR-based treatment previously reported in patients with KRAS mutations. However, the increased rates of abnormal metabolic parameters in patients with NSCLC in comparison to CRC indicate that these parameters may be more important in the management of NSCLC. CRC patients carrying transition mutations are older than those

  8. Chromosomal alterations in the clonal evolution to the metastatic stage of squamous cell carcinomas of the lung.

    PubMed

    Petersen, S; Aninat-Meyer, M; Schlüns, K; Gellert, K; Dietel, M; Petersen, I

    2000-01-01

    Comparative genomic hybridization (CGH) was applied to squamous cell carcinomas (SCC) of the lung to define chromosomal imbalances that are associated with the metastatic phenotype. In total, 64 lung SCC from 50 patients were investigated, 25 each with or without evidence of metastasis formation. The chromosomal imbalances summarized by a CGH histogram of the 50 cases revealed deletions most frequently on chromosomes 1p21-p31, 2q34-q36, 3p, 4p, 4q, 5q, 6q14-q24, 8p, 9p, 10q, 11p12-p14, 13q13-qter, 18q12-qter and 21q21. DNA over-representations were most pronounced for chromosomes 1q11-q25, 1q32-q41, 3q, 5p, 8q22-qter, 11q13, 12p, 17q21-q22, 17q24-q25, 19, 20q and 22q. In ten cases, paired samples of primaries and at least one metastasis were analysed. The comparison revealed a considerable chromosomal instability and genetic heterogeneity; however, the CGH pattern indicated a clonal relationship in each case. The difference in histograms from the metastatic and non-metastatic tumour groups was most useful in pinpointing chromosomal imbalances associated with the metastatic phenotype, indicating that the deletions at 3p12-p14, 3p21, 4p15-p16, 6q24-qter, 8p22-p23, 10q21-qter and 21q22, as well as the over-representations at 1q21-q25, 8q, 9q34, 14q12 and 15q12-q15, occurred significantly more often in the metastatic tumour group. The comparison of the paired samples confirmed these findings in individual cases and suggested distinct genetic changes, in particular the extension of small interstitial deletions, during tumour progression. Importantly, metastasis-associated lesions were frequently detectable in the primary tumour providing a method of identifying patients at risk for tumour dissemination. Individual profiles and histograms are accessible at our web site http://amba.charite.de/cgh.

  9. [RAdio-chemo-surgical combined treatment of non-small cell lung carcinoma N2].

    PubMed

    Rovea, P; Sola, B; Boidi Trotti, A; Gabriele, A M; Fracchia, F; Casadio, C; Bretti, S

    1993-06-01

    As yet, no optimal treatment for stage-IIIA non-small-cell lung cancer (NSCLC) has been established. Particularly, in the patients with stage-IIIA N2 disease, surgical resection for cure is limited to few selected patients. Of late, a number of studies have suggested that such treatment modalities as chemotherapy, radiotherapy and surgery might be combined to improve treatment efficacy. Based on these conclusions, a cooperative study for N2 NSCLC patients was performed. Treatment included continuous CDDP infusion (6 mg/m2/day) and concomitant irradiation. Fifteen patients were examined. After neoadjuvant treatment, 4 patients were found to have unresectable lesions for local disease progression or metastasis. Eleven patients underwent complete resection (73% resectability). Follow-up ranged 6 to 32 months: 6 patients are now free from relapse (respectively at 31, 28, 23, 14, 12 and 3 months) and 1 is alive with adrenal gland metastasis. Overall and disease-free survival rates are 40.6% and 31.5%, respectively. Our preliminary results indicated that this protocol is well tolerated. Resectability was good and tumor sterilization rate was satisfying (complete T and N sterilization in 6 cases, sterilization of either T or N in 3 cases). The patients with non-adenocarcinoma histology exhibited better local control and prognosis than those with histologic diagnosis of adenocarcinoma.

  10. [RAdio-chemo-surgical combined treatment of non-small cell lung carcinoma N2].

    PubMed

    Rovea, P; Sola, B; Boidi Trotti, A; Gabriele, A M; Fracchia, F; Casadio, C; Bretti, S

    1993-06-01

    As yet, no optimal treatment for stage-IIIA non-small-cell lung cancer (NSCLC) has been established. Particularly, in the patients with stage-IIIA N2 disease, surgical resection for cure is limited to few selected patients. Of late, a number of studies have suggested that such treatment modalities as chemotherapy, radiotherapy and surgery might be combined to improve treatment efficacy. Based on these conclusions, a cooperative study for N2 NSCLC patients was performed. Treatment included continuous CDDP infusion (6 mg/m2/day) and concomitant irradiation. Fifteen patients were examined. After neoadjuvant treatment, 4 patients were found to have unresectable lesions for local disease progression or metastasis. Eleven patients underwent complete resection (73% resectability). Follow-up ranged 6 to 32 months: 6 patients are now free from relapse (respectively at 31, 28, 23, 14, 12 and 3 months) and 1 is alive with adrenal gland metastasis. Overall and disease-free survival rates are 40.6% and 31.5%, respectively. Our preliminary results indicated that this protocol is well tolerated. Resectability was good and tumor sterilization rate was satisfying (complete T and N sterilization in 6 cases, sterilization of either T or N in 3 cases). The patients with non-adenocarcinoma histology exhibited better local control and prognosis than those with histologic diagnosis of adenocarcinoma. PMID:8393206

  11. Steroid sulphatase and oestrogen sulphotransferase in human non-small-cell lung carcinoma

    PubMed Central

    Iida, S; Kakinuma, H; Miki, Y; Abe, K; Sakurai, M; Suzuki, S; Niikawa, H; Akahira, J; Suzuki, T; Sasano, H

    2013-01-01

    Background: Steroid sulphatase (STS) is one of the steroid-metabolising enzymes involved in desulphating inactive steroid sulphates and oestrogen sulphotransferase (EST) sulphates active oestrogen. The roles of both STS and EST have not been examined in oestrogen-dependent non-small-cell lung cancer (NSCLC). Methods: We evaluated the immunoreactivity of STS and EST in NSCLC cases using immunohistochemistry. The function of STS and EST was further demonstrated using NSCLC cell lines. Results: The immunoreactivity of STS and EST was detected in 49.5% and 27.8% of NSCLC cases, respectively. The immunoreactivity of STS was significantly higher in female adenocarcinoma cases. The STS-positive NSCLCs were also significantly correlated in an inversed manner with tumour size and cell proliferation and tended to be associated with better clinical outcome. However, the immunoreactivity of EST was significantly correlated with intracellular oestradiol concentration. Results of in vitro analysis demonstrated that oestrone sulphate (E1-S) induced and pregnenolone sulphate (Preg-S) inhibited the proliferation in STS-expressing cell lines. The inhibition by Preg-S was reversed by a specific progesterone receptor blocker. Simultaneous addition of E1-S and Preg-S significantly suppressed the proliferation. Conclusion: In NSCLC patients, STS is considered a good prognostic factor. Results of our present study also indicated the benefits of potential progesterone therapy for NSCLC patients. PMID:23531699

  12. Crosstalk between Integrin αvβ3 and Estrogen Receptor-α Is Involved in Thyroid Hormone-Induced Proliferation in Human Lung Carcinoma Cells

    PubMed Central

    Meng, Ran; Tang, Heng-Yuan; Westfall, Jennifer; London, David; Cao, James H.; Mousa, Shaker A.; Luidens, Mary; Hercbergs, Aleck; Davis, Faith B.; Davis, Paul J.; Lin, Hung-Yun

    2011-01-01

    A cell surface receptor for thyroid hormone that activates extracellular regulated kinase (ERK) 1/2 has been identified on integrin αvβ3. We have examined the actions of thyroid hormone initiated at the integrin on human NCI-H522 non-small cell lung carcinoma and NCI-H510A small cell lung cancer cells. At a physiologic total hormone concentration (10−7 M), T4 significantly increased proliferating cell nuclear antigen (PCNA) abundance in these cell lines, as did 3, 5, 3′-triiodo-L-thyronine (T3) at a supraphysiologic concentration. Neutralizing antibody to integrin αvβ3 and an integrin-binding Arg-Gly-Asp (RGD) peptide blocked thyroid hormone-induced PCNA expression. Tetraiodothyroacetic acid (tetrac) lacks thyroid hormone function but inhibits binding of T4 and T3 to the integrin receptor; tetrac eliminated thyroid hormone-induced lung cancer cell proliferation and ERK1/2 activation. In these estrogen receptor-α (ERα)-positive lung cancer cells, thyroid hormone (T4>T3) caused phosphorylation of ERα; the specific ERα antagonist ICI 182,780 blocked T4-induced, but not T3-induced ERK1/2 activation, as well as ERα phosphorylation, proliferating-cell nuclear antigen (PCNA) expression and hormone-dependent thymidine uptake by tumor cells. Thus, in ERα-positive human lung cancer cells, the proliferative action of thyroid hormone initiated at the plasma membrane is at least in part mediated by ERα. In summary, thyroid hormone may be one of several endogenous factors capable of supporting proliferation of lung cancer cells. Activity as an inhibitor of lung cancer cell proliferation induced at the integrin receptor makes tetrac a novel anti-proliferative agent. PMID:22132110

  13. Differential expression of STAT5 and Bcl-xL, and high expression of Neu and STAT3 in non-small-cell lung carcinoma.

    PubMed

    Sánchez-Ceja, S G; Reyes-Maldonado, E; Vázquez-Manríquez, M E; López-Luna, J J; Belmont, A; Gutiérrez-Castellanos, S

    2006-11-01

    Experimental evidence suggests that in lung cancer, development, progression and an increased proliferation rate can be linked to apoptosis-related factors. The objective of this study is to evaluate the status of Neu, signal transducer and activator of transcription (STAT)-3, STAT5 and Bcl-xL expression in non-small-cell lung cancer. We investigated the immunohistochemical expression of these proteins in 92 non-small-cell lung cancer specimens to establish their role in lung cancer pathogenesis. Neu was overexpressed in 65% of cases, and although STAT3 was overexpressed in 52.1% in cytoplasm, it was expressed in nucleus (activated) in 60.8%. Meanwhile, STAT5 was found overexpressed in 41.3% in cytoplasm and 32.6% in nucleus. Thus, Bcl-xL was overexpressed in cytoplasm in 81.5%. Interestingly, we found nuclear expression of Bcl-xL in 30.4% of cases. Finally, we found correlation among histological types of lung cancer and nuclear expression of both STAT5 (P=0.005) and nuclear Bcl-xL (P=0.003). Besides, nuclear expression of Bcl-xL was correlated with TNM stage IV (distant metastasis) (P=0.02). These results suggest for the first time, a relevant role for STAT5 and Bcl-xL as apoptosis-regulatory proteins in the pathogenesis of lung cancer, and overexpression of both Neu and activated STAT3, could be related with the proliferation rate in lung carcinoma cells.

  14. [Anti-tumor effect of the whole worm extract of Ascaris lumbricoides on Lewis lung carcinoma in mice].

    PubMed

    Yang, Xiao-Jun; Yang, Jun-Ping; Huang, Yan-Qin; Liang, Hua; Yuan, Keng

    2013-12-01

    Forty-five C57BL/6 mice were randomly divided into five groups (A-E). Group B and D served as the control group of A and C. Each mouse of group A was intraperitoneally injected with 0.1 ml whole worm extract of Ascaris lumbricoides every other day, and 10 days later injected with 0.1 ml Lewis lung carcinoma (LLC) cells at right axillary subcutaneously region. Mice of group B were injected with normal saline and then developed tumor model. Each mouse of group C was injected with 0.1 ml LLC cells, and two days later, injected with 0.1 ml whole worm extract of A. lumbricoides every other day for 5 times. After the tumor model developed, mice in group D were injected with normal saline. Group E was the negative control group. Time intervals between implantation and active growth and tumor weight were recorded. Tumor inhibition rate was calculated. The average time interval between tumor implantation and measurable tumor growth for groups A, B, C and D was (7.0 +/-1.1), (6.0 +/- 0.7), (9.0 +/- 1.2) and (7.0 +/- 0.9) days. Tumor weight of [(338.9 +/- 282.2) mg] (P < 0.05). The tumor inhibition rate group A [(722.2 +/- 413.5) mg] was heavier than that of group B was the highest in group C (33.3%). Tumor weight of group C [(237.8 +/- 101.8) mg] was lighter than that of group D [(356.7 +/- 176.9) mg] (P < 0.05). The results indicated that the tumor formation is affected by the whole worm extract of A. lumbricoides which may have an inhibitory effect on tumour growth.

  15. Profiling Analysis of Histone Modifications and Gene Expression in Lewis Lung Carcinoma Murine Cells Resistant to Anti-VEGF Treatment

    PubMed Central

    Du, Yanhua; Chen, Kaiming; Liu, Zhenping; Li, Bing; Li, Jie; Tao, Fei; Gu, Hua; Jiang, Cizhong; Fang, Jianmin

    2016-01-01

    Tumor cells become resistant after long-term use of anti-VEGF (vascular endothelial growth factor) agents. Our previous study shows that treatment with a VEGF inhibitor (VEGF-Trap) facilitates to develop tumor resistance through regulating angiogenesis-related genes. However, the underlying molecular mechanisms remain elusive. Histone modifications as a key epigenetic factor play a critical role in regulation of gene expression. Here, we explore the potential epigenetic gene regulatory functions of key histone modifications during tumor resistance in a mouse Lewis lung carcinoma (LLC) cell line. We generated high resolution genome-wide maps of key histone modifications in sensitive tumor sample (LLC-NR) and resistant tumor sample (LLC-R) after VEGF-Trap treatment. Profiling analysis of histone modifications shows that histone modification levels are effectively predictive for gene expression. Composition of promoters classified by histone modification state is different between LLC-NR and LLC-R cell lines regardless of CpG content. Histone modification state change between LLC-NR and LLC-R cell lines shows different patterns in CpG-rich and CpG-poor promoters. As a consequence, genes with different level of CpG content whose gene expression level are altered are enriched in distinct functions. Notably, histone modification state change in promoters of angiogenesis-related genes consists with their expression alteration. Taken together, our findings suggest that treatment with anti-VEGF therapy results in extensive histone modification state change in promoters with multiple functions, particularly, biological processes related to angiogenesis, likely contributing to tumor resistance development. PMID:27362259

  16. High-Dose Conformal Radiotherapy for Patients With Stage III Non-Small-Cell Lung Carcinoma

    SciTech Connect

    Nakayama, Hidetsugu; Satoh, Hiroaki; Kurishima, Koichi; Ishikawa, Hiroichi; Tokuuye, Koichi

    2010-11-01

    Purpose: To determine the effectiveness of high-dose conformal radiotherapy to the involved field for patients with Stage III non-small-cell lung cancer (NSCLC). Methods and Materials: Between May 1999 and April 2006, a total of 100 consecutive patients with inoperable Stage IIIA or IIIB NSCLC with a performance score of 0 to 2 and treatment by radical radiotherapy combined with chemotherapy were included. Up to August 2002, 33 patients underwent conventional radiotherapy of 56 Gy to 66 Gy using anteroposterior opposite ports to the primary tumor and elective lymph nodes (conventional group). After September 2002, the remaining 67 patients underwent high-dose radiotherapy of 66 Gy to 84 Gy to the involved volume with three-dimensional (3-D) conformal radiotherapy (conformal group). Results: The median survival was 13.2 months (95% confidence interval [CI], 7.5-18.5 months) in the conventional group and 17.3 months (95% CI, 10.7- 24.0 months) in the conformal group. The overall survival at 3 years were 9.1% (95% CI, -0.7-18.9%) in the conventional group and 31.0% (95% CI, 18.9-43.1%) in the conformal group; the conformal group had a significantly better overall survival (p < 0.05). The radiotherapy method (hazard ratio = 0.55, p < 0.05) and performance status (hazard ratio = 1.48, p < 0.05) were shown to be statistically significant independent prognostic factors. Conclusions: Based on the practical experience reported here, 3-D conformal radiotherapy allowed dose escalation without excessive toxicity, and may improve overall survival rates for patients with Stage III NSCLC.

  17. Atorvastatin overcomes gefitinib resistance in KRAS mutant human non-small cell lung carcinoma cells.

    PubMed

    Chen, J; Bi, H; Hou, J; Zhang, X; Zhang, C; Yue, L; Wen, X; Liu, D; Shi, H; Yuan, J; Liu, J; Liu, B

    2013-09-26

    The exact influence of statins on gefitinib resistance in human non-small cell lung cancer (NSCLC) cells with KRAS mutation alone or KRAS/PIK3CA and KRAS/PTEN comutations remains unclear. This work found that transfection of mutant KRAS plasmids significantly suppressed the gefitinib cytotoxicity in Calu3 cells (wild-type KRAS). Gefitinib disrupted the Kras/PI3K and Kras/Raf complexes in Calu3 cells, whereas not in Calu3 KRAS mutant cells. These trends were corresponding to the expression of pAKT and pERK in gefitinib treatment. Atorvastatin (1 μM) plus gefitinib treatment inhibited proliferation, promoted cell apoptosis, and reduced the AKT activity in KRAS mutant NSCLC cells compared with gefitinib alone. Atorvastatin (5 μM) further enhanced the gefitinib cytotoxicity through concomitant inhibition of AKT and ERK activity. Atorvastatin could interrupt Kras/PI3K and Kras/Raf complexes, leading to suppression of AKT and ERK activity. Similar results were also obtained in comutant KRAS/PTEN or KRAS/PIK3CA NSCLC cells. Furthermore, mevalonate administration reversed the effects of atorvastatin on the Kras/Raf and Kras/PI3K complexes, as well as AKT and ERK activity in both A549 and Calu1 cells. The in vivo results were similar to those obtained in vitro. Therefore, mutant KRAS-mediated gefitinib insensitivity is mainly derived from failure to disrupt the Kras/Raf and Kras/PI3K complexes in KRAS mutant NSCLC cells. Atorvastatin overcomes gefitinib resistance in KRAS mutant NSCLC cells irrespective of PIK3CA and PTEN statuses through inhibition of HMG-CoA reductase-dependent disruption of the Kras/Raf and Kras/PI3K complexes.

  18. Prediction of Pathologic Grade and Prognosis in Mucoepidermoid Carcinoma of the Lung Using 18F-FDG PET/CT

    PubMed Central

    Park, Byungjoon; Kim, Hong Kwan; Choi, Yong Soo; Kim, Jhingook; Zo, Jae Il; Choi, Joon Young

    2015-01-01

    Objective The maximum standardized uptake value (SUVmax) of pulmonary mucoepidermoid carcinoma (PMEC) in fluorine-18fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) was evaluated as a preoperative predictor of pathologic grade and survival rate. Materials and Methods Twenty-three patients who underwent preoperative PET/CT and complete resection for PMEC were enrolled. The optimal cut-off SUVmax for tumor grade was calculated as 6.5 by receiver operating characteristic curve. The patients were divided into a high SUV group (n = 7) and a low SUV group (n = 16). Clinicopathologic features were compared between the groups by χ2 test and overall survival was determined by Kaplan-Meier analysis. Results The mean SUVmax was 15.4 ± 11.5 in the high SUV group and 3.9 ± 1.3 in the low SUV group. All patients except one from the low SUV group had low grade tumors and all had no nodal metastasis. The sensitivity and specificity of SUVmax from PET/CT for predicting tumor grade was 85.7% and 93.8%, respectively. During the follow-up period (mean, 48.6 ± 38.7 months), four patients from the high SUV group experienced cancer recurrence, and one died of cancer. In contrast, none of the low SUV group had recurrence or mortality. Five-year overall survival rate was significantly higher in the low SUV group (100% vs. 71.4%, p = 0.031). Conclusion Pulmonary mucoepidermoid carcinoma patients with high SUVmax in PET/CT had higher tumor grade, more frequent lymph node metastasis and worse long-term outcome. Therefore, PMEC patients with high uptake on PET/CT imaging might require aggressive mediastinal lymph node dissection and adjuvant therapies. PMID:26175595

  19. Crotoxin induces apoptosis and autophagy in human lung carcinoma cells in vitro via activation of the p38MAPK signaling pathway

    PubMed Central

    Han, Rong; Liang, Hui; Qin, Zheng-hong; Liu, Chun-yu

    2014-01-01

    Aim: Crotoxin (CrTX) is the primary toxin in South American rattlesnake (Crotalus durissus terrificus) venom, and exhibits antitumor and other pharmacological actions in vivo and in vitro. Here, we investigated the molecular mechanisms of the antitumor action of CrTX in human lung carcinoma cells in vitro. Methods: Human lung squamous carcinoma SK-MES-1 cells were tested. The cytotoxicity of CrTX was evaluated in both MTT and colony formation assays. Cell cycle was investigated with flow cytometry. Cell apoptosis was studied with Hoechst 33258 and Annexin V-FITC staining. The levels of relevant proteins were analyzed using Western blot assays. Results: CrTX (25, 50, 100 μmol/L) inhibited the growth and colony formation of SK-MES-1 cells in dose- and time-dependent manners. CrTX increased the proportion of S phase cells and dose-dependently induced cell apoptosis, accompanied by down-regulating the expression of proliferating cell nuclear antigen (PCNA), and increasing the level of cleaved caspase-3. Furthermore, CrTX dose-dependently increased the expression of autophagy-related proteins LC3-II and beclin 1, and decreased the level of p62 in the cells. Moreover, CrTX (50 μmol/L) significantly increased p38MAPK phosphorylation in the cells. Pretreatment of the cells with SB203580, a specific inhibitor of p38MAPK, blocked the inhibition of CrTX on cell proliferation, as well as CrTX-induced apoptosis and cleaved caspase-3 expression. Conclusion: The p38MAPK signaling pathway mediates CrTX-induced apoptosis and autophagy of human lung carcinoma SK-MES-1 cells in vitro. PMID:25132339

  20. Differential expression of Yes-associated protein is correlated with expression of cell cycle markers and pathologic TNM staging in non-small-cell lung carcinoma.

    PubMed

    Kim, Jin Man; Kang, Dong Wook; Long, Liang Zhe; Huang, Song-Mei; Yeo, Min-Kyung; Yi, Eunhee S; Kim, Kyung-Hee

    2011-03-01

    Yes-associated protein, a downstream effector of the Hippo signaling pathway, has been linked to progression of non-small-cell lung carcinoma. The aim of this study was to investigate expression of Yes-associated protein in lung adenocarcinoma and squamous cell carcinoma. Associations of Yes-associated protein expression with clinicopathologic parameters, expression of cell cycle-specific markers, and epidermal growth factor receptor gene amplification were also analyzed. In a univariate analysis of the 66 adenocarcinomas, high nuclear expression of Yes-associated protein was significantly correlated with expression of cyclin A and mitogen-activated protein kinase. Multivariate analysis, including age and sex, showed that cyclin A expression was independently correlated with nuclear expression of Yes-associated protein in adenocarcinomas. Furthermore, high nuclear expression of Yes-associated protein was also a significant predictor of epidermal growth factor receptor gene amplification for adenocarcinoma. For the 102 squamous cell carcinomas, univariate analysis revealed that high cytoplasmic expression of Yes-associated protein was correlated with the low pathologic TNM staging (stage I) and histologic grading. Multivariate analysis, including age and sex, showed that cytoplasmic expression of Yes-associated protein was an independent predictor of low pathologic TNM staging. These results indicate that nuclear overexpression of Yes-associated protein contributes to pulmonary adenocarcinoma growth and that high cytoplasmic expression of Yes-associated protein is an independent predictor of low pathologic TNM staging and histologic grading. The differential effects of Yes-associated protein expression patterns in adenocarcinomas and squamous cell carcinomas suggest that Yes-associated protein may play important roles in different pathways in distinct tumor subtypes. These observations may, therefore, lead to new perspectives on therapeutic targeting of these tumor

  1. Stereotactic Body Radiation Therapy in Treating Patients With Metastatic Breast Cancer, Non-small Cell Lung Cancer, or Prostate Cancer

    ClinicalTrials.gov

    2016-06-17

    Male Breast Carcinoma; Prostate Adenocarcinoma; Recurrent Breast Carcinoma; Recurrent Non-Small Cell Lung Carcinoma; Recurrent Prostate Carcinoma; Stage IV Breast Cancer; Stage IV Non-Small Cell Lung Cancer; Stage IV Prostate Cancer

  2. TUBERCULOSIS AND LUNG CANCER.

    PubMed

    Tamura, Atsuhisa

    2016-01-01

    The occurrence of pulmonary tuberculosis (PTB) and lung cancer as comorbidities has been extensively discussed in many studies. In the past, it was well known that lung cancer is a specific epidemiological successor of PTB and that lung cancer often develops in scars caused by PTB. In recent years, the relevance of the two diseases has drawn attention in terms of the close epidemiological connection and chronic inflammation-associated carcinogenesis. In Japanese case series studies, most lung cancer patients with tuberculous sequelae received supportive care alone in the past, but more recently, the use of aggressive lung cancer treatment is increasing. Many studies on PTB and lung cancer as comorbidities have revealed that active PTB is noted in 2-5% of lung cancer cases, whereas lung cancer is noted in 1-2% of active PTB cases. In such instances of comorbidity, many active PTB cases showed Type II (non-extensively cavitary disease) and Spread 2-3 (intermediate-extensive diseases) on chest X-rays, but standard anti-tuberculosis treatment easily eradicates negative conversion of sputum culture for M. tuberculosis; lung cancer cases were often stage III- IV and squamous cell carcinoma predominant, and the administration of aggressive treatment for lung cancer is increasing. The major clinical problems associated with PTB and lung cancer as comorbidities include delay in diagnosis (doctor's delay) and therapeutic limitations. The former involves two factors of radiographic interpretation: the principles of parsimony (Occam's razor) and visual search; the latter involves three factors of lung cancer treatment: infectivity of M.tuberculosis, anatomical limitation due to lung damage by tuberculosis, and drug-drug interactions between rifampicin and anti-cancer drugs, especially molecularly targeted drugs. The comorbidity of these two diseases is an important health-related issue in Japan. In the treatment of PTB, the possibility of concurrent lung cancer should be kept

  3. A high vascular count and overexpression of vascular endothelial growth factor are associated with unfavourable prognosis in operated small cell lung carcinoma

    PubMed Central

    Fontanini, G; Faviana, P; Lucchi, M; Boldrini, L; Mussi, A; Camacci, T; Mariani, M A; Angeletti, C A; Basolo, F; Pingitore, R

    2002-01-01

    It has been widely demonstrated that neo-angiogenesis and its mediators (i.e. vascular endothelial growth factor), represent useful indicators of poor prognosis in non small cell lung carcinoma. In order to verify whether neovascularization and vascular endothelial growth factor may be considered useful markers of clinical outcome also in the small cell lung cancer subgroup, we retrospectively investigated a series of 75 patients with small cell lung carcinoma treated by surgery between 1980 and 1990. Immunohistochemically-detected microvessels and vascular endothelial growth factor expressing cells were significantly associated with poor prognosis, as well as with nodal status and pathological stage. In fact, patients whose tumours had vascular count and vascular endothelial growth factor expression higher than median value of the entire series (59 vessels per 0.74 mm2 and 50% of positive cells, respectively), showed a shorter overall and disease-free survival (P=0.001, P=0.001; P=0.008, P=0.03). Moreover, the presence of hilar and/or mediastinal nodal metastasis and advanced stage significantly affected overall and disease-free interval (P=0.00009, P=0.00001; P=0.0001, P=0.00001). At multivariate analysis, only vascular endothelial growth factor expression retained its influence on overall survival (P=0.001), suggesting that angiogenic phenomenon may have an important role in the clinical behaviour of this lung cancer subgroup. British Journal of Cancer (2002) 86, 558–563. DOI: 10.1038/sj/bjc/6600130 www.bjcancer.com © 2002 Cancer Research UK PMID:11870537

  4. Alpha-carotene inhibits metastasis in Lewis lung carcinoma in vitro, and suppresses lung metastasis and tumor growth in combination with taxol in tumor xenografted C57BL/6 mice.

    PubMed

    Liu, Yi-Zhen; Yang, Chih-Min; Chen, Jen-Yin; Liao, Junn-Wang; Hu, Miao-Lin

    2015-06-01

    This study aimed to investigate the anti-metastatic activity of α-carotene (AC) in Lewis lung carcinoma (LLC) and in combination with taxol in LLC-xenografted C57BL/6 mice. Cell culture studies reveal that AC significantly inhibited invasion, migration and activities of matrix metalloproteinase (MMP)-2, -9 and urokinase plasminogen activator but increased protein expression of tissue inhibitor of MMP (TIMP)-1, -2 and plasminogen activator inhibitor (PAI)-1. These effects of AC are similar to those of β-carotene at the same concentration (2.5 μM). AC (2.5 μM) also significantly inhibited integrin β1-mediated phosphorylation of focal adhesion kinase (FAK) which then decreased the phosphorylation of MAPK family. Findings from the animal model reveal that AC treatment (5m g/kg) alone significantly decreased lung metastasis without affecting primary tumor growth, whereas taxol treatment (6 mg/kg) alone exhibited significant inhibition on both actions, as compared to tumor control group. AC treatment alone significantly decreased protein expression of integrin β1 but increased protein expression of TIMP-1 and PAI-1 without affecting protein expression of TIMP-2 and phosphorylation of FAK in lung tissues, whereas taxol treatment alone significantly increased protein expression of TIMP-1, PAI-1 and TIMP-2 but decreased protein expression of integrin β1 and phosphorylation of FAK. The combined treatment produced stronger actions on lung metastasis and lung tissues protein expression of TIMP-1, TIMP-2 and PAI-1. Overall, we demonstrate that AC effectively inhibits LLC metastasis and suppresses lung metastasis in combination with taxol in LLC-bearing mice, suggesting that AC could be used as an anti-metastatic agent or as an adjuvant for anti-cancer drugs.

  5. Phospholipid profiling identifies acyl chain elongation as a ubiquitous trait and potential target for the treatment of lung squamous cell carcinoma

    PubMed Central

    Marien, Eyra; Meister, Michael; Muley, Thomas; del Pulgar, Teresa Gomez; Derua, Rita; Spraggins, Jeffrey M.; Van de Plas, Raf; Vanderhoydonc, Frank; Machiels, Jelle; Binda, Maria Mercedes; Dehairs, Jonas; Willette-Brown, Jami; Hu, Yinling; Dienemann, Hendrik; Thomas, Michael; Schnabel, Philipp A.; Caprioli, Richard M.; Lacal, Juan Carlos; Waelkens, Etienne; Swinnen, Johannes V.

    2016-01-01

    Lung cancer is the leading cause of cancer death. Beyond first line treatment, few therapeutic options are available, particularly for squamous cell carcinoma (SCC). Here, we have explored the phospholipidomes of 30 human SCCs and found that they almost invariably (in 96.7% of cases) contain phospholipids with longer acyl chains compared to matched normal tissues. This trait was confirmed using in situ 2D-imaging MS on tissue sections and by phospholipidomics of tumor and normal lung tissue of the L-IkkαKA/KA mouse model of lung SCC. In both human and mouse, the increase in acyl chain length in cancer tissue was accompanied by significant changes in the expression of acyl chain elongases (ELOVLs). Functional screening of differentially expressed ELOVLs by selective gene knockdown in SCC cell lines followed by phospholipidomics revealed ELOVL6 as the main elongation enzyme responsible for acyl chain elongation in cancer cells. Interestingly, inhibition of ELOVL6 drastically reduced colony formation of multiple SCC cell lines in vitro and significantly attenuated their growth as xenografts in vivo in mouse models. These findings identify acyl chain elongation as one of the most common traits of lung SCC discovered so far and pinpoint ELOVL6 as a novel potential target for cancer intervention. PMID:26862848

  6. Imaging characteristic analysis of metastatic spine lesions from breast, prostate, lung, and renal cell carcinomas for surgical planning: Osteolytic versus osteoblastic

    PubMed Central

    Reddington, Justin A.; Mendez, Gustavo A.; Ching, Alex; Kubicky, Charlotte Dai; Klimo, Paul; Ragel, Brian T.

    2016-01-01

    Background: Surgeons treating metastatic spine disease can use computed tomography (CT) imaging to determine whether lesions are osteolytic, osteoblastic, or mixed. This enables treatment that considers the structural integrity of the vertebral body (VB), which is impaired with lytic lesions but not blastic lesions. The authors analyzed CT imaging characteristics of spine metastasis from breast, lung, prostate, and renal cell carcinomas (RCCs) to determine the metastasis patterns of each of these common tumors. Methods: The authors identified patients with metastatic spine disease treated during a 3-year period. Variables studied included age, sex, and cancer type. Lesions from breast, lung, prostate, and RCC primary lesions were selected for imaging analysis. Results: Sixty-six patients were identified: 17 had breast metastasis, 14 prostate, 18 lung, and 17 RCC. Breast cancer metastasis involved 33% of VBs with 56%, 20%, and 24% osteolytic, osteoblastic, and mixed, respectively. Prostate cancer metastasis involved 35% of VBs with 14%, 62%, and 24% osteolytic, osteoblastic, and mixed, respectively. Lung cancer metastasis involved 13% of VBs with 64%, 33%, and 3% osteolytic, osteoblastic, and mixed, respectively. RCC metastasis involved 11% of VBs with 91%, 7%, and 2% osteolytic, osteoblastic, and mixed lesions, respectively. Conclusions: To improve surgical planning, we advocate the use of CT prior to surgery to evaluate whether spine metastases are osteolytic or osteoblastic. In cases of osteolytic lesions, the concern is of segmental instability requiring reconstruction and the risk for screw pull out should instrumentation be considered. In cases of osteoblastic lesions, surgeons should consider debulking dense bone. PMID:27274410

  7. Mutations and expression of the NFE2L2/KEAP1/CUL3 pathway in Chinese patients with lung squamous cell carcinoma

    PubMed Central

    Zhang, Yongxing; Fan, Hong; Fang, Shuo; Wang, Lin; Chen, Li; Jin, Yulin; Jiang, Wei; Lin, Zongwu; Shi, Yu

    2016-01-01

    Background Recent studies have reported an abnormally high alteration rate in the nuclear factor erythroid 2-like 2 (NFE2L2)/kelch-like ECH-associated protein 1 (KEAP1)/cullin 3 (CUL3) pathway. But the status of this pathway in Chinese patients with lung squamous cell carcinoma (SqCC) has not been thoroughly studied, and there are many uncertainties regarding the expression of pathway intermediates. Methods cDNA sequencing and TaqMan qRT-PCR were carried out in paired cancer and adjacent normal samples obtained from 100 Chinese patients with lung SqCC. Immunohistochemical staining was performed in 50 other paraffin-embedded specimens. Results We detected 47 mutations in 36 patients (36%), and 143 single nucleotide polymorphism (SNP) in 59 patients (59%), of which 41 mutations and 31 SNPs resulted in amino acid (AA) and possibly functional changes. By combining qRT-PCR and immunohistochemistry staining, we confirmed that the expression of NFE2L2 and KEAP1 were highly increased, while the expression of CUL3 was not significantly changed in lung SqCC samples from Chinese patients. Conclusions Considering the frequent mutations and abnormal expression, the NFE2L2/KEAP1/CUL3 pathway may play an important role in the therapy of Chinese patients with lung SqCC. PMID:27499952

  8. PEGylation of paclitaxel largely improves its safety and anti-tumor efficacy following pulmonary delivery in a mouse model of lung carcinoma.

    PubMed

    Luo, Tian; Loira-Pastoriza, Cristina; Patil, Harshad P; Ucakar, Bernard; Muccioli, Giulio G; Bosquillon, Cynthia; Vanbever, Rita

    2016-10-10

    Pulmonary delivery offers an attractive route of administration for chemotherapeutic agents, with the advantages of high drug concentrations locally and low side effects systemically. However, fast clearance mechanisms result in short residence time of small molecule drugs in the lungs. Moreover, the local toxicity induced by antineoplastic drugs is considered a major obstacle for the clinical application of inhaled chemotherapy. In this study, we explored the utility of 6kDa and 20kDa polyethylene glycol-paclitaxel (PEG-PTX) conjugates to retain paclitaxel within the lungs, achieve its sustained release locally, and thereby, improve its efficacy and reduce its pulmonary toxicity. The conjugates increased the maximum tolerated dose of paclitaxel by up to 100-fold following intratracheal instillation in healthy mice. PEG-PTX conjugates induced lung inflammation. However, the inflammation was lower than that induced by an equivalent dose of the free drug and it was reversible. Conjugation of paclitaxel to both PEG sizes significantly enhanced its anti-tumor efficacy following intratracheal instillation of a single dose in a Lewis lung carcinoma model in mice. PEG-PTX 20k showed equivalent efficacy as PEG-PTX 6k delivered at a 2.5-fold higher dose, suggesting that the molecular weight of the conjugate plays a role in anti-cancer activity. PEG-PTX 20k conjugate presented a prolonged residency and a sustained paclitaxel release within the lungs. This study showed that PEGylation of paclitaxel offers a potential delivery system for inhalation with improved anti-cancer efficacy, prolonged exposure of lung-resident tumors to the antineoplastic drug and reduced local toxicity. PMID:27515664

  9. LUMOR: an app for standardized control and monitoring of a porcine lung and its nutrient cycle.

    PubMed

    Lenz, Gregor; Frohner, Matthias; Sauermann, Stefan; Forjan, Mathias

    2014-01-01

    The outcome of the EU-funded project ElBik has been the lung simulator 'iLung', which imitates an actively breathing human lung with a porcine lung. In order to keep the explanted lung in a nearly physiological state during transportation from the slaughterhouse to the ventilation laboratory the tissue needs to be nourished and temperature controlled. The Project AlveoPic designs a mobile transport vehicle implementing an ISO/IEEE 11073-20601 compliant communication interface for the exchange of the physical parameters, alert messages and setpoint-values. An appropriate 11073 domain information model is designed and limitations of the defined services and attributes are identified. For monitoring purposes the Android App LUMOR is implemented providing a user with an easy-to-handle GUI. It was found, that alert capabilities and remote set features are not well supported in ISO/IEEE 11073-20601 at the moment and possible workarounds are discussed. PMID:24825688

  10. Induction of COX-2 protein expression by vanadate in A549 human lung carcinoma cell line through EGF receptor and p38 MAPK-mediated pathway

    SciTech Connect

    Chien, P.-S.; Mak, O.-T.; Huang, H.-J. . E-mail: haojen@mail.ncku.edu.tw

    2006-01-13

    Vanadate is a transition metal widely distributed in the environment. It has been reported that vanadate associated with air pollution particles can modify DNA synthesis, causing cell growth arrest, and apoptosis. Moreover, vanadium exposure was also found to cause the synthesis of inflammatory cytokines, such as interleukin-1, tumor necrosis factor-{alpha}, and prostaglandin E{sub 2}. Here, we found that exposure of A549 human lung carcinoma cells to vanadate led to extracellular signal-regulated kinase, c-Jun NH{sub 2}-terminal protein kinases (JNKs), p38 mitogen-activated protein kinase (p38) activation, and COX-2 protein expression in a dose-dependent manner. SB203580, a p38 MAPK inhibitor, but not PD098059 and SP600125, specific inhibitor of MKK1 and selective inhibitor of JNK, respectively, suppressed COX-2 expression. Furthermore, the epithelial growth factor (EGF) receptor specific inhibitor (PD153035) reduced vanadate-induced COX-2 expression. However, scavenging of vanadate-induced reactive oxygen species by catalase, a specific H{sub 2}O{sub 2} inhibitor, or DPI, an NADPH oxidase inhibitor, resulted in no inhibition on COX-2 expression. Together, we suggested that EGF receptor and p38 MAPK signaling pathway may be involved in vanadate-induced COX-2 protein expression in A549 human lung carcinoma cell line.

  11. Apoptotic potential of C-phycoerythrin from Phormidium sp. A27DM and Halomicronema sp. A32DM on human lung carcinoma cells.

    PubMed

    Madamwar, Datta; Patel, Dipak K; Desai, Swati N; Upadhyay, Kapil K; Devkar, Ranjitsinh V

    2015-01-01

    Phycobilisomes present in cyanobacteria are photosynthetic macromolecular protein complexes that are categorized into three types - phycoerythrins (high energy), phycocyanin (intermediate energy) and allophycocyanin (low energy). Structurally, they consist of α and β protein subunits and open chain tetrapyrrole prosthetic group (bilin chromophore), known for its antioxidant properties and therapeutic potential against a variety of physiological ailments. Phycoerythrins (C-PE) were purified from cyanobacterial strains Phormidium sp. A27DM and Halomicronema sp. A32DM and their respective apoptotic potentials were assessed on A549 human lung carcinoma cells. Both strains of cyanobacteria were cultured and the C-PE from each strain was extracted, quantified and characterized. C-PE accounted for a dose dependent decrement in cell viability, mitochondrial membrane potential and an increment in lactate dehydrogenase release. Higher doses of C-PE (of both strains) accounted for loss of cell viability and nuclear pycnosis. These findings were further substantiated with flow cytometry that revealed a cell arrest at G0/G1 phase and a high percentage of cells undergoing apoptosis following C-PE treatment. These results confirm the efficacy of C-PE from Phormidium sp. or Halomicronema sp. in triggering apoptotic cell death. This study is the first to report on apoptotic property of C-PE against A549 human lung carcinoma cells and warrants further studies to establish its anti-cancer potential. PMID:26535041

  12. Inonotus obliquus-derived polysaccharide inhibits the migration and invasion of human non-small cell lung carcinoma cells via suppression of MMP-2 and MMP-9.

    PubMed

    Lee, Ki Rim; Lee, Jong Seok; Song, Jeong Eun; Ha, Suk Jin; Hong, Eock Kee

    2014-12-01

    Polysaccharides isolated from the fruiting body of Inonotus obliquus (PFIO) are known to possess various pharmacological properties including antitumor activity. However, the anti-metastatic effect and its underlying mechanistic signaling pathway involved these polysaccharides in human non-small cell lung carcinoma remain unknown. The present study therefore aimed to determine the anti-metastatic potential and signaling pathways of PFIO in the highly metastatic A549 cells. We found that PFIO suppressed the migration and invasive ability of A549 cells while decreasing the expression levels and activity of matrix metalloproteinase (MMP)-2 and MMP-9. Furthermore, PFIO decreased the phosphorylation levels of mitogen-activated protein kinases (MAPKs) and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) as well as the expression level of COX-2, and inhibited the nuclear translocation of nuclear factor κB (NF-κB) in A549 cells. These results suggested that PFIO could suppress the invasion and migration of human lung carcinoma by reducing the expression levels and activity of MMP-2 and MMP-9 via suppression of MAPKs, PI3K/AKT, and NF-κB signaling pathways.

  13. Apoptotic potential of C-phycoerythrin from Phormidium sp. A27DM and Halomicronema sp. A32DM on human lung carcinoma cells

    PubMed Central

    Madamwar, Datta; Patel, Dipak K; Desai, Swati N; Upadhyay, Kapil K; Devkar, Ranjitsinh V

    2015-01-01

    Phycobilisomes present in cyanobacteria are photosynthetic macromolecular protein complexes that are categorized into three types - phycoerythrins (high energy), phycocyanin (intermediate energy) and allophycocyanin (low energy). Structurally, they consist of α and β protein subunits and open chain tetrapyrrole prosthetic group (bilin chromophore), known for its antioxidant properties and therapeutic potential against a variety of physiological ailments. Phycoerythrins (C-PE) were purified from cyanobacterial strains Phormidium sp. A27DM and Halomicronema sp. A32DM and their respective apoptotic potentials were assessed on A549 human lung carcinoma cells. Both strains of cyanobacteria were cultured and the C-PE from each strain was extracted, quantified and characterized. C-PE accounted for a dose dependent decrement in cell viability, mitochondrial membrane potential and an increment in lactate dehydrogenase release. Higher doses of C-PE (of both strains) accounted for loss of cell viability and nuclear pycnosis. These findings were further substantiated with flow cytometry that revealed a cell arrest at G0/G1 phase and a high percentage of cells undergoing apoptosis following C-PE treatment. These results confirm the efficacy of C-PE from Phormidium sp. or Halomicronema sp. in triggering apoptotic cell death. This study is the first to report on apoptotic property of C-PE against A549 human lung carcinoma cells and warrants further studies to establish its anti-cancer potential. PMID:26535041

  14. Large, central acellular zones indicating myoepithelial tumor differentiation in high-grade invasive ductal carcinomas as markers of predisposition to lung and brain metastases.

    PubMed

    Tsuda, H; Takarabe, T; Hasegawa, F; Fukutomi, T; Hirohashi, S

    2000-02-01

    High-grade invasive ductal carcinomas (IDCs) of the breast with large, central acellular zones on their cut surfaces are usually associated with the myoepithelial immunophenotype of carcinoma cells, which includes the expression of S-100 protein, alpha-smooth muscle actin, and keratin 14. To clarify the clinical significance of these features of IDCs, the authors compared the incidence of the myoepithelial immunophenotype immunohistochemically, patient prognosis, and metastatic sites of the tumor between 20 high-grade IDCs with large, central acellular zones and 40 control high-grade IDCs without these zones. The myoepithelial immunophenotype was detected in 16 IDCs (80%) with large, central acellular zones but in only seven IDCs (18%) without. The risk ratio of metastasis, especially in the brain and lung, and death from cancer were significantly higher (p = 0.0096 and p = 0.030) for the 20 IDCs with large, central acellular zones than for those without by Cox's univariate analysis. Using Cox's multivariate analysis, large, central acellular zones in IDCs were an indicator of high risk of brain and lung metastases and of death by cancer independent of nodal status and tumor size. Examination of large, central acellular zones and myoepithelial immunophenotype in high-grade IDCs appears helpful in predicting patient prognosis and preferential metastatic sites of the tumors.

  15. Misonidazole combined with radiotherapy in the treatment of inoperable squamous cell carcinoma of the lung. A double-blind randomized trial

    SciTech Connect

    Panduro, J.; Kjaer, M.; Wolff-Jensen, J.; Hansen, H.H.

    1983-07-01

    Sixty-seven patients with inoperable squamous cell carcinoma of the lung were randomized to receive split-course irradiation therapy, 40 Gy in 10 fractions over 5 weeks plus either placebo or misonidazole 1.200 mg/m2 orally on each treatment day. The target area was the primary tumor, both hilar regions, mediastinum, and both supraclavicular regions. Thirty-three patients received misonidazole, while 34 patients received placebo. Mean observation time for the study was 27 months (range, 17-36+ months. 31% of the patients in the misonidazole group obtained a complete response (CR) or a partial response (PR) as compared to 29% in the placebo group. No difference was demonstrated in the relapse pattern comparing the two groups. The death intensity was significantly higher (P . 0.03) in the misonidazole than in the placebo group, with the median survival being 4.2 and 6.7 months, respectively. Eight patients in the misonidazole group (31%) developed sensoric neuropathy while one patient in the placebo group developed irradiation myelopathy of the Brown-Sequard type. The group of patients who later developed neuropathy had significantly higher plasma misonidazole concentrations on treatment days than the group of patients who did not. It is concluded that the combination of misonidazole and irradiation therapy for inoperable squamous cell carcinoma of the lung has no effect on response rate and relapse pattern, but a significant unexplained adverse effect on survival.

  16. The targeted inhibitory effects of human amniotic fluid stem cells carrying CXCR4 promoter and DAL-1 on non-small cell lung carcinoma growth.

    PubMed

    Li, L; Li, S; Cai, T; Wang, H; Xie, X; Liu, Z; Zhang, Y

    2016-02-01

    The differentially expressed in adenocarcinoma of the lung-1 (DAL-1) protein has been demonstrated to be suppressive to various types of tumors including lung cancer. This study aimed to determine the targeted effects of human amniotic fluid stem cells (hAFS cells) carrying CXCR4 promoter driven conditionally replicable adenovirus vector overexpressing DAL-1 (Ad-CXCR4-DAL-1) on non-small cell lung carcinoma (NSCLC) growth. The apoptotic effects of virus vectors were assessed using flow cytometry, and the cytotoxicity analyzed by CCK-8 assay. In vivo imaging system was used to determine the homing capability of hAFS cells. A549 cell xenograft mouse model was created to assess the in vivo effect of DAL-1 overexpression on NSCLC growth. We found that infection of Ad-CXCR4-DAL-1 increased the apoptosis of A549 NSCLC cells but not 16HBE normal human bronchial epithelial cells. Ad-CXCR4-DAL-1 administered via intratumoral injection led to significant reduced growth and greater necrosis of A549 xenograft tumors comparing to null vector treated animals. When infused via tail vein, hAFS cells carrying Ad-CXCR4-DAL-1 homed to lung cancer xenografts, caused virus replication and DAL-1 overexpression, and led to significant lower growth and greater necrosis of A549 cell xenografts comparing to non-treatment control. In conclusion, hAFS cells are capable of carrying Ad-CXCR4-DAL-1 vectors, specifically targeting to lung cancer, and causing oncolytic effects when administered in vivo.

  17. The role of Rac1 in the regulation of NF-kB activity, cell proliferation, and cell migration in non-small cell lung carcinoma

    PubMed Central

    Gastonguay, Adam; Berg, Tracy; Hauser, Andrew D.; Schuld, Nathan; Lorimer, Ellen; Williams, Carol L.

    2012-01-01

    The small GTPase Rac1 regulates many cellular processes, including cytoskeletal reorganization, cell migration, proliferation, and survival. Additionally, Rac1 plays a major role in activating NF-κB-mediated transcription. Both Rac1 and NF-κB regulate many properties of the malignant phenotype, including anchorage-independent proliferation and survival, metastasis, and angiogenesis. Despite these findings, the roles of Rac1and NF-κB in non-small cell lung carcinoma, a leading cause of cancer deaths, have not been thoroughly investigated. Here, we compared the effects of Rac1 siRNA to that of the Rac1 inhibitor NSC23766 on multiple features of the NSCLC malignant phenotype, including NF-κB activity. We show that the siRNA-mediated silencing of Rac1 in lung cancer cells results in decreased cell proliferation and migration. The decrease in proliferation was observed in both anchorage-dependent and anchorage-independent assays. Furthermore, cells with decreased Rac1 expression have a slowed progression through the G1 phase of the cell cycle. These effects induced by Rac1 siRNA correlated with a decrease in NF-κB transcriptional activity. Additionally, inhibition of NF-κB signaling with BAY 11–7082 inhibited proliferation; indicating that the loss of cell proliferation and migration induced by the silencing of Rac1 expression may be attributed in part to loss of NF-κB activity. Interestingly, treatment with the Rac1 inhibitor NSC23766 strongly inhibits cell proliferation, cell cycle progression, and NF-κB activity in lung cancer cells, to an even greater extent than the inhibition induced by Rac1 siRNA. These findings indicate that Rac1 plays an important role in lung cancer cell proliferation and migration, most likely through its ability to promote NF-κB activity, and highlight Rac1 pathways as therapeutic targets for the treatment of lung cancer. PMID:22549160

  18. The role of Rac1 in the regulation of NF-κB activity, cell proliferation, and cell migration in non-small cell lung carcinoma.

    PubMed

    Gastonguay, Adam; Berg, Tracy; Hauser, Andrew D; Schuld, Nathan; Lorimer, Ellen; Williams, Carol L

    2012-06-01

    The small GTPase Rac1 regulates many cellular processes, including cytoskeletal reorganization, cell migration, proliferation, and survival. Additionally, Rac1 plays a major role in activating NF-κB-mediated transcription. Both Rac1 and NF-κB regulate many properties of the malignant phenotype, including anchorage-independent proliferation and survival, metastasis, and angiogenesis. Despite these findings, the roles of Rac1and NF-κB in non-small cell lung carcinoma, a leading cause of cancer deaths, have not been thoroughly investigated. Here, we compared the effects of Rac1 siRNA to that of the Rac1 inhibitor NSC23766 on multiple features of the NSCLC malignant phenotype, including NF-κB activity. We show that the siRNA-mediated silencing of Rac1 in lung cancer cells results in decreased cell proliferation and migration. The decrease in proliferation was observed in both anchorage-dependent and anchorage-independent assays. Furthermore, cells with decreased Rac1 expression have a slowed progression through the G 1 phase of the cell cycle. These effects induced by Rac1 siRNA correlated with a decrease in NF-κB transcriptional activity. Additionally, inhibition of NF-κB signaling with BAY 11-7082 inhibited proliferation; indicating that the loss of cell proliferation and migration induced by the silencing of Rac1 expression may be attributed in part to loss of NF-κB activity. Interestingly, treatment with the Rac1 inhibitor NSC23766 strongly inhibits cell proliferation, cell cycle progression, and NF-κB activity in lung cancer cells, to an even greater extent than the inhibition induced by Rac1 siRNA. These findings indicate that Rac1 plays an important role in lung cancer cell proliferation and migration, most likely through its ability to promote NF-κB activity, and highlight Rac1 pathways as therapeutic targets for the treatment of lung cancer.

  19. Defining a standard set of patient-centred outcomes for lung cancer

    PubMed Central

    van Bommel, Annelotte C.M.; Stowell, Caleb; Abrahm, Janet L.; Baker, Matthew; Baldotto, Clarissa S.; Baldwin, David R.; Borthwick, Diana; Carbone, David P.; Chen, Aileen B.; Fox, Jesme; Haswell, Tom; Koczywas, Marianna; Kozower, Benjamin D.; Mehran, Reza J.; Schramel, Franz M.; Senan, Suresh; Stirling, Robert G.; van Meerbeeck, Jan P.; Wouters, Michel W.J.M.

    2016-01-01

    In lung cancer, outcome measurement has been mostly limited to survival. Proper assessment of the value of lung cancer treatments, and the performance of institutions delivering care, requires more comprehensive measurement of standardised outcomes. The International Consortium for Health Outcomes Measurement convened an international, multidisciplinary working group of patient representatives, medical oncologists, surgeons, radiation oncologists, pulmonologists, palliative care specialists, registry experts and specialist nurses to review existing data and practices. Using a modified Delphi method, the group developed a consensus recommendation (“the set”) on the outcomes most essential to track for patients with lung cancer, along with baseline demographic, clinical and tumour characteristics (case-mix variables) for risk adjustment. The set applies to patients diagnosed with nonsmall cell lung cancer and small cell lung cancer. Our working group recommends the collection of the following outcomes: survival, complications during or within 6 months of treatment and patient-reported domains of health-related quality of life including pain, fatigue, cough and dyspnoea. Case-mix variables were defined to improve interpretation of comparisons. We defined an international consensus recommendation of the most important outcomes for lung cancer patients, along with relevant case-mix variables, and are working to support adoption and reporting of these measures globally. PMID:27390281

  20. Defining a standard set of patient-centred outcomes for lung cancer.

    PubMed

    Mak, Kimberley S; van Bommel, Annelotte C M; Stowell, Caleb; Abrahm, Janet L; Baker, Matthew; Baldotto, Clarissa S; Baldwin, David R; Borthwick, Diana; Carbone, David P; Chen, Aileen B; Fox, Jesme; Haswell, Tom; Koczywas, Marianna; Kozower, Benjamin D; Mehran, Reza J; Schramel, Franz M; Senan, Suresh; Stirling, Robert G; van Meerbeeck, Jan P; Wouters, Michel W J M; Peake, Michael D

    2016-09-01

    In lung cancer, outcome measurement has been mostly limited to survival. Proper assessment of the value of lung cancer treatments, and the performance of institutions delivering care, requires more comprehensive measurement of standardised outcomes.The International Consortium for Health Outcomes Measurement convened an international, multidisciplinary working group of patient representatives, medical oncologists, surgeons, radiation oncologists, pulmonologists, palliative care specialists, registry experts and specialist nurses to review existing data and practices. Using a modified Delphi method, the group developed a consensus recommendation ("the set") on the outcomes most essential to track for patients with lung cancer, along with baseline demographic, clinical and tumour characteristics (case-mix variables) for risk adjustment.The set applies to patients diagnosed with nonsmall cell lung cancer and small cell lung cancer. Our working group recommends the collection of the following outcomes: survival, complications during or within 6 months of treatment and patient-reported domains of health-related quality of life including pain, fatigue, cough and dyspnoea. Case-mix variables were defined to improve interpretation of comparisons.We defined an international consensus recommendation of the most important outcomes for lung cancer patients, along with relevant case-mix variables, and are working to support adoption and reporting of these measures globally. PMID:27390281

  1. [Complete Surgical Resection of a Huge Hepatocellular Carcinoma Invading the Diaphragm and Lung after Transcatheter Arterial Chemoembolization (TACE) and Sorafenib--A Case Report].

    PubMed

    Mukai, Yosuke; Wada, Hiroshi; Eguchi, Hidetoshi; Tomokuni, Akira; Tomimaru, Yoshito; Asaoka, Tadafumi; Kawamoto, Koichi; Marubashi, Shigeru; Umeshita, Koji; Doki, Yuichiro; Mori, Masaki; Nagano, Hiroaki

    2015-11-01

    We report a case of locally advanced huge hepatocellular carcinoma (HCC) invading the diaphragm and the right lung, which was controlled by sorafenib, thereby allowing curative resection. A 72-year-old man was diagnosed with advanced HCC invading the diaphragm and the right lung. At the time of diagnosis, his tumor was considered unresectable and he underwent transarterial embolization (TAE)/transcatheter arterial chemoembolization (TACE) 3 times. Assessment with enhanced CT after TAE/TACE showed that a viable lesion remained. Subsequently, he was treated with sorafenib for 15 months. Reassessment showed that the main tumor remained stable in size, and he was admitted to our hospital for surgery. Preoperative evaluation by enhanced CT and MRI detected an intrahepatic metastasis in segment 4 of the liver. After TACE was performed for this nodule, extended right hemihepatectomy with right diaphragmatic and right lung partial resection was performed. He had no postoperative complications and was discharged 27 days after surgery. He remains alive without recurrence 10 months after surgery. PMID:26805122

  2. A Series of α-Amino Acid Ester Prodrugs of Camptothecin: In vitro Hydrolysis and A549 Human Lung Carcinoma Cell Cytotoxicity

    PubMed Central

    Deshmukh, Manjeet; Chao, Piyun; Kutscher, Hilliard L.; Gao, Dayuan; Sinko, Patrick J.

    2013-01-01

    The objective of the present study was to identify a camptothecin (CPT) prodrug with optimal release and cytotoxicity properties for immobilization on a passively targeted microparticle delivery system. A series of α-amino acid ester prodrugs of CPT were synthesized, characterized and evaluated. Four CPT prodrugs were synthesized with increasing aliphatic chain length (glycine (Gly) (2a), alanine (Ala) (2b), aminobutyric acid (Abu) (2c) and norvaline (Nva) (2d)). Prodrug reconversion was studied at pH 6.6, 7.0 and 7.4 corresponding to tumor, lung and extracellular/physiological pH, respectively. Cytotoxicity was evaluated in A549 human lung carcinoma cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The hydrolytic reconversion rate to parent CPT increased with decreasing side chain length as well as increasing pH. The Hill slope of 2d was significantly less than CPT and the other prodrugs tested, indicating a higher cell death rate at lower concentrations. These results suggest that 2d is the best candidate for a passively targeted sustained release lung delivery system. PMID:20063889

  3. Multicenter Phase II Study of Nedaplatin and Irinotecan for Patients with Squamous Cell Carcinoma of the Lung: Thoracic Oncology Research Group 0910.

    PubMed

    Yamada, Kouzo; Saito, Haruhiro; Kondo, Tetsuro; Murakami, Shuji; Masuda, Noriyuki; Yamamoto, Michiko; Igawa, Satoshi; Katono, Ken; Takiguchi, Yuichi; Iwasawa, Shunichiro; Kurimoto, Ryota; Okamoto, Hiroaki; Shimokawa, Tsuneo; Hosomi, Yukio; Takagi, Yusuke; Kishi, Kazuma; Ohba, Mari; Oshita, Fumihiro; Watanabe, Koshiro

    2015-12-01

    Squamous cell carcinoma (SCC) of the lung is moderately responsive to anticancer drugs, but no specific chemotherapy regimens have yet been established. We conducted a multicenter phase II study of nedaplatin (NP) and irinotecan (CPT) for SCC of the lung. Fifty patients underwent 4 to 6 cycles of chemotherapy comprising of NP at 100 mg/m(2) on day 1 and CPT at 60 mg/m(2) on days 1 and 8 every 4 weeks. Twenty-seven patients received 4 to 6 cycles of chemotherapy (median=4 cycles). Major toxicities included neutropenia (46.0%), grade 3 or 4 anorexia (22.0%), febrile neutropenia (16.0%), diarrhea (12.0%), hyponatremia (12.0%), grade 4 anemia (10.0%), thrombocytopenia (10.0%) and infection (10.0%). There were no treatment-related deaths. One patient achieved a complete response and 16 a partial response, with an overall response rate of 34.0%. The median survival time was 11.8 months (95% CI=8.3-15.8 months) and the 2-year survival rate was 22.0%. In conclusion, the NP and CPT regimen is not recommend for further evaluation for patients with advanced SCC of the lung. PMID:26637886

  4. A Phase II Clinical Trial of CPI-613 in Patients with Relapsed or Refractory Small Cell Lung Carcinoma

    PubMed Central

    Pardee, Timothy S.; Petty, William J.; Bonomi, Marcelo; Alistar, Angela; Lamar, Zanetta S.; Isom, Scott; Chan, Michael D.; Miller, Antonius A.; Ruiz, Jimmy

    2016-01-01

    Background Small cell lung cancer (SCLC) is a common lung cancer which presents with extensive stage disease at time of diagnosis in two-thirds of patients. For treatment of advanced disease, traditional platinum doublet chemotherapy induces response rates up to 80% but with few durable responses. CPI-613 is a novel anti-cancer agent that selectively inhibits the altered form of mitochondrial energy metabolism in tumor cells. Methods We evaluated CPI-613 with a single-arm, open-label phase II study in patients with relapsed or refractory SCLC. CPI-613 was given at a dose of 3,000 mg/m2 on days 1 and 4 of weeks 1–3 of 4 week cycle. The primary outcome was response rate as assessed by CT imaging using RECIST v1.1 criteria. Secondary outcomes were progression-free survival (PFS), overall survival (OS), and toxicity. Twelve patients were accrued (median age 57yo) who had previously received between 1 and 4 lines of chemotherapy (median 1) for SCLC with a treatment-free interval of less than 60 days in 9 of the 12 patients. Results No complete or partial responses were seen. Ten patients (83%) progressed as best response and 2 (17%) were not evaluable for response. Median time to progression was 1.7 months (range 0.7 to 1.8 months). Eleven patients (92%) died with median overall survival of 4.3 months (range 1.2 to 18.2 months). The study was closed early due to lack of efficacy. Of note, three out of three patients who progressed after CPI-613 and were subsequently treated with standard topotecan then demonstrated treatment response with survival for 18.2, 7.4, and 5.1 months. We conducted laboratory studies which found synergy in-vitro for CPI-613 with topotecan. Conclusions Single agent CPI-613 had no efficacy in this study. Further study of CPI 613 in combination with a topoisomerase inhibitor is warranted. PMID:27732654

  5. K-RAS MUTATIONS IN LUNG CARCINOMAS FROM NONSMOKING WOMEN EXPOSED TO UNVENTED COAL SMOKE IN CHINA

    EPA Science Inventory

    Abstract Lung cancer mortality rate in nonsmoking women in Xuan Wei (XW) County is the highest in China. The XW lung cancer rate is associated with exposure to coal smoke, containing high concentrations of polycyclic aromatic hydrocarbons (PARs), in unvented homes. Here we restig...

  6. Is the shape of the decline in risk following quitting smoking similar for squamous cell carcinoma and adenocarcinoma of the lung? A quantitative review using the negative exponential model.

    PubMed

    Fry, John S; Lee, Peter N; Forey, Barbara A; Coombs, Katharine J

    2015-06-01

    One possible contributor to the reported rise in the ratio of adenocarcinoma to squamous cell carcinoma of the lung may be differences in the pattern of decline in risk following quitting for the two lung cancer types. Earlier, using data from 85 studies comparing overall lung cancer risks in current smokers, quitters (by time quit) and never smokers, we fitted the negative exponential model, deriving an estimate of 9.93years for the half-life - the time when the excess risk for quitters compared to never smokers becomes half that for continuing smokers. Here we applied the same techniques to data from 16 studies providing RRs specific for lung cancer type. From the 13 studies where the half-life was estimable for each type, we derived estimates of 11.68 (95% CI 10.22-13.34) for squamous cell carcinoma and 14.45 (11.92-17.52) for adenocarcinoma. The ratio of the half-lives was estimated as 1.32 (95% CI 1.20-1.46, p<0.001). The slower decline in quitters for adenocarcinoma, evident in subgroups by sex, age and other factors, may be one of the factors contributing to the reported rise in the ratio of adenocarcinoma to squamous cell carcinoma. Others include changes in the diagnosis and classification of lung cancer.

  7. Ultrasound of extravascular lung water: a new standard for pulmonary congestion

    PubMed Central

    Picano, Eugenio; Pellikka, Patricia A.

    2016-01-01

    Extravascular lung water (EVLW) is a key variable in heart failure management and prognosis, but its objective assessment remains elusive. Lung imaging has been traditionally considered off-limits for ultrasound techniques due to the acoustic barrier of high-impedance air wall. In pulmonary congestion however, the presence of both air and water creates a peculiar echo fingerprint. Lung ultrasound shows B-lines, comet-like signals arising from a hyper-echoic pleural line with a to-and-fro movement synchronized with respiration. Increasing EVLW accumulation changes the normal, no-echo signal (black lung, no EVLW) into a black-and-white pattern (interstitial sub-pleural oedema with multiple B-lines) or a white lung pattern (alveolar pulmonary oedema) with coalescing B-lines. The number and spatial extent of B-lines on the antero-lateral chest allows a semi-quantitative estimation of EVLW (from absent, ≤5, to severe pulmonary oedema, >30 B-lines). Wet B-lines are made by water and decreased by diuretics, which cannot modify dry B-lines made by connective tissue. B-lines can be evaluated anywhere (including extreme environmental conditions with pocket size instruments to detect high-altitude pulmonary oedema), anytime (during dialysis to titrate intervention), by anyone (even a novice sonographer after 1 h training), and on anybody (since the chest acoustic window usually remains patent when echocardiography is not feasible). Cardiologists can achieve much diagnostic gain with little investment of technology, training, and time. B-lines represent ‘the shape of lung water’. They allow non-invasive detection, in real time, of even sub-clinical forms of pulmonary oedema with a low cost, radiation-free approach. PMID:27174289

  8. Systems for Lung Volume Standardization during Static and Dynamic MDCT-based Quantitative Assessment of Pulmonary Structure and Function

    PubMed Central

    Fuld, Matthew K.; Grout, Randall; Guo, Junfeng; Morgan, John H.; Hoffman, Eric A.

    2013-01-01

    Rationale and Objectives Multidetector-row Computed Tomography (MDCT) has emerged as a tool for quantitative assessment of parenchymal destruction, air trapping (density metrics) and airway remodeling (metrics relating airway wall and lumen geometry) in chronic obstructive pulmonary disease (COPD) and asthma. Critical to the accuracy and interpretability of these MDCT-derived metrics is the assurance that the lungs are scanned during a breath-hold at a standardized volume. Materials and Methods A computer monitored turbine-based flow meter system was developed to control patient breath-holds and facilitate static imaging at fixed percentages of the vital capacity. Due to calibration challenges with gas density changes during multi-breath xenon-CT an alternative system was required. The design incorporated dual rolling seal pistons. Both systems were tested in a laboratory environment and human subject trials. Results The turbine-based system successfully controlled lung volumes in 32/37 subjects, having a linear relationship for CT measured air volume between repeated scans: for all scans, the mean and confidence interval of the differences (scan1-scan2) was −9 ml (−169, 151); for TLC alone 6 ml (−164, 177); for FRC alone, −23 ml (−172, 126). The dual-piston system successfully controlled lung volume in 31/41 subjects. Study failures related largely to subject non-compliance with verbal instruction and gas leaks around the mouthpiece. Conclusion We demonstrate the successful use of a turbine-based system for static lung volume control and demonstrate its inadequacies for dynamic xenon-CT studies. Implementation of a dual-rolling seal spirometer has been shown to adequately control lung volume for multi-breath wash-in xenon-CT studies. These systems coupled with proper patient coaching provide the tools for the use of CT to quantitate regional lung structure and function. The wash-in xenon-CT method for assessing regional lung function, while not

  9. Tobacco carcinogen induces both lung cancer and non-alcoholic steatohepatitis and hepatocellular carcinomas in ferrets which can be attenuated by lycopene supplementation.

    PubMed

    Aizawa, Koichi; Liu, Chun; Tang, Sanyuan; Veeramachaneni, Sudipta; Hu, Kang-Quan; Smith, Donald E; Wang, Xiang-Dong

    2016-09-01

    Early epidemiologic studies have reported that tobacco smoking, which is causally associated with liver cancer, is an independent risk factor for non-alcoholic fatty liver diseases (NAFLD). Lycopene from tomatoes has been shown to be a potential preventive agent against NAFLD and hepatocellular carcinoma (HCC). In the present study, we investigated whether the tobacco carcinogen 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induces lesions in both lungs and livers of ferrets with or without lycopene intervention. Male ferrets (6 groups, n = 8-10) were treated either with NNK (50 mg/kg BW, i.p., once a month for four consecutive months) or saline with or without dietary lycopene supplementation (2.2 and 6.6 mg/kg BW/day, respectively) for 26 weeks. Results demonstrate that NNK exposure results in higher incidences of lung tumors, HCC and steatohepatitis (which is characterized by severe inflammatory cell infiltration with concurrent fat accumulation in liver, hepatocellular ballooning degeneration and increased NF-κB expression), as well as elevations in bilirubin and AST levels in ferrets. Lycopene supplementation at two doses prevented NNK-induced expressions of α7 nicotinic acetylcholine receptor in the lung and NF-κB and CYP2E1 in the liver and attenuated the NNK-induced mortality and pathological lesions in both the lungs and livers of ferrets. The present study provided strong experimental evidence that the tobacco carcinogen NNK can induce both HCC and steatohepatitis in the ferrets and can be a useful model for studying tobacco carcinogen-associated NAFLD and liver cancer. Furthermore, lycopene could provide potential benefits against smoke carcinogen-induced pulmonary and hepatic injury. PMID:27116542

  10. TM4SF4 overexpression in radiation-resistant lung carcinoma cells activates IGF1R via elevation of IGF1.

    PubMed

    Choi, Soo-Im; Kim, Seo-Yeon; Lee, Jaeha; Cho, Eun-Wie; Kim, In-Gyu

    2014-10-30

    Transmembrane 4 L six family member 4 (TM4SF4) is a member of the tetraspanin L6 domain family. Other members of this family, TM4SF1 (also known as L6-Ag) and TM4SF5, have been shown to be upregulated in multiple tumors and involved in epithelial-to-mesenchymal transition and cell migration. However, unlike its homologs, little is known about TM4SF4. Here, we show that TM4SF4 was highly expressed in radiation-resistant lung adenocarcinoma cells, such as A549 and Calu-3 cells, and its expression activated cell growth, migration, and invasion. Overexpression of TM4SF4 in A549 cells increased the activation of PI3K, AKT, and NF-kappaB and the expression of PTEN. IGF1R was clearly activated by overexpression of TM4SF4, although EGFR was also slightly activated. TM4SF4 expression was correlated with the increased expression of IGF1, consequently resulting in IGF1R activation. Tumorigenic activity of TM4SF4 in lung adenocarcinoma cells was also demonstrated by xenograft assay; however, this activity was almost completely suppressed by treatment with anti-TM4SF4 antibody. Our results suggest that TM4SF4 overexpression in lung carcinoma cells results in resistance to radiotherapy via IGF1-induced IGF1R activation and blocking the activity of TM4SF4 using specific antibody can be a promising therapeutics against TM4SF4-overexpressing lung adenocarcinoma. PMID:25344917

  11. TM4SF4 overexpression in radiation-resistant lung carcinoma cells activates IGF1R via elevation of IGF1

    PubMed Central

    Choi, Soo-Im; Kim, Seo-Yeon; Lee, Jaeha; Cho, Eun-Wie; Kim, In-Gyu

    2014-01-01

    Transmembrane 4 L six family member 4 (TM4SF4) is a member of the tetraspanin L6 domain family. Other members of this family, TM4SF1 (also known as L6-Ag) and TM4SF5, have been shown to be upregulated in multiple tumors and involved in epithelial-to-mesenchymal transition and cell migration. However, unlike its homologs, little is known about TM4SF4. Here, we show that TM4SF4 was highly expressed in radiation-resistant lung adenocarcinoma cells, such as A549 and Calu-3 cells, and its expression activated cell growth, migration, and invasion. Overexpression of TM4SF4 in A549 cells increased the activation of PI3K, AKT, and NF-kappaB and the expression of PTEN. IGF1R was clearly activated by overexpression of TM4SF4, although EGFR was also slightly activated. TM4SF4 expression was correlated with the increased expression of IGF1, consequently resulting in IGF1R activation. Tumorigenic activity of TM4SF4 in lung adenocarcinoma cells was also demonstrated by xenograft assay; however, this activity was almost completely suppressed by treatment with anti-TM4SF4 antibody. Our results suggest that TM4SF4 overexpression in lung carcinoma cells results in resistance to radiotherapy via IGF1-induced IGF1R activation and blocking the activity of TM4SF4 using specific antibody can be a promising therapeutics against TM4SF4-overexpressing lung adenocarcinoma. PMID:25344917

  12. [Peripheral lung adenocarcinoma versus squamous cell carcinoma: evaluation with first-pass perfusion imaging using 64-detector row CT].

    PubMed

    Li, Yuan; Yang, Zhigang; Chen, Tianwu; Yu, Jianqun; Deng, Yuping; Li, Zhenlin

    2009-04-01

    The aim of this study was to elucidate the characteristics of time attenuation curve and CT perfusion parameters for pulmonary adenocarcinomas and squamous cell carcinomas. 58 cases of pulmonary adenocarcinomas and 27 cases of squamous cell carcinomas underwent first pass CT perfusion imaging with 64-row MDCT. Data were analyzed using commercial software to generate time attenuation curve (TAC) and CT perfusion parameters, including perfusion, peak enhanced (PE), time to peak (TTP), and blood volume (BV). For TAC, there were 36.2% of type I and 63.8% of type II in adenocarcinomas, while there were 22.2% of type I and 77.8% of type II in squamous cell carcinomas. There was not significant difference (P>0.05). Perfusion, PE, TTP and BV of adenocarcinomas were 63.2 +/- 45.4 ml x min(-1) x ml(-1), 60.2 +/- 46.6 Hu, 34.8 +/- 10.2 s and 34.3 +/- 23.6 ml x 100 g(-1), respectively, while 54.3 +/- 50.2 ml x min(-1) x ml(-1), 48.5 +/- 34.9 Hu, 36.1 +/- 11.2 s and 27.6 +/- 21.7 ml x 100 g(-1), for squamous cell carcinoma, respectively. No significant differences were found between groups (P>0.05). No significant differences in TAC and CT perfusion parameters were found between adenocarcinomas and squamous cell carcinomas.

  13. Trial Comparing the Use of FLT PET to Standard CT to Assess Treatment Response of Neoadjuvant Docetaxel and Cisplatin in Stage IB-IIIA Resectable NSCLC

    ClinicalTrials.gov

    2015-04-30

    Recurrent Non-Small Cell Lung Carcinoma; Stage IB Non-Small Cell Lung Carcinoma; Stage IIA Non-Small Cell Lung Carcinoma; Stage IIB Non-Small Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IV Non-Small Cell Lung Cancer

  14. The PRKCI and SOX2 Oncogenes are Co-amplified and Cooperate to Activate Hedgehog Signaling in Lung Squamous Cell Carcinoma

    PubMed Central

    Justilien, Verline; Walsh, Michael P.; Ali, Syed A.; Thompson, E. Aubrey; Murray, Nicole R.; Fields, Alan P.

    2014-01-01

    SUMMARY We report that two oncogenes co-amplified on chromosome 3q26, PRKCI and SOX2, cooperate to drive a stem-like phenotype in lung squamous cell carcinoma (LSCC). PKCι phosphorylates SOX2, a master transcriptional regulator of stemness, and recruits it to the promoter of Hedgehog Acyl Transferase (HHAT), which catalyzes the rate-limiting step in Hh ligand production. PKCι-mediated SOX2 phosphorylation is required for HHAT promoter occupancy, HHAT expression, and maintenance of a stem-like phenotype. Primary LSCC tumors coordinately overexpress PKCι, SOX2, and HHAT, and require PKCι-SOX2-HHAT signaling to maintain a stem-like phenotype. Thus, PKCι and SOX2 are genetically, biochemically and functionally linked in LSCC, and together they drive tumorigenesis by establishing a cell autonomous Hh signaling axis. PMID:24525231

  15. Energy and protein intake and nutritional status in non-surgically treated patients with small cell anaplastic carcinoma of the lung.

    PubMed

    Enig, B; Winther, E; Hessov, I

    1986-01-01

    The spontaneous food intake and nutritional status was assessed in 23 patients with small cell anaplastic carcinoma of the lung before and two times during a treatment period of 6 weeks. Radiation therapy was given for 2 weeks followed by a course of chemotherapy and another 2 weeks of radiation therapy. The energy intake decreased during the treatment from 146 to 130 per cent of basal metabolic rate (p greater than 0.10). The protein intake remained unchanged (mean 0.9 g/kg body weight). There were insignificant and small losses of weight, body fat, free body mass and arm muscle circumference, and no changes were seen in serum albumin and serum transferrin. However, 6 patients suffered a weight loss of 5 per cent or more. No correlation existed between the nutritional parameters measured before treatment and the changes during treatment. Patients who suffered a loss of body weight could therefore not be singled out before the treatment.

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

    PubMed

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

    2014-05-01

    Owing to the need of lifelong immunosuppression, solid-organ transplant recipients are known to have an increased risk of posttransplant malignancies including lung cancer. Posttransplant neoplastic transformation of donor-derived cells giving rise to hematopoietic malignancies, Kaposi sarcoma, and basal cell carcinoma in nongraft tissues has been reported. The goal of this study was to assess the cell origin (donor versus recipient derived) of posttransplant non-small cell lung carcinomas (NSCLCs) in kidney and heart transplant recipients. An institutional database search identified 2557 kidney and heart transplant recipients in 8 consecutive years. Among this cohort, 20 (0.8%) renal and 18 (0.7%) heart transplant recipients developed NSCLC. The study cohort comprised 6 of 38 NSCLCs arising in donor-recipient sex-mismatched transplant patients. The tumor cell origin was evaluated by chromogenic in situ hybridization with Y-chromosome probe on formalin-fixed, paraffin-embedded tissues. Y-chromosome was identified in 97% ± 1% (range from 92% to 99%) of all types of nucleated cells in male control tissues. In all 5 NSCLCs from male recipients of female donor organ, Y-chromosome was identified in 97% ± 2% (range from 92% to 100%) of tumor cells, statistically equivalent to normal control (P < .001). No Y-chromosome was identified in NSCLC cells from a female recipient of male kidney. These findings suggest a recipient derivation of NSCLC arising in kidney and heart transplant recipients. A combination of histologic evaluation and chromogenic in situ hybridization with Y-chromosome analysis allows reliable determination of tissue origin in sex-mismatched solid-organ transplant recipients and may aid in management of posttransplant malignancy in such cases.

  17. Does immunohistochemistry affect response to therapy and survival of inoperable non-small cell lung carcinoma patients? A survey of 145 stage III-IV consecutive cases.

    PubMed

    Pelosi, Giuseppe; Haspinger, Eva Regina; Bimbatti, Manuela; Leone, Giorgia; Paolini, Biagio; Fabbri, Alessandra; Tamborini, Elena; Perrone, Federica; Testi, Adele; Garassino, Marina; Maisonneuve, Patrick; de Braud, Filippo; Pilotti, Silvana; Pastorino, Ugo

    2014-04-01

    Whether non-small cell lung carcinoma (NSCLC) unveiled by immunohistochemistry (IHC) has the same clinical outcome as those typed by morphology is still matter of debate. A total of 145 stage III-IV, consecutive inoperable NSCLC patients treated by chemotherapy (133 cases) or EGFR tyrosine kinase inhibitor (12 cases) and including 100 biopsies, 11 surgical specimens, and 34 cytological samples had originally accounted for 120 adenocarcinomas (ADs), 19 squamous cell carcinomas (SQCs), and 6 adenosquamous carcinomas (ADSQCs) by integrating morphology and thyroid transcription factor-1 (TTF1)/p40 IHC. Thirty-two NSCLC-not otherwise specified (NSCLC-NOS) cases were identified by morphology revision of the original diagnoses, which showed solid growth pattern (P < .001), 22 ADs, 5 SQCs, and 5 ADSQCs by IHC profiling (P < .001), and 10 gene-altered tumors (3 EGFR, 5 KRAS, and 2 ALK). While no significant relationships were observed between response to therapy and original, morphology or IHC diagnoses, driver mutations and tumor differentiation by TTF1 expression, AD run better progression-free survival (PFS) or overall survival (OS) than other tumor types by morphology (P = .010 and P = .047) and IHC (P = .033 and P = .046), respectively. Furthermore, patients with NSCLC-NOS confirmed as AD by IHC tended to have poorer OS (P = .179) and PFS (P = .193) similar to that of ADSQC and SQC (P = .702 and P = .540, respectively). A category of less differentiated AD with poorer prognosis on therapy could be identified by IHC, while there were no differences for SQC or ADSQC. The terminology of "NSCLC-NOS, favor by IHC" is appropriate to alert clinicians toward more aggressive tumors. PMID:24326823

  18. Reference standard and statistical model for intersite and temporal comparisons of CT attenuation in a multicenter quantitative lung study

    PubMed Central

    Sieren, J. P.; Newell, J. D.; Judy, P. F.; Lynch, D. A.; Chan, K. S.; Guo, J.; Hoffman, E. A.

    2012-01-01

    Purpose: The purpose of this study was to detect and analyze anomalies between a large number of computed tomography (CT) scanners, tracked over time, utilized to collect human pulmonary CT data for a national multicenter study: chronic obstructive pulmonary disease genetic epidemiology study (COPDGene). Methods: A custom designed CT reference standard “Test Object” has been developed to evaluate the relevant differences in CT attenuation between CT scanners in COPDGene. The materials used in the Test Object to assess CT scanner accuracy and precision included lung equivalent foam (−856 HU), internal air (−1000 HU), water (0 HU), and acrylic (120 HU). Nineteen examples of the Test Object were manufactured. Initially, all Test Objects were scanned on the same CT scanner before the Test Objects were sent to the 20 specific sites and 42 individual CT scanners that were used in the study. The Test Objects were scanned over 17 months while the COPDGene study continued to recruit subjects. A mixed linear effect statistical analysis of the CT scans on the 19 Test Objects was performed. The statistical model reflected influence of reconstruction kernels, tube current, individual Test Objects, CT scanner models, and temporal consistency on CT attenuation. Results: Depending on the Test Object material, there were significant differences between reconstruction kernels, tube current, individual Test Objects, CT scanner models, and temporal consistency. The two Test Object materials of most interest were lung equivalent foam and internal air. With lung equivalent foam, there were significant (p < 0.05) differences between the Siemens B31 (−856.6, ±0.82; mean ± SE) and the GE Standard (−856.6 ± 0.83) reconstruction kernel relative to the Siemens B35 reference standard (−852.5 ± 1.4). Comparing lung equivalent foam attenuation there were also significant differences between CT scanner models (p < 0.01), tube current (p < 0.005), and in temporal consistency (p

  19. Erlotinib Hydrochloride With or Without Carboplatin and Paclitaxel in Treating Patients With Stage III-IV Non-small Cell Lung Cancer

    ClinicalTrials.gov

    2016-10-19

    Adenosquamous Lung Carcinoma; Bronchioloalveolar Carcinoma; Lung Adenocarcinoma; Malignant Pericardial Effusion; Malignant Pleural Effusion; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Non-Small Cell Lung Cancer

  20. Cancer stem cells are underestimated by standard experimental methods in clear cell renal cell carcinoma

    PubMed Central

    Gedye, Craig; Sirskyj, Danylo; Lobo, Nazleen C.; Meens, Jalna; Hyatt, Elzbieta; Robinette, Michael; Fleshner, Neil; Hamilton, Robert J; Kulkarni, Girish; Zlotta, Alexandre; Evans, Andrew; Finelli, Antonio; Jewett, Michael A. S.; Ailles, Laurie E.

    2016-01-01

    Rare cancer stem cells (CSC) are proposed to be responsible for tumour propagation and re-initiation and are functionally defined by identifying tumour-initiating cells (TICs) using the xenotransplantation limiting dilution assay (LDA). While TICs in clear cell renal cell carcinoma (ccRCC) appeared rare in NOD/SCID/IL2Rγ−/− (NSG) mice, xenografts formed more efficiently from small tumour fragments, indicating the LDA underestimated ccRCC TIC frequency. Mechanistic interrogation of the LDA identified multiple steps that influence ccRCC TIC quantitation. For example, tissue disaggregation destroys most ccRCC cells, common assays significantly overestimate tumour cell viability, and microenvironmental supplementation with human extracellular factors or pharmacological inhibition of anoikis increase clonogenicity and tumourigenicity of ccRCC cell lines and primary tumour cells. Identification of these previously uncharacterized concerns that cumulatively lead to substantial underestimation of TICs in ccRCC provides a framework for development of more accurate TIC assays in the future, both for this disease and for other cancers. PMID:27121191

  1. Artificial cytokine storm combined with hyperthermia induces significant anti-tumor effect in mice inoculated with lewis lung carcinoma and B16 melanoma cells.

    PubMed

    Kushida, Shigeki; Ohmae, Hiroshi; Kamma, Hiroshi; Totsuka, Rumiko; Matsumura, Masayuki; Takeuchi, Akira; Saiki, Ikuo; Yanagawa, Toru; Onizawa, Kojiro; Ishii, Tetsuro; Ohn, Tadao

    2006-12-01

    In cancer immunotherapies combined with hyperthermia, one or two cytokines have been tested to augment the anti-tumor effect. However, the therapies have not shown sufficient improvement. The aim of this study is to find a new potent tumor immunotherapy in order to augment antitumor effect of hyperthermia by the cytokine cocktails in vivo. We used a combination therapy of local hyperthermia (LH) and various cytokine cocktails composed of IFNs (IFN-alpha, -beta, and -gamma), Thl cytokines (IL-2, -12, -15, and -18), a Th2 cytokine (IL-4), inflammatory cytokines (IL-lalpha and TNF-alpha), and dendritic cell-inducible cytokines (IL-3 and GM-CSF). These cytokines in a proper combination augmented the anti-tumor effect of LH and prolonged survival time in Lewis lung carcinoma or B16 melanoma significantly. Moreover, the 12-cytokine cocktail suppressed B 16 metastasis to the lung and lymph nodes, and complete regression of the tumors without regrowth occurred in 3 of 5 mice. In the cured three B16 mice, there was hyperplasia of lymphatic organs with many CD3-positive T lymphocytes. The most effective cytokine combination should be able to augment the anti-tumor effect of other therapies besides hyperthermia that induce the necrosis of tumor cells.

  2. Morphological changes and nuclear translocation of DLC1 tumor suppressor protein precede apoptosis in human non-small cell lung carcinoma cells

    SciTech Connect

    Yuan Baozhu Jefferson, Amy M.; Millecchia, Lyndell; Popescu, Nicholas C.; Reynolds, Steven H.

    2007-11-01

    We have previously shown that reactivation of DLC1, a RhoGAP containing tumor suppressor gene, inhibits tumorigenicity of human non-small cell lung carcinoma cells (NSCLC). After transfection of NSCLC cells with wild type (WT) DLC1, changes in cell morphology were observed. To determine whether such changes have functional implications, we generated several DLC1 mutants and examined their effects on cell morphology, proliferation, migration and apoptosis in a DLC1 deficient NSCLC cell line. We show that WT DLC1 caused actin cytoskeleton-based morphological alterations manifested as cytoplasmic extensions and membrane blebbings in most cells. Subsequently, a fraction of cells exhibiting DLC1 protein nuclear translocation (PNT) underwent caspase 3-dependent apoptosis. We also show that the RhoGAP domain is essential for the occurrence of morphological alterations, PNT and apoptosis, and the inhibition of cell migration. DLC1 PNT is dependent on a bipartite nuclear localizing sequence and most likely is regulated by a serine-rich domain at N-terminal part of the DLC1 protein. Also, we found that DLC1 functions in the cytoplasm as an inhibitor of tumor cell proliferation and migration, but in the nucleus as an inducer of apoptosis. Our analyses provide evidence for a possible link between morphological alterations, PNT and proapoptotic and anti-oncogenic activities of DLC1 in lung cancer.

  3. Effect of mopidamol on survival in carcinoma of the lung and colon: final report of Veterans Administration Cooperative Study No. 188.

    PubMed

    Zacharski, L R; Moritz, T E; Baczek, L A; Rickles, F R; Edwards, R L; Forman, W B; Forcier, R J; Cornell, C J; Haakenson, C M; Ballard, H S

    1988-03-16

    Mopidamol (RA-233), a derivative of dipyridamole, is a phosphodiesterase inhibitor that has been shown previously to limit progression of malignancy in certain experimental animal models and in a pilot study in humans. RA-233 plus chemotherapy was compared with chemotherapy alone in a 5-year double-blind trial involving 719 patients with advanced carcinomas of the lung and of the colon. RA-233 treatment was associated with a statistically significant prolongation of survival in patients with non-small cell lung cancer (N-SCLC) limited to one hemithorax and with reduction in mean plasma fibrogen concentration. RA-233 was not toxic. The favorable effects on survival could not be explained by any factor other than the RA-233 treatment. In other tumor categories tested, no differences in survival were observed. These results suggest that RA-233 is useful in the treatment of N-SCLC of limited extent. They also suggest that therapeutic intervention aimed at modified intracellular pathways might constitute a novel investigative approach to the treatment of cancer.

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

    NASA Astrophysics Data System (ADS)

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

    2016-08-01

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

  5. Morphological changes and nuclear translocation of DLC1 tumor suppressor protein precede apoptosis in human non-small cell lung carcinoma cells.

    PubMed

    Yuan, Bao-Zhu; Jefferson, Amy M; Millecchia, Lyndell; Popescu, Nicholas C; Reynolds, Steven H

    2007-11-01

    We have previously shown that reactivation of DLC1, a RhoGAP containing tumor suppressor gene, inhibits tumorigenicity of human non-small cell lung carcinoma cells (NSCLC). After transfection of NSCLC cells with wild type (WT) DLC1, changes in cell morphology were observed. To determine whether such changes have functional implications, we generated several DLC1 mutants and examined their effects on cell morphology, proliferation, migration and apoptosis in a DLC1 deficient NSCLC cell line. We show that WT DLC1 caused actin cytoskeleton-based morphological alterations manifested as cytoplasmic extensions and membrane blebbings in most cells. Subsequently, a fraction of cells exhibiting DLC1 protein nuclear translocation (PNT) underwent caspase 3-dependent apoptosis. We also show that the RhoGAP domain is essential for the occurrence of morphological alterations, PNT and apoptosis, and the inhibition of cell migration. DLC1 PNT is dependent on a bipartite nuclear localizing sequence and most likely is regulated by a serine-rich domain at N-terminal part of the DLC1 protein. Also, we found that DLC1 functions in the cytoplasm as an inhibitor of tumor cell proliferation and migration, but in the nucleus as an inducer of apoptosis. Our analyses provide evidence for a possible link between morphological alterations, PNT and proapoptotic and anti-oncogenic activities of DLC1 in lung cancer. PMID:17888903

  6. Augmentation of antimetastatic effect on Lewis lung carcinoma (3LL) in C57BL/6 mice by priming with Lactobacillus casei.

    PubMed

    Matsuzaki, T; Shimizu, Y; Yokokura, T

    1990-01-01

    The augmentation of the antimetastatic effect of heat-killed cells of Lactobacillus casei YIT9018 (LC9018) on Lewis lung carcinoma (3LL) in C57BL/6 mice by presensitization (priming) with LC9018 was examined. Intralesional injection of LC9018 into 3LL-bearing mice inhibited both the growth of the primary tumors and the formation of lung metastases, and this effect was significantly augmented by subcutaneous injection of LC9018 before the tumor inoculation. In the LC9018-primed mice, intraperitoneal administration of LC9018 into syngeneic hosts after priming induced a high level of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) in the peritoneal cavity. At this time, T cells of the spleen cells from the LC9018-primed mice proliferated and produced IL-2 when co-cultured with LC9018 as antigen in vitro. Also, the phenotype of these T cells was found to be L3T4+ and Ly-2.2- T cells by analysis by flow cytometry. These results suggest that LC9018-reactive helper T (Th) cells were induced by the priming and subsequent challenge with LC9018, and that IL-2 or IFN-gamma, which was produced by the activated LC9018-reactive Th cells, augmented a host immune response resulting the antitumor activity.

  7. An Autopsy Case of Two Distinct, Acquired Drug Resistance Mechanisms in Epidermal Growth Factor Receptor-mutant Lung Adenocarcinoma: Small Cell Carcinoma Transformation and Epidermal Growth Factor Receptor T790M Mutation.

    PubMed

    Furugen, Makoto; Uechi, Kayoko; Hirai, Jun; Aoyama, Hajime; Saio, Masanao; Yoshimi, Naoki; Kinjo, Takeshi; Miyagi, Kazuya; Haranaga, Shusaku; Higa, Futoshi; Tateyama, Masao; Fujita, Jiro

    2015-01-01

    We herein describe the case of a 63-year-old man who died from relapsed epidermal growth factor receptor gene (EGFR) exon 19 deletion lung adenocarcinoma treated with erlotinib. According to the autopsy results, he was confirmed to have small cell carcinoma without the EGFR T790M mutation in his pancreas and left kidney metastatic specimens, while the adenocarcinoma metastatic lesion in his right kidney had the EGFR T790M mutation; both retained the somatic EGFR exon 19 deletion. We herein report an autopsy case of resistance to an EGFR tyrosine kinase inhibitor via small cell carcinoma transformation and the EGFRT790M mutation in separate metastatic organs. PMID:26424310

  8. Induction of cytochrome P-450 1A1 in human hepatoma HepG2 and lung carcinoma NCI-H322 cells by motorcycle exhaust particulate.

    PubMed

    Ueng, T H; Hu, S H; Chen, R M; Wang, H W; Kuo, M L

    2000-05-26

    The effects of motorcycle exhaust particulate (MEP) on human cytochrome P-450 (P-450)-dependent monooxygenases were determined using human hepatoma cell line HepG2 and lung carcinoma cell line NCI-H322 treated with organic extracts of MEP from a two-stroke engine. Gas chromatography and mass spectrometry analysis of MEP extract revealed the presence of carcinogens benzo[a]pyrene, benz[a]anthracene, benzo[b]fluoranthene, benzo[k]fluoranthene, benzo[g,h,i]perylene, chrysene, and indeno[1,2,3-c,d]pyrene in the chemical mixture. Treatment with MEP extract produced concentration- and time-dependent increases of monooxygenase activity in HepG2 cells. Treatment of the cells with 100 microg/ ml MEP extract for 24 h markedly increased benzo[a]pyrene hydroxylation, 7-ethoxycoumarin, and 7-ethoxyresorufin O-deethylation activities in microsomes. Immunoblot analysis of microsomal proteins using mouse monoclonal antibody 1-12-3 against P-450 1A1 revealed that MEP extract induced a P-450-immunorelated protein in the hepatoma cells. RNA blot analysis of cellular total RNA using a human P-450 1A1 3'-end cDNA probe showed that MEP extract increased the level of a hybridizable P-450 mRNA. These P-450 1A1 inductive effects of MEP extract were similar to those from treatment with 10 microM benzo[a]pyrene or 3-methylcholanthrene (3-MC) in HepG2 cells. Treatment of lung carcinoma NCI-H322 cells with 100 microg/ml MEP extract, 10 microM benzo[a]pyrene, or 3-MC resulted in induction of monooxygenase activity, protein, and mRNA of P-450 1A1, similar to the induction observed with the hepatoma cells. The present study demonstrates that MEP extract has the ability to induce human hepatic and pulmonary P-450 1A1 in the liver- and lung-derived cell lines, and the induction involves a pretranslational mechanism. Induction of the human hepatic and pulmonary P-450 1A1 in vitro may provide important information in the assessment of MEP metabolism and toxicity in humans.

  9. Association of Nuclear PIM1 Expression with Lymph Node Metastasis and Poor Prognosis in Patients with Lung Adenocarcinoma and Squamous Cell Carcinoma

    PubMed Central

    Jiang, Richeng; Wang, Xinyue; Jin, Ziliang; Li, Kai

    2016-01-01

    Increasing evidence indicates that aberrant expression of PIM1, p-STAT3 and c-MYC is involved in the pathogenesis of various solid tumors, but its prognostic value is still unclear in non-small cell lung cancer (NSCLC). Here, we sought to evaluate the expression and prognostic role of these markers in patients with lung adenocarcinoma (AD) and squamous cell carcinoma (SCC). Real time RT-PCR and Western blotting was used to analyze the mRNA and protein expression of PIM1 in NSCLC cell lines, respectively. The expression of PIM1, p-STAT3, and c-MYC was immunohistochemically tested in archival tumor samples from 194 lung AD and SCC patients. High nuclear PIM1 expression was detected in 43.3% of ADs and SCCs, and was significantly correlated with lymph node (LN) metastasis (P = 0.028) and histology (P = 0.003). High nuclear PIM1 expression (P = 0.034), locally advanced stage (P < 0.001), AD (P = 0.007) and poor pathologic differentiation (P = 0.002) were correlated with worse disease-free survival (DFS). High nuclear PIM1 expression (P = 0.009), advanced clinical stage (P < 0.001) and poor pathologic differentiation (P = 0.004) were independent unfavorable prognostic factors for overall survival (OS). High p-STAT3 expression was not associated with OS but significantly correlated with LN metastasis, while c-MYC was not significantly correlated with any clinicopathological parameter or survival. Therefore, in AD and SCC patients, nuclear PIM1 expression level is an independent factor for DFS and OS and it might serve as a predictive biomarker for outcome. PMID:26918046

  10. The clinicopathological significance and ethnic difference of FHIT hypermethylation in non-small-cell lung carcinoma: a meta-analysis and literature review.

    PubMed

    Wu, Xiaoyu; Wu, Guannan; Yao, Xuequan; Hou, Gang; Jiang, Feng

    2016-01-01

    Emerging evidence indicates that FHIT is a candidate tumor suppressor in many types of tumors including non-small-cell lung carcinoma (NSCLC). However, the prognostic value and correlation between FHIT hypermethylation and clinicopathological characteristics of NSCLC remains unclear. In this report, we performed a meta-analysis to evaluate the effects of FHIT hypermethylation on the incidence of NSCLC and clinicopathological characteristics of human NSCLC patients. Final analysis of 1,801 NSCLC patients from 18 eligible studies was performed. FHIT hypermethylation was found to be significantly higher in NSCLC than in normal lung tissue. The pooled odds ratio (OR) from ten studies included 819 NSCLC and 792 normal lung tissues (OR =7.51, 95% confidence interval [CI] =2.98-18.91, P<0.0001). Subgroup analysis based on ethnicity implied that FHIT hypermethylation level was higher in NSCLC tissues than in normal tissues in both Caucasians (P=0.02) and Asians (P<0.0001), indicating that the difference in Asians was much more significant. FHIT hypermethylation was also correlated with sex status, smoking status, as well as pathological types. In addition, patients with FHIT hypermethylation had a lower survival rate than those without (hazard ratio =1.73, 95% CI =1.10-2.71, P=0.02). The results of this meta-analysis suggest that FHIT hypermethylation is associated with an increased risk and poor survival in NSCLC patients. FHIT hypermethylation, which induces the inactivation of FHIT gene, plays an important role in the carcinogenesis and clinical outcome and may serve as a potential diagnostic marker and drug target of NSCLC.

  11. Human Noxin is an anti-apoptotic protein in response to DNA damage of A549 non-small cell lung carcinoma.

    PubMed

    Won, Kyoung-Jae; Im, Joo-Young; Yun, Chae-Ok; Chung, Kyung-Sook; Kim, Young Joo; Lee, Jung-Sun; Jung, Young-Jin; Kim, Bo-Kyung; Song, Kyung Bin; Kim, Young-Ho; Chun, Ho-Kyung; Jung, Kyeong Eun; Kim, Moon-Hee; Won, Misun

    2014-06-01

    Human Noxin (hNoxin, C11Orf82), a homolog of mouse noxin, is highly expressed in colorectal and lung cancer tissues. hNoxin contains a DNA-binding C-domain in RPA1, which mediates DNA metabolic processes, such as DNA replication and DNA repair. Expression of hNoxin is associated with S phase in cancer cells and in normal cells. Expression of hNoxin was induced by ultraviolet (UV) irradiation. Knockdown of hNoxin caused growth inhibition of colorectal and lung cancer cells. The comet assay and western blot analysis revealed that hNoxin knockdown induced apoptosis through activation of p38 mitogen-activated protein kinase (MAPK)/p53 in non-small cell lung carcinoma A549 cells. Furthermore, simultaneous hNoxin knockdown and treatment with DNA-damaging agents, such as camptothecin (CPT) and UV irradiation, enhanced apoptosis, whereas Trichostatin A (TSA) did not. However, transient overexpression of hNoxin rescued cells from DNA damage-induced apoptosis but did not block apoptosis in the absence of DNA damage. These results suggest that hNoxin may be associated with inhibition of apoptosis in response to DNA damage. An adenovirus expressing a short hairpin RNA against hNoxin transcripts significantly suppressed the growth of A549 tumor xenografts, indicating that hNoxin knockdown has in vivo anti-tumor efficacy. Thus, hNoxin is a DNA damage-induced anti-apoptotic protein and potential therapeutic target in cancer.

  12. Leptospermum flavescens Constituent-LF1 Causes Cell Death through the Induction of Cell Cycle Arrest and Apoptosis in Human Lung Carcinoma Cells

    PubMed Central

    Navanesan, Suerialoasan; Abdul Wahab, Norhanom; Manickam, Sugumaran; Sim, Kae Shin

    2015-01-01

    Leptospermum flavescens Sm. (Myrtaceae), locally known as ‘Senna makki’ is a smallish tree that is widespread and recorded to naturally occur in the montane regions above 900 m a.s.l from Burma to Australia. Although the species is recorded to be used traditionally to treat various ailments, there is limited data on biological and chemical investigations of L. flavescens. The aim of the present study was to investigate and understand the ability of L. flavescens in inducing cell death in lung cancer cells. The cytotoxic potentials of the extraction yields (methanol, hexane, ethyl acetate and water extracts as wells as a semi pure fraction, LF1) were evaluated against two human non-small cell lung carcinoma cell lines (A549 and NCI-H1299) using the MTT assay. LF1 showed the greatest cytotoxic effect against both cell lines with IC50 values of 7.12 ± 0.07 and 9.62 ± 0.50 μg/ml respectively. LF1 treated cells showed a sub-G1 region in the cell cycle analysis and also caused the presence of apoptotic morphologies in cells stained with acridine orange and ethidium bromide. Treatment with LF1 manifested an apoptotic population in cells that were evaluated using the Annexin V/ propidium iodide assay. Increasing dosage of LF1 caused a rise in the presence of activated caspase-3 enzymes in treated cells. Blockage of cell cycle progression was also observed in LF1-treated cells. These findings suggest that LF1 induces apoptosis and cell cycle arrest in treated lung cancer cells. Further studies are being conducted to isolate and identify the active compound as well to better understand the mechanism involved in inducing cell death. PMID:26287817

  13. Use of reverse phase protein microarrays and reference standard development for molecular network analysis of metastatic ovarian carcinoma.

    PubMed

    Sheehan, Katherine M; Calvert, Valerie S; Kay, Elaine W; Lu, Yiling; Fishman, David; Espina, Virginia; Aquino, Joy; Speer, Runa; Araujo, Robyn; Mills, Gordon B; Liotta, Lance A; Petricoin, Emanuel F; Wulfkuhle, Julia D

    2005-04-01

    Cancer can be defined as a deregulation or hyperactivity in the ongoing network of intracellular and extracellular signaling events. Reverse phase protein microarray technology may offer a new opportunity to measure and profile these signaling pathways, providing data on post-translational phosphorylation events not obtainable by gene microarray analysis. Treatment of ovarian epithelial carcinoma almost always takes place in a metastatic setting since unfortunately the disease is often not detected until later stages. Thus, in addition to elucidation of the molecular network within a tumor specimen, critical questions are to what extent do signaling changes occur upon metastasis and are there common pathway elements that arise in the metastatic microenvironment. For individualized combinatorial therapy, ideal therapeutic selection based on proteomic mapping of phosphorylation end points may require evaluation of the patient's metastatic tissue. Extending these findings to the bedside will require the development of optimized protocols and reference standards. We have developed a reference standard based on a mixture of phosphorylated peptides to begin to address this challenge.

  14. Correlation of dosimetric parameters obtained with the analytical anisotropic algorithm and toxicity of chest chemoradiation in lung carcinoma

    SciTech Connect

    Cartier, Lysian; Auberdiac, Pierre; Khodri, Mustapha; Malkoun, Nadia; Chargari, Cyrus; Thorin, Julie; Melis, Adrien; Talabard, Jean-Noeel; Laroche, Guy de; Fournel, Pierre; Tiffet, Olivier; Schmitt, Thierry; and others

    2012-07-01

    The purpose of this study was to analyze and revisit toxicity related to chest chemoradiotherapy and to correlate these side effects with dosimetric parameters obtained using analytical anisotropic algorithm (AAA) in locally unresectable advanced lung cancer. We retrospectively analyzed data from 47 lung cancer patients between 2005 and 2008. All received conformal 3D radiotherapy using high-energy linear accelerator plus concomitant chemotherapy. All treatment planning data were transferred into Eclipse 8.05 (Varian Medical Systems, Palo Alto, CA) and dosimetric calculations were performed using AAA. Thirty-three patients (70.2%) developed acute pneumopathy after radiotherapy (grades 1 and 2). One patient (2.1%) presented with grade 3 pneumopathy. Thirty-one (66%) presented with grades 1-2 lung fibrosis, and 1 patient presented with grade 3 lung fibrosis. Thirty-four patients (72.3%) developed grade 1-2 acute oesophagic toxicity. Four patients (8.5%) presented with grades 3 and 4 dysphagia, necessitating prolonged parenteral nutrition. Median prescribed dose was 64 Gy (range 50-74) with conventional fractionation (2 Gy per fraction). Dose-volume constraints were respected with a median V20 of 23.5% (maximum 34%) and a median V30 of 17% (maximum 25%). The median dose delivered to healthy contralateral lung was 13.1 Gy (maximum 18.1 Gy). At univariate analysis, larger planning target volume and V20 were significantly associated with the probability of grade {>=}2 radiation-induced pneumopathy (p = 0.022 and p = 0.017, respectively). No relation between oesophagic toxicity and clinical/dosimetric parameters could be established. Using AAA, the present results confirm the predictive value of the V20 for lung toxicity as already demonstrated with the conventional pencil beam convolution approach.

  15. Drug-induced myocarditis after nivolumab treatment in a patient with PDL1- negative squamous cell carcinoma of the lung.

    PubMed

    Semper, H; Muehlberg, F; Schulz-Menger, J; Allewelt, M; Grohé, C

    2016-09-01

    Immunotherapy such as nivolumab is a new promising therapeutic option for advanced stage non small cell lung cancer (NSCLC). Due to the interference with the immune system previously unknown side effects are observed both in clinical studies and experience. Autoimmune phenomena effecting skin, gastrointestinal tract, endocrine glands, kidney and lung have been described. Up to now there is only limited information regarding potential cardiac side effects. We present a case of symptomatic drug induced myocarditis after nine cycles of nivolumab in a patient with efficient anticancer response. PMID:27565924

  16. Specific route mapping visualized with GFP of single-file streaming contralateral and systemic metastasis of Lewis lung carcinoma cells beginning within hours of orthotopic implantation [correction of implantion].

    PubMed

    Rashidi, Babak; Moossa, Abdool R; Hoffman, Robert M

    2013-08-01

    In this study, we visualized the origin of Lewis lung carcinoma metastasis after transducing tumor cells with green fluorescent protein (GFP) and transplanting them orthotopically in the middle lobe of the right lung of nude mice. Metastasis was visualized in live tissue at single cell resolution by GFP-expression as early as 18 h post-tumor transplant. At this time, single-file streaming lung carcinoma cells already had invaded inferiorly via a tubular lymphatic structure crossing the lower lobes of the lung to the ipsilateral diaphragmatic surface. By post-implantation day 2, the ipsilateral lower lobes of the lung were involved with metastatic cells. By post-implantation day 3, the ipsilateral lower lobes of the lung and the ipsilateral diaphragmatic surface were highly involved with streaming metastatic cells trafficking in single file. By day 4 post-implantation, cancer cells invaded across the diaphragm to the contralateral diaphragmatic surface. Metastatic cells then invaded superiorly through a lymphatic vessel to involve the contralateral mediastinal lymph nodes. In this model of lung cancer, the origin of metastasis was an inferior invasion from the implanted tumor via a lymphatic duct to the ipsilateral diaphragmatic surface. The cancer cells from this site invaded on the surface of the diaphragm to the contralateral diaphragmatic surface and proceeded superiorly through a lymphatic duct to contralateral lymph nodes. Other organs such as the kidneys and the adrenal glands later became involved with metastasis with the contralateral mediastinal lymph nodes as the source. The use of GFP and the highly metastatic orthotopic lung cancer model allowed the visualization of the origin of metastasis at the single-cell level and demonstrated the critical role of lymphatic ducts and the diaphragmatic surface as the path to the contralateral side.

  17. Detection of the EGFR mutation in exhaled breath condensate from a heavy smoker with squamous cell carcinoma of the lung.

    PubMed

    Zhang, Dan; Takigawa, Nagio; Ochi, Nobuaki; Tanimoto, Yasushi; Noujima, Daisuke; Chen, Yan Yan; Tanimoto, Mitsune; Kiura, Katsuyuki

    2011-09-01

    A 61-year-old male smoker (40 pack-years) presented with right chest pain. Computed tomography of the chest revealed a cavitary mass in the right lower lobe. A transbronchial biopsy showed squamous cell carcinoma. We examined epidermal growth factor receptor (EGFR) mutations in exhaled breath condensate (EBC). The DNA extracted from his EBC showed a deletion mutation in exon 19. Subsequently, the del E746-A750 mutation in exon 19 in a transbronchial tissue specimen was confirmed. Although he underwent whole-brain irradiation against multiple brain metastases, he had paralysis of the left side of the body and his performance status was 3. The patient was treated with gefitinib. He had marked tumor regression and no symptoms. Although only a small percentage of heavy smokers with squamous cell carcinoma harbor EGFR mutations, they probably benefit from EGFR-tyrosine kinase inhibitors. EGFR mutation status in the patients having such clinical features might be examined. PMID:21684624

  18. A novel germline mutation in a patient with nevoid basal cell carcinoma syndrome showing cystic lesion in the lung.

    PubMed

    Miyata, Ryo; Kurosawa, Manabu; Sato, Masaaki; Kono, Tomoya; Takubo, Yasutaka; Okai, Shinsaku; Yamada, Keisuke; Shinkura, Reiko; Date, Hiroshi; Matsuda, Fumihiko

    2015-01-01

    Nevoid basal cell carcinoma syndrome (NBCCS) manifests multiple defects involving the skin, endocrine and nervous systems, eyes and bones. Mutations in the patched homologue 1 (PTCH1) gene are the underlying causes of NBCCS, leading to aberrant cell proliferation through constitutive activation of the hedgehog signaling pathway. We identified a novel frameshift mutation (c.1207dupT) of PTCH1 in a NBCCS patient, which might explain multiple cystic lesions and neoplastic growth in the patient. PMID:27081528

  19. Antioxidant Activity and Cytotoxicity Effect of Cocoa Beans Subjected to Different Processing Conditions in Human Lung Carcinoma Cells

    PubMed Central

    Bauer, Deborah; de Abreu, Joel Pimentel; Oliveira, Hilana Salete Silva; Goes-Neto, Aristoteles; Koblitz, Maria Gabriela Bello

    2016-01-01

    Lung cancer is a common malignancy in men and the second leading cause of cancer-related mortality in men in the western world. Phenolic cocoa ingredients have a strong antioxidative activity and the potential to have a protective effect against cancer. In the present study, we have evaluated the influence of cocoa beans subjected to different processing conditions on cell viability and apoptosis of human lung cancer cells (A549). We measured the viability of lung cells treated with cocoa beans, unroasted slates (US), roasted slates (RS), unroasted well fermented (UWF) cocoa, and roasted well fermented (RWF) cocoa for 24 h. Using an MTT assay, we observed a decrease in the viability of A549 cells after treatment with cocoa bean extracts. Flow cytometer analysis revealed that cocoa beans increased the percentage of cells in sub-G1 phase and promoted up to twofold increase of apoptotic cells when compared to the control group. Taken together, the present study suggests that cocoa beans may have a protective effect against lung cancer. PMID:27034742

  20. Antioxidant Activity and Cytotoxicity Effect of Cocoa Beans Subjected to Different Processing Conditions in Human Lung Carcinoma Cells.

    PubMed

    Bauer, Deborah; de Abreu, Joel Pimentel; Oliveira, Hilana Salete Silva; Goes-Neto, Aristoteles; Koblitz, Maria Gabriela Bello; Teodoro, Anderson Junger

    2016-01-01

    Lung cancer is a common malignancy in men and the second leading cause of cancer-related mortality in men in the western world. Phenolic cocoa ingredients have a strong antioxidative activity and the potential to have a protective effect against cancer. In the present study, we have evaluated the influence of cocoa beans subjected to different processing conditions on cell viability and apoptosis of human lung cancer cells (A549). We measured the viability of lung cells treated with cocoa beans, unroasted slates (US), roasted slates (RS), unroasted well fermented (UWF) cocoa, and roasted well fermented (RWF) cocoa for 24 h. Using an MTT assay, we observed a decrease in the viability of A549 cells after treatment with cocoa bean extracts. Flow cytometer analysis revealed that cocoa beans increased the percentage of cells in sub-G1 phase and promoted up to twofold increase of apoptotic cells when compared to the control group. Taken together, the present study suggests that cocoa beans may have a protective effect against lung cancer. PMID:27034742

  1. Antioxidant Activity and Cytotoxicity Effect of Cocoa Beans Subjected to Different Processing Conditions in Human Lung Carcinoma Cells.

    PubMed

    Bauer, Deborah; de Abreu, Joel Pimentel; Oliveira, Hilana Salete Silva; Goes-Neto, Aristoteles; Koblitz, Maria Gabriela Bello; Teodoro, Anderson Junger

    2016-01-01

    Lung cancer is a common malignancy in men and the second leading cause of cancer-related mortality in men in the western world. Phenolic cocoa ingredients have a strong antioxidative activity and the potential to have a protective effect against cancer. In the present study, we have evaluated the influence of cocoa beans subjected to different processing conditions on cell viability and apoptosis of human lung cancer cells (A549). We measured the viability of lung cells treated with cocoa beans, unroasted slates (US), roasted slates (RS), unroasted well fermented (UWF) cocoa, and roasted well fermented (RWF) cocoa for 24 h. Using an MTT assay, we observed a decrease in the viability of A549 cells after treatment with cocoa bean extracts. Flow cytometer analysis revealed that cocoa beans increased the percentage of cells in sub-G1 phase and promoted up to twofold increase of apoptotic cells when compared to the control group. Taken together, the present study suggests that cocoa beans may have a protective effect against lung cancer.

  2. PET-Adjusted Intensity Modulated Radiation Therapy and Combination Chemotherapy in Treating Patients With Stage II-IV Non-small Cell Lung Cancer

    ClinicalTrials.gov

    2016-01-10

    Metastatic Malignant Neoplasm in the Brain; Recurrent Non-Small Cell Lung Carcinoma; Stage IIA Non-Small Cell Lung Carcinoma; Stage IIB Non-Small Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Non-Small Cell Lung Cancer

  3. The role of the immune system in non-small cell lung carcinoma and potential for therapeutic intervention

    PubMed Central

    2015-01-01

    Over a hundred years after the first description of this disease, lung cancer represents one of the major challenges in oncology. Radical treatment cannot be introduced in more than 70% of cases and overall survival rate does not exceed 15%. The immunosurveillance of lung cancer may be effective in early oncogenesis but is inhibited in the course of developing a clinically detectable tumor. Very low and heterogonous antigenicity of lung cancer cells leads to passive escape from anti-cancer immune defense. The cytotoxic lymphocytes (CTLs) that play a main role in the anticancer response are actively suppressed in the tumor environment and following regulatory mechanisms inhibit the recognition of tumor antigens by antigen presenting cells. The population of regulatory T cells (Tregs) is augmented and the expression of transcription factor—Foxp3 is markedly increased on tumor cells and tumor infiltrating lymphocytes (TIL). It is accomplished by M2 macrophage polarization, the activity of myeloid derived suppressor cells (MDSCs) and a significantly elevated concentration of cytokines: transforming growth factor beta (TGFβ) and IL-10 in the tumor microenvironment. Very active suppression of immune protection is the predominant role of the programmed death 1 (PD-1)-PD-L1 pathway. The blockage of this pathway was found to be an effective treatment approach; therefore the monoclonal antibodies are being intensively investigated in lung cancer patients. Cytotoxic T lymphocyte antigen-4 (CTLA-4) is the molecule capable of inhibiting the activation signal. The antibody anti-CTLA-4 improves CTLs function in solid tumors and lung cancer patients may benefit from use of this agent. The second way in lung cancer immunotherapy is production of anti-cancer vaccines using recognized cancer antigens: MAGE-A3, membrane associated glycoprotein (MUC-1), and EGF. It was recently shown in ongoing clinical trials that combined therapies: immune- and chemotherapy, radiotherapy or

  4. A lung nematode in Canadian Arctic muskoxen. Standard radiographic and computed tomographic imaging.

    PubMed

    Kutz, S J; Fisher, K; Polley, L

    1999-07-01

    Medical imaging was used before death to follow the development of U. pallikuukensis infection in muskoxen and postmortem to investigate the distribution and characteristics of parasite-associated pulmonary cysts. In two experimentally infected animals, lesions were not visible radiographically until days 178 and 191 PI, 3 months after the parasites became patent. Serial radiographs taken throughout the period of patency of one animal showed an initial increase in lesion size by day 415 PI, but by day 789 PI, lesions had stabilized or decreased in size. Although all lesions detected postmortem were not visible radiographically during life, the radiographs did provide an indication of the relative severity of infection. In contrast to other parasitic pneumonias, there was no evidence of pulmonary disease outside of the discrete parasitic cysts. Radiographs of lungs postmortem proved to be an effective tool for locating parasitic cysts in a lightly infected muskox and demonstrated a bronchovascular cyst distribution. Postmortem CT provided a more rapid and detailed assessment of the number, size, and distribution of cysts in the lungs of one muskox.

  5. A lung nematode in Canadian Arctic muskoxen. Standard radiographic and computed tomographic imaging.

    PubMed

    Kutz, S J; Fisher, K; Polley, L

    1999-07-01

    Medical imaging was used before death to follow the development of U. pallikuukensis infection in muskoxen and postmortem to investigate the distribution and characteristics of parasite-associated pulmonary cysts. In two experimentally infected animals, lesions were not visible radiographically until days 178 and 191 PI, 3 months after the parasites became patent. Serial radiographs taken throughout the period of patency of one animal showed an initial increase in lesion size by day 415 PI, but by day 789 PI, lesions had stabilized or decreased in size. Although all lesions detected postmortem were not visible radiographically during life, the radiographs did provide an indication of the relative severity of infection. In contrast to other parasitic pneumonias, there was no evidence of pulmonary disease outside of the discrete parasitic cysts. Radiographs of lungs postmortem proved to be an effective tool for locating parasitic cysts in a lightly infected muskox and demonstrated a bronchovascular cyst distribution. Postmortem CT provided a more rapid and detailed assessment of the number, size, and distribution of cysts in the lungs of one muskox. PMID:10442391

  6. Genomic Copy Number Signatures Uncovered a Genetically Distinct Group from Adenocarcinoma and Squamous Cell Carcinoma in Non-Small Cell Lung Cancer.

    PubMed

    Lee, Eunjung; Moon, Ji Wook; Wang, Xianfu; Kim, Chungyeul; Li, Shibo; Shin, Bong Kyung; Jung, Wonkyung; Kim, Hyun Koo; Kim, Han Kyeom; Lee, Ji-Yun

    2015-08-01

    Adenocarcinoma (AC) and squamous cell carcinoma (SCC) of non-small cell lung carcinoma (NSCLC) have different clinical presentations, morphologies, treatments, and prognoses. Recent studies suggested that fundamental genetic alterations related to carcinogenesis of each tumor type may be different. In this study, we investigated the genomic alterations of 47 primary NSCLC samples (22 ACs and 25 SCCs) as well as the corresponding normal tissue using array comparative genomic hybridization. Frequent copy number alterations (CNAs), which were identified in more than 68% of all of the cases, were evaluated in each subtype (SCC and AC), and a CNA signature was established. Among these CNAs, 37 genes from the SCCs and 15 genes from the ACs were located in a region of gain, and 4 genes from the SCCs and 13 genes from the ACs were located in a region of loss. The most frequent gain was located on 3q26-29 including the gene TP63 in SCCs and 7q11.23 and 7q36.3 in ACs. Moreover, we identified 3 genetically distinct groups (group I [16 SCC] with CNA signature of SCC; group II [7 SCC + 8 AC], which has a genetically distinctive CNA signature from SCC and AC; and group III [2 SCC + 14 AC] with CNA signature of AC) by gene clustering extracted from CNAs, which are associated with a prognosis. The present study contributed to the molecular characterization of AC and SCC of NSCLC and showed a subtype of tumor that has a unique genetic CNA signature. However, further study about the significance of these 3 distinct groups and their usefulness as a diagnostic marker of identified CNAs is necessary.

  7. Prospective randomized study of various irradiation doses and fractionation schedules in the treatment of inoperable non-oat-cell carcinoma of the lung

    SciTech Connect

    Perez, C.A.; Stanley, K.; Rubin, P.; Kramer, S.; Brady, L.; Perez-Tamayo, R.; Brown, G.S.; Concannon, J.; Rotman, M.; Seydel, H.G.

    1980-06-01

    Analysis is presented of a prospective randomized study involving 365 patients with histologically proven unresectable non-oat-cell carcinoma of the lung treated with deffinitive radiotherapy. The patients were radomized to one of four treatment regimens: 4000 rad split course, or 4000, 5000, or 6000-rad continuous courses in five fractions per week. Ninety to 100 patients were accessioned to each group. The one-year survival rate is 50% and the two-year survival rate, 25%. The patients treated with the split course have the lowest survival rate in comparison with the other groups. The complete and partial local regression of tumor was 49% in patients treated with 4000 rad and 55% in the groups treated with 5000 and 6000 rad. For patients who achieved complete regression of the tumor following irradiation, the two-year survival rate is 40%, in contrast to 20% for those with partial regression, and no survivors among the patients with stable or progressive disease. The incidence of intrathoracic recurrence was 33% for patients treated with 6000 rad, 39% for those receiving 5000 rad, and 44 to 49% for those treated with a 4000-rad split or continuous course. At present, the data stongly suggest that patients treated with 5000 or 6000 rad have a better response, tumor control, and survival rate than those receiving lower doses. Patients with high performance status or with tumors in earlier stages have a two-year survival rate of approx. 40%, in comparison with 20% for other patients. The various irradiation regimens have been well tolerated, with complications being slightly higher in the 4000-rad split course group and in the 6000-rad continuous course group. The most frequent complications have been pneumonitis, pulmonary fibrosis, and dyspagia due to transient esophagitis. Further investigation will be necessary before the optimal management of patients with bronchogenic carcinoma by irradiation is established.

  8. Cell membrane CD44v6 levels in squamous cell carcinoma of the lung: association with high cellular proliferation and high concentrations of EGFR and CD44v5.

    PubMed

    Ruibal, Álvaro; Aguiar, Pablo; Del Río, María Carmen; Nuñez, Matilde Isabel; Pubul, Virginia; Herranz, Michel

    2015-01-01

    Membranous CD44v6 levels in tumors and surrounding samples obtained from 94 patients with squamous cell lung carcinomas were studied and compared to clinical stage, cellular proliferation, membranous CD44v5 levels, epidermal growth factor receptor EGFR and cytoplasmatic concentrations of CYFRA 21.1. CD44v6 positive values were observed in 33/38 non-tumor samples and in 76/94 tumor samples, but there were not statistically significant differences between both subgroups. In CD44v6 positive tumor samples, CD44v6 was not associated with clinical stage, histological grade, ploidy and lymph node involvement, but significant association was found with high cellular proliferation. Likewise, CD44v6 positive tumors had significantly higher levels of EGFR and CD44v5. In patients with squamous cell lung carcinomas and clinical stage I, positive CD44v6 cases were associated with the same parameters. Furthermore, positive CD44v5 squamous tumors were associated significantly with histological grade III and lower levels of CYFRA21.1. Our findings support the value of CD44v6 as a possible indicator of poor outcome in patients with squamous lung carcinomas. PMID:25809603

  9. A critical re-assessment of DNA repair gene promoter methylation in non-small cell lung carcinoma

    PubMed Central

    Do, Hongdo; Wong, Nicholas C.; Murone, Carmel; John, Thomas; Solomon, Benjamin; Mitchell, Paul L.; Dobrovic, Alexander

    2014-01-01

    DNA repair genes that have been inactivated by promoter methylation offer potential therapeutic targets either by targeting the specific repair deficiency, or by synthetic lethal approaches. This study evaluated promoter methylation status for eight selected DNA repair genes (ATM, BRCA1, ERCC1, MGMT, MLH1, NEIL1, RAD23B and XPC) in 56 non-small cell lung cancer (NSCLC) tumours and 11 lung cell lines using the methylation-sensitive high resolution melting (MS-HRM) methodology. Frequent methylation in NEIL1 (42%) and infrequent methylation in ERCC1 (2%) and RAD23B (2%) are reported for the first time in NSCLC. MGMT methylation was detected in 13% of the NSCLCs. Contrary to previous studies, methylation was not detected in ATM, BRCA1, MLH1 and XPC. Data from The Cancer Genome Atlas (TCGA) was consistent with these findings. The study emphasises the importance of using appropriate methodology for accurate assessment of promoter methylation. PMID:24569633

  10. Lung Master Protocol (Lung-MAP)-A Biomarker-Driven Protocol for Accelerating Development of Therapies for Squamous Cell Lung Cancer: SWOG S1400.

    PubMed

    Herbst, Roy S; Gandara, David R; Hirsch, Fred R; Redman, Mary W; LeBlanc, Michael; Mack, Philip C; Schwartz, Lawrence H; Vokes, Everett; Ramalingam, Suresh S; Bradley, Jeffrey D; Sparks, Dana; Zhou, Yang; Miwa, Crystal; Miller, Vincent A; Yelensky, Roman; Li, Yali; Allen, Jeff D; Sigal, Ellen V; Wholley, David; Sigman, Caroline C; Blumenthal, Gideon M; Malik, Shakun; Kelloff, Gary J; Abrams, Jeffrey S; Blanke, Charles D; Papadimitrakopoulou, Vassiliki A

    2015-04-01

    The Lung Master Protocol (Lung-MAP, S1400) is a groundbreaking clinical trial designed to advance the efficient development of targeted therapies for squamous cell carcinoma (SCC) of the lung. There are no approved targeted therapies specific to advanced lung SCC, although The Cancer Genome Atlas project and similar studies have detected a significant number of somatic gene mutations/amplifications in lung SCC, some of which are targetable by investigational agents. However, the frequency of these changes is low (5%-20%), making recruitment and study conduct challenging in the traditional clinical trial setting. Here, we describe our approach to development of a biomarker-driven phase II/II multisubstudy "Master Protocol," using a common platform (next-generation DNA sequencing) to identify actionable molecular abnormalities, followed by randomization to the relevant targeted therapy versus standard of care.

  11. Tudor staphylococcal nuclease drives chemoresistance of non-small cell lung carcinoma cells by regulating S100A11.

    PubMed

    Zagryazhskaya, Anna; Surova, Olga; Akbar, Nadeem S; Allavena, Giulia; Gyuraszova, Katarina; Zborovskaya, Irina B; Tchevkina, Elena M; Zhivotovsky, Boris

    2015-05-20

    Lung cancer is the leading cause of cancer-related deaths worldwide. Non-small cell lung cancer (NSCLC), the major lung cancer subtype, is characterized by high resistance to chemotherapy. Here we demonstrate that Tudor staphylococcal nuclease (SND1 or TSN) is overexpressed in NSCLC cell lines and tissues, and is important for maintaining NSCLC chemoresistance. Downregulation of TSN by RNAi in NSCLC cells led to strong potentiation of cell death in response to cisplatin. Silencing of TSN was accompanied by a significant decrease in S100A11 expression at both mRNA and protein level. Downregulation of S100A11 by RNAi resulted in enhanced sensitivity of NSCLC cells to cisplatin, oxaliplatin and 5-fluouracil. AACOCF(3), a phospholipase A(2) (PLA(2)) inhibitor, strongly abrogated chemosensitization upon silencing of S100A11 suggesting that PLA(2) inhibition by S100A11 governs the chemoresistance of NSCLC. Moreover, silencing of S100A11 stimulated mitochondrial superoxide production, which was decreased by AACOCF(3), as well as N-acetyl-L-cysteine, which also mimicked the effect of PLA(2) inhibitor on NSCLC chemosensitization upon S100A11 silencing. Thus, we present the novel TSN-S100A11-PLA(2) axis regulating superoxide-dependent apoptosis, triggered by platinum-based chemotherapeutic agents in NSCLC that may be targeted by innovative cancer therapies.

  12. International Society for Heart and Lung Transplantation working formulation of a standardized nomenclature for cardiac allograft vasculopathy-2010.

    PubMed

    Mehra, Mandeep R; Crespo-Leiro, Maria G; Dipchand, Anne; Ensminger, Stephan M; Hiemann, Nicola E; Kobashigawa, Jon A; Madsen, Joren; Parameshwar, Jayan; Starling, Randall C; Uber, Patricia A

    2010-07-01

    The development of cardiac allograft vasculopathy remains the Achilles heel of cardiac transplantation. Unfortunately, the definitions of cardiac allograft vasculopathy are diverse, and there are no uniform international standards for the nomenclature of this entity. This consensus document, commissioned by the International Society of Heart and Lung Transplantation Board, is based on best evidence and clinical consensus derived from critical analysis of available information pertaining to angiography, intravascular ultrasound imaging, microvascular function, cardiac allograft histology, circulating immune markers, non-invasive imaging tests, and gene-based and protein-based biomarkers. This document represents a working formulation for an international nomenclature of cardiac allograft vasculopathy, similar to the development of the system for adjudication of cardiac allograft rejection by histology.

  13. International Society for Heart and Lung Transplantation working formulation of a standardized nomenclature for cardiac allograft vasculopathy-2010.

    PubMed

    Mehra, Mandeep R; Crespo-Leiro, Maria G; Dipchand, Anne; Ensminger, Stephan M; Hiemann, Nicola E; Kobashigawa, Jon A; Madsen, Joren; Parameshwar, Jayan; Starling, Randall C; Uber, Patricia A

    2010-07-01

    The development of cardiac allograft vasculopathy remains the Achilles heel of cardiac transplantation. Unfortunately, the definitions of cardiac allograft vasculopathy are diverse, and there are no uniform international standards for the nomenclature of this entity. This consensus document, commissioned by the International Society of Heart and Lung Transplantation Board, is based on best evidence and clinical consensus derived from critical analysis of available information pertaining to angiography, intravascular ultrasound imaging, microvascular function, cardiac allograft histology, circulating immune markers, non-invasive imaging tests, and gene-based and protein-based biomarkers. This document represents a working formulation for an international nomenclature of cardiac allograft vasculopathy, similar to the development of the system for adjudication of cardiac allograft rejection by histology. PMID:20620917

  14. Genomic profiling of lung adenocarcinoma patients reveals therapeutic targets and confers clinical benefit when standard molecular testing is negative

    PubMed Central

    Lim, Sun Min; Kim, Eun Young; Kim, Hye Ryun; Ali, Siraj M.; Greenbowe, Joel R.; Shim, Hyo Sup; Chang, Hyun; Lim, Seungtaek; Paik, Soonmyung; Cho, Byoung Chul

    2016-01-01

    Background: Identification of clinically relevant oncogenic drivers in advanced cancer is critical in selecting appropriate targeted therapy. Using next-generation sequencing (NGS)-based clinical cancer gene assay, we performed comprehensive genomic profiling (CGP) of advanced cases of lung adenocarcinoma. Methods: Formalin-fixed paraffin-embedded tumors from 51 lung adenocarcinoma patients whose tumors previously tested negative for EGFR/KRAS/ALK by conventional methods were collected, and CGP was performed via hybridization capture of 4,557 exons from 287 cancer-related genes and 47 introns from 19 genes frequently rearranged in cancer. Results: Genomic profiles of all 51 cases were obtained, with a median coverage of 564x and a total of 190 individual genomic alterations (GAs). GAs per specimen was a mean of 3.7 (range 0-10).Cancer genomes are characterized by 50% (80/190) non-synonymous base substitutions, 15% (29/190) insertions or deletion, and 3% (5/190) splice site mutation. TP53 mutation was the most common GAs (15%, n=29/190), followed by CDKN2A homozygous loss (5%, n=10/190), KRAS mutation (4%, n=8/190), EGFR mutation (4%, n=8/190) and MDM2 amplification (2%, n=5/190). As per NCCN guidelines, targetable GAs were identified in 16 patients (31%) (BRAF mutation [n=1], EGFR mutation [n=8], ERBB2 mutation [n=4], MET amplification [n=1], KIF5B-RET rearrangement [n=2], CCDC6-RET rearrangement [n=1], CD74-ROS1 rearrangement [n=1], EZR-ROS1 rearrangement [n=5], and SLC34A2-ROS1 rearrangement [n=1]). Conclusion: Fifty eight percent of patients wild type by standard testing for EGFR/KRAS/ALK have GAs identifiable by CGP that suggest benefit from target therapy. CGP used when standard molecular testing for NSCLC is negative can reveal additional avenues of benefit from targeted therapy. PMID:26992220

  15. Real-Time Imaging of Resident T Cells in Human Lung and Ovarian Carcinomas Reveals How Different Tumor Microenvironments Control T Lymphocyte Migration.

    PubMed

    Bougherara, Houcine; Mansuet-Lupo, Audrey; Alifano, Marco; Ngô, Charlotte; Damotte, Diane; Le Frère-Belda, Marie-Aude; Donnadieu, Emmanuel; Peranzoni, Elisa

    2015-01-01

    T cells play a key role in the battle against cancer. To perform their antitumor activities, T cells need to adequately respond to tumor antigens by establishing contacts with either malignant cells or antigen-presenting cells. These latter functions rely on a series of migratory steps that go from entry of T cells into the tumor followed by their locomotion in the tumor stroma. Our knowledge of how T cells migrate within tumors mainly comes from experiments performed in mouse models. Whereas such systems have greatly advanced our understanding, they do not always faithfully recapitulate the disease observed in cancer patients. We previously described a technique based on tissue slices that enables to track with real-time imaging microscopy the motile behavior of fluorescent T cells plated onto fresh sections of human lung tumors. We have now refined this approach to monitor the locomotion of resident tumor-infiltrating CD8 T cells labeled with fluorescently coupled antibodies. Using this approach, our findings reveal that CD8 T cells accumulate in the stroma of ovarian and lung carcinomas but move slowly in this compartment. Conversely, even though less populated, tumors islets were found to be zones of faster migration for resident CD8 T cells. We also confirm the key role played by collagen fibers, which, by their orientation, spacing and density, control the distribution and migration of resident CD8 T cells within the tumor stroma. We have subsequently demonstrated that, under some physical tissue constraints, CD8 T cells exhibited a mode of migration characterized by alternate forward and backward movements. In sum, using an ex vivo assay to track CD8 T cells in fresh human tumor tissues, we have identified the extracellular matrix as a major stromal component in influencing T cell migration, thereby impacting the control of tumor growth. This approach will aid in the development and testing of novel immunotherapy strategies to promote T cell migration in

  16. Glycogen Synthase Kinase 3 Protein Kinase Activity Is Frequently Elevated in Human Non-Small Cell Lung Carcinoma and Supports Tumour Cell Proliferation

    PubMed Central

    O′Flaherty, Linda; Pardo, Olivier E.; Dzien, Piotr; Phillips, Lois; Morgan, Carys; Pawade, Joya; May, Margaret T.; Sohail, Muhammad; Hetzel, Martin R.; Seckl, Michael J.; Tavaré, Jeremy M.

    2014-01-01

    Background Glycogen synthase kinase 3 (GSK3) is a central regulator of cellular metabolism, development and growth. GSK3 activity was thought to oppose tumourigenesis, yet recent studies indicate that it may support tumour growth in some cancer types including in non-small cell lung carcinoma (NSCLC). We examined the undefined role of GSK3 protein kinase activity in tissue from human NSCLC. Methods The expression and protein kinase activity of GSK3 was determined in 29 fresh frozen samples of human NSCLC and patient-matched normal lung tissue by quantitative immunoassay and western blotting for the phosphorylation of three distinct GSK3 substrates in situ (glycogen synthase, RelA and CRMP-2). The proliferation and sensitivity to the small-molecule GSK3 inhibitor; CHIR99021, of NSCLC cell lines (Hcc193, H1975, PC9 and A549) and non-neoplastic type II pneumocytes was further assessed in adherent culture. Results Expression and protein kinase activity of GSK3 was elevated in 41% of human NSCLC samples when compared to patient-matched control tissue. Phosphorylation of GSK3α/β at the inhibitory S21/9 residue was a poor biomarker for activity in tumour samples. The GSK3 inhibitor, CHIR99021 dose-dependently reduced the proliferation of three NSCLC cell lines yet was ineffective against type II pneumocytes. Conclusion NSCLC tumours with elevated GSK3 protein kinase activity may have evolved dependence on the kinase for sustained growth. Our results provide further important rationale for exploring the use of GSK3 inhibitors in treating NSCLC. PMID:25486534

  17. 78 FR 35549 - Black Lung Benefits Act: Standards for Chest Radiographs

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-13

    ... X-rays in 1980. See 45 FR 13678, 13680-81 (February 29, 1980). Codified at 20 CFR 718.102, 718.202.... SUMMARY: Physicians and adjudicators use chest radiographs (X-rays) as a tool in evaluating whether a coal... update the quality standards applicable to chest radiographs (X-rays) used in diagnosing the existence...

  18. Thrombosis of Kommerell's diverticulum with subclavian steal phenomenon in a patient with non-small cell lung carcinoma under chemotherapy.

    PubMed

    Faggioni, Lorenzo; Gabelloni, Michela; Napoli, Vinicio; Iorio, Francesco; Chella, Antonio; Caramella, Davide

    2016-01-01

    Kommerell's diverticulum (KD) is defined as a bulbous dilatation of the origin of an aberrant subclavian artery due to a remnant of the left fourth aortic arch. We report the case of an asymptomatic woman in whom progressive thrombosis of the KD extending to the prevertebral tract of an aberrant right subclavian artery was detected at multidetector computed tomography imaging for lung cancer staging performed before and after the beginning of chemotherapy. Reversed blood flow in the ipsilateral vertebral artery due to subclavian steal phenomenon was also observed by color Doppler ultrasound examination.

  19. Licoricidin, an Active Compound in the Hexane/Ethanol Extract of Glycyrrhiza uralensis, Inhibits Lung Metastasis of 4T1 Murine Mammary Carcinoma Cells

    PubMed Central

    Park, So Young; Kwon, Soo Jin; Lim, Soon Sung; Kim, Jin-Kyu; Lee, Ki Won; Park, Jung Han Yoon

    2016-01-01

    Licorice extracts containing glycyrrhizin exhibit anti-carcinogenic properties. Because glycyrrhizin induces severe hypokalemia and hypertension, we prepared a hexane/ethanol extract of Glycyrrhiza uralensis (HEGU) that lacks glycyrrhizin, and showed that HEGU induces apoptosis and G1 cell cycle arrest and inhibits migration of DU145 human prostate cancer cells. Our previous in vitro studies identified two active components in HEGU: isoangustone A, which induces apoptosis and G1 cycle arrest, and licoricidin, which inhibits metastasis. This study examined whether HEGU and licoricidin inhibit metastasis using the 4T1 mammary cancer model. Both HEGU and licoricidin treatment reduced pulmonary metastasis and the expression of CD45, CD31, HIF-1α, iNOS, COX-2, and VEGF-A in tumor tissues. Additionally, a decrease in protein expression of VEGF-R2, VEGF-C, VEGF-R3, and LYVE-1 was noted in tumor tissues of licoricidin-treated mice. Furthermore, the blood concentrations of MMP-9, ICAM-1, VCAM-1, and VEGF-A were decreased in HEGU-treated mice. In vitro 4T1 cell culture results showed that both HEGU and licoricidin inhibited cell migration, MMP-9 secretion, and VCAM expression. The present study demonstrates that the licoricidin in HEGU inhibits lung metastasis of 4T1 mammary carcinoma cells, which may be mediated via inhibition of cancer cell migration, tumor angiogenesis, and lymphangiogenesis. PMID:27314329

  20. Licoricidin, an Active Compound in the Hexane/Ethanol Extract of Glycyrrhiza uralensis, Inhibits Lung Metastasis of 4T1 Murine Mammary Carcinoma Cells.

    PubMed

    Park, So Young; Kwon, Soo Jin; Lim, Soon Sung; Kim, Jin-Kyu; Lee, Ki Won; Park, Jung Han Yoon

    2016-01-01

    Licorice extracts containing glycyrrhizin exhibit anti-carcinogenic properties. Because glycyrrhizin induces severe hypokalemia and hypertension, we prepared a hexane/ethanol extract of Glycyrrhiza uralensis (HEGU) that lacks glycyrrhizin, and showed that HEGU induces apoptosis and G1 cell cycle arrest and inhibits migration of DU145 human prostate cancer cells. Our previous in vitro studies identified two active components in HEGU: isoangustone A, which induces apoptosis and G1 cycle arrest, and licoricidin, which inhibits metastasis. This study examined whether HEGU and licoricidin inhibit metastasis using the 4T1 mammary cancer model. Both HEGU and licoricidin treatment reduced pulmonary metastasis and the expression of CD45, CD31, HIF-1α, iNOS, COX-2, and VEGF-A in tumor tissues. Additionally, a decrease in protein expression of VEGF-R2, VEGF-C, VEGF-R3, and LYVE-1 was noted in tumor tissues of licoricidin-treated mice. Furthermore, the blood concentrations of MMP-9, ICAM-1, VCAM-1, and VEGF-A were decreased in HEGU-treated mice. In vitro 4T1 cell culture results showed that both HEGU and licoricidin inhibited cell migration, MMP-9 secretion, and VCAM expression. The present study demonstrates that the licoricidin in HEGU inhibits lung metastasis of 4T1 mammary carcinoma cells, which may be mediated via inhibition of cancer cell migration, tumor angiogenesis, and lymphangiogenesis. PMID:27314329

  1. Baicalein Induces Caspase-dependent Apoptosis Associated with the Generation of ROS and the Activation of AMPK in Human Lung Carcinoma A549 Cells.

    PubMed

    Kim, Hong Jae; Park, Cheol; Han, Min-Ho; Hong, Su-Hyun; Kim, Gi-Young; Hong, Sang Hoon; Kim, Nam Deuk; Choi, Yung Hyun

    2016-03-01

    Baicalein is one of the main bioactive flavonoids found in the roots of Scutellaria baicalensis Georgi. Here, we report that baicalein-induced growth inhibition was associated with the induction of apoptosis in human lung carcinoma A549 cells. Baicalein stimulated the expression of DR5, FasL, and FADD, and activated caspase-8 by reducing the levels of FLIPs (FLICE-inhibitory proteins). The apoptotic cell death was also connected with an activation of caspase-9 and -3, and cleavage of poly(ADP-ribose) polymerase; however, a blockage of caspase activation abolished baicalein-induced apoptotic potentials. Additionally, baicalein caused a mitochondrial membrane potential (MMP), the truncation of Bid, and the translocation of pro-apoptotic Bax to the mitochondria, thereby inducing the release of cytochrome c into the cytosol. In turn, baicalein increased the generation of reactive oxygen species (ROS); however, an ROS scavenger, N-acetylcysteine, notably attenuated baicalein-mediated loss of MMP and activation of caspases. Furthermore, baicalein activated the AMP-activated protein kinase (AMPK) signaling pathway. Consequently, baicalein-triggered cell death was attenuated by an AMPK inhibitor, but increased by an AMPK activator, compound C. Overall, the results suggest that the apoptotic activity of baicalein may be associated with caspase-dependent cascade through the activation of both intrinsic and extrinsic signaling pathways connected with ROS generation and AMPK activation.

  2. Growth arrest of lung carcinoma cells (A549) by polyacrylate-anchored peroxovanadate by activating Rac1-NADPH oxidase signalling axis.

    PubMed

    Chatterjee, Nirupama; Anwar, Tarique; Islam, Nashreen S; Ramasarma, T; Ramakrishna, Gayatri

    2016-09-01

    Hydrogen peroxide is often required in sublethal, millimolar concentrations to show its oxidant effects on cells in culture as it is easily destroyed by cellular catalase. Previously, we had shown that diperoxovanadate, a physiologically stable peroxovanadium compound, can substitute H2O2 effectively in peroxidation reactions. We report here that peroxovanadate when anchored to polyacrylic acid (PAPV) becomes a highly potent inhibitor of growth of lung carcinoma cells (A549). The early events associated with PAPV treatment included cytoskeletal modifications, increase in GTPase activity of Rac1, accumulation of the reactive oxygen species, and also increase in phosphorylation of H2AX (γH2AX), a marker of DNA damage. These effects persisted even at 24 h after removal of the compound and culminated in increased levels of p53 and p21 together with growth arrest. The PAPV-mediated growth arrest was significantly abrogated in cells pre-treated with the N-acetylcysteine, Rac1 knocked down by siRNA and DPI an inhibitor of NADPH oxidase. In conclusion, our results show that polyacrylate derivative of peroxovanadate efficiently arrests growth of A549 cancerous cells by activating the axis of Rac1-NADPH oxidase leading to oxidative stress and DNA damage. PMID:27435854

  3. Baicalein Induces Caspase-dependent Apoptosis Associated with the Generation of ROS and the Activation of AMPK in Human Lung Carcinoma A549 Cells.

    PubMed

    Kim, Hong Jae; Park, Cheol; Han, Min-Ho; Hong, Su-Hyun; Kim, Gi-Young; Hong, Sang Hoon; Kim, Nam Deuk; Choi, Yung Hyun

    2016-03-01

    Baicalein is one of the main bioactive flavonoids found in the roots of Scutellaria baicalensis Georgi. Here, we report that baicalein-induced growth inhibition was associated with the induction of apoptosis in human lung carcinoma A549 cells. Baicalein stimulated the expression of DR5, FasL, and FADD, and activated caspase-8 by reducing the levels of FLIPs (FLICE-inhibitory proteins). The apoptotic cell death was also connected with an activation of caspase-9 and -3, and cleavage of poly(ADP-ribose) polymerase; however, a blockage of caspase activation abolished baicalein-induced apoptotic potentials. Additionally, baicalein caused a mitochondrial membrane potential (MMP), the truncation of Bid, and the translocation of pro-apoptotic Bax to the mitochondria, thereby inducing the release of cytochrome c into the cytosol. In turn, baicalein increased the generation of reactive oxygen species (ROS); however, an ROS scavenger, N-acetylcysteine, notably attenuated baicalein-mediated loss of MMP and activation of caspases. Furthermore, baicalein activated the AMP-activated protein kinase (AMPK) signaling pathway. Consequently, baicalein-triggered cell death was attenuated by an AMPK inhibitor, but increased by an AMPK activator, compound C. Overall, the results suggest that the apoptotic activity of baicalein may be associated with caspase-dependent cascade through the activation of both intrinsic and extrinsic signaling pathways connected with ROS generation and AMPK activation. PMID:26971531

  4. p53 immunolabeling in archival paraffin-embedded tissues: optimal protocol based on microwave heating for eight antibodies on lung carcinomas.

    PubMed

    Tenaud, C; Negoescu, A; Labat-Moleur, F; Legros, Y; Soussi, T; Brambilla, E

    1994-10-01

    The prognostic value of p53 gene mutations is dealt with by several recent reports. However, retrospective assessment of p53 tumor status on archived samples has been prevented by p53 epitope alteration during routine fixation and embedding procedures. This study aimed at establishing a reproducible low-cost protocol to retrieve not only N-terminal, but also midregion and C-terminal, epitopes, with special attention to possible artifacts induced by epitope retrieval procedures. Using microwave heating, we compared the epitope retrieval efficiency of five solutions with eight commercial antibodies on 21 lung carcinomas for which frozen tissue and samples fixed with formalin and Bouin's liquid were available. All eight epitopes were retrieved, citrate buffer proving efficient for seven. PAb 240 epitope was restored by target unmasking fluid only. No false positivity was observed. Fixation-induced loss of p53 immunoreactivity was minimal for formalin (two of 10 tumors for one antibody each), more significant for Bouin (six of 10 tumors for one to five antibodies). On the other hand, staining intensity was maintained or even improved, and nonspecific staining reduced, through fixation. We conclude that p53 stabilization can be detected on routinely processed archival tumor samples with a reliability similar to that of frozen tissue by means of a microwave-based procedure and a panel of at least three antibodies, with epitopes on the N-terminal, C-terminal, and midpart of the molecule.

  5. Identification and Pharmacological Analysis of High Efficacy Small Molecule Inhibitors of EGF-EGFR Interactions in Clinical Treatment of Non-Small Cell Lung Carcinoma: a Computational Approach.

    PubMed

    Gudala, Suresh; Khan, Uzma; Kanungo, Niteesh; Bandaru, Srinivas; Hussain, Tajamul; Parihar, Ms; Nayarisseri, Anuraj; Mundluru, Hema Prasad

    2015-01-01

    Inhibition of EGFR-EGF interactions forms an important therapeutic rationale in treatment of non-small cell lung carcinoma. Established inhibitors have been successful in reducing proliferative processes observed in NSCLC, however patients suffer serious side effects. Considering the narrow therapeutic window of present EGFR inhibitors, the present study centred on identifying high efficacy EGFR inhibitors through structure based virtual screening strategies. Established inhibitors - Afatinib, Dacomitinib, Erlotinib, Lapatinib, Rociletinib formed parent compounds to retrieve similar compounds by linear fingerprint based tanimoto search with a threshold of 90%. The compounds (parents and respective similars) were docked at the EGF binding cleft of EGFR. Patch dock supervised protein-protein interactions were established between EGF and ligand (query and similar) bound and free states of EGFR. Compounds ADS103317, AKOS024836912, AGN-PC-0MXVWT, GNF-Pf-3539, SCHEMBL15205939 were retrieved respectively similar to Afatinib, Dacomitinib, Erlotinib, Lapatinib, Rociletinib. Compound- AGN-PC-0MXVWT akin to Erlotinib showed highest affinity against EGFR amongst all the compounds (parent and similar) assessed in the study. Further, AGN-PC-0MXVWT brought about significant blocking of EGFR-EGF interactions in addition showed appreciable ADMET properties and pharmacophoric features. In the study, we report AGN-PC-0MXVWT to be an efficient and high efficacy inhibitor of EGFR-EGF interactions identified through computational approaches.

  6. The histone deacetylase inhibitor SAHA induces HSP60 nitration and its extracellular release by exosomal vesicles in human lung-derived carcinoma cells

    PubMed Central

    Bavisotto, Celeste Caruso; Barone, Rosario; Emanuele, Sonia; Lo Cascio, Filippa; Mocciaro, Emanuele; Fais, Stefano; De Macario, Everly Conway; Macario, Alberto J.L.; Cappello, Francesco; Lauricella, Marianna

    2016-01-01

    HSP60 undergoes changes in quantity and distribution in some types of tumors suggesting a participation of the chaperonin in the mechanism of transformation and cancer progression. Suberoylanilide hydroxamic acid (SAHA), a member of a family of histone deacetylase inhibitors (HDACi), has anti-cancer potential but its interaction, if any, with HSP60 has not been elucidated. We investigated the effects of SAHA in a human lung-derived carcinoma cell line (H292). We analysed cell viability and cycle; oxidative stress markers; mitochondrial integrity; HSP60 protein and mRNA levels; and HSP60 post-translational modifications, and its secretion. We found that SAHA is cytotoxic for H292 cells, interrupting the cycle at the G2/M phase, which is followed by death; cytotoxicity is associated with oxidative stress, mitochondrial damage, and diminution of intracellular levels of HSP60; HSP60 undergoes a post-translational modification and becomes nitrated; and nitrated HSP60 is exported via exosomes. We propose that SAHA causes ROS overproduction and mitochondrial dysfunction, which leads to HSP60 nitration and release into the intercellular space and circulation to interact with the immune system. These successive steps might constitute the mechanism of the anti-tumor action of SAHA and provide a basis to design supplementary therapeutic strategies targeting HSP60, which would be more efficacious than the compound alone. PMID:26700624

  7. Sulphur alters NFκB-p300 cross-talk in favour of p53-p300 to induce apoptosis in non-small cell lung carcinoma.

    PubMed

    Saha, Shilpi; Bhattacharjee, Pushpak; Guha, Deblina; Kajal, Kirti; Khan, Poulami; Chakraborty, Sreeparna; Mukherjee, Shravanti; Paul, Shrutarshi; Manchanda, Rajkumar; Khurana, Anil; Nayak, Debadatta; Chakrabarty, Rathin; Sa, Gaurisankar; Das, Tanya

    2015-08-01

    Adverse side effects of chemotherapy during cancer treatment have shifted considerable focus towards therapies that are not only targeted but are also devoid of toxic side effects. We evaluated the antitumorigenic activity of sulphur, and delineated the molecular mechanisms underlying sulphur-induced apoptosis in non-small cell lung carcinoma (NSCLC) cells. A search for the underlying mechanism revealed that the choice between the two cellular processes, NFκBp65-mediated survival and p53-mediated apoptosis, was decided by the competition for a limited pool of transcriptional coactivator protein p300 in NSCLC cells. In contrast, sulphur inhibited otherwise upregulated survival signaling in NSCLC cells by perturbing the nuclear translocation of p65NFκB, its association with p300 histone acetylase, and subsequent transcription of Bcl-2. Under such anti-survival condition, induction of p53-p300 cross-talk enhanced the transcriptional activity of p53 and intrinsic mitochondrial death cascade. Overall, the findings of this preclinical study clearly delineated the molecular mechanism underlying the apoptogenic effect of the non-toxic homeopathic remedy, sulphur, in NSCLC cells.

  8. [Postoperative local thermo-chemotherapy in control of residual pleural diseases after resection of primary lung carcinoma--regulation of dissemination].

    PubMed

    Kodama, K; Doi, O; Tatsuta, M; Kurokawa, E; Terasawa, T

    1987-12-01

    Pleural dissemination was proved by intraoperative histodiagnosis in 11 of 121 patients who underwent pulmonary resection for non-small cell carcinoma of the lung between April, 1985 and December, 1986. To control such intrathoracic residual diseases, we devised a means of local thermo-chemotherapy. Ten of 11 patients were treated with intrapleurally administrated cisplatin (50-100mg, bolus) combined with simultaneous radiofrequency hyperthermia (13.56 MHz) for 2 to 3 weeks after surgery. Courses were repeated at 5-to 7-day intervals. Eight patients had N2-disease, one N1 and the other NX. Eight were adenocarcinomas. Thermal burn of the chest wall with hyperkalemia was observed in only one patient who received thermotherapy at the over a magnetrode power of 450 watts for 50 minutes. In the other 9, side effects were minimal under the thermotherapy to obtain a peripleural temperature beyond 42 degrees C. Of the 10 patients, three lived more than 12 months after treatment. Although distant metastases were recognized in 6 cases, none had local recurrence for the median follow-up period of 6 months. One patient had metastasis to the contralateral supraclavicular lymph nodes. Because there was no evidence of intrathoracic recurrences in this patient, radical neck dissection were performed 15 months after the initial operation. This experience warrants further investigation of thermo-chemotherapy as a treatment for controlling pleural dissemination after resection of primary tumor.

  9. Identification of FGF19 as a prognostic marker and potential driver gene of lung squamous cell carcinomas in Chinese smoking patients

    PubMed Central

    Xia, Weiliang; Li, Ziming; Niu, Xiaomin; Ji, Wenxiang; Yuan, Hong; Xu, Qiang; Luo, Qingquan; Zhang, Jie; Lu, Shun

    2016-01-01

    Comprehensive genomic characterizations of lung squamous cell carcinoma (LSCC) have been performed, but the differences between smokers (S-LSCC) and never smokers (NS-LSCC) are not clear, as NS-LSCC could be considered as a different disease from S-LSCC. In this study we delineated genomic alterations in a cohort of 21 NS-LSCC and 16 S-LSCC patients, and identified common gene mutations and amplifications as previously reported. Inclusion of more NS-LSCC patients enabled us to identify unreported S-LSCC- or NS-LSCC-specific alterations. Importantly, an amplification region containing FGF19, FGF3, FGF4 and CCND1 was found five-times more frequent in S-LSCC than in NS-LSCC. Amplification of FGF19 was validated in independent LSCC samples. Furthermore, FGF19 stimulated LSCC cell growth in vitro. These data implicate FGF19 as a potential driver gene in LSCC with clinic characteristics as smoking. PMID:26943773

  10. Expression of G protein-coupled receptor 56 is associated with tumor progression in non-small-cell lung carcinoma patients

    PubMed Central

    Song, Yanjie; Li, Aiqin; Zhang, Li; Duan, Lingling

    2016-01-01

    Background G protein-coupled receptor 56 (GPR56) is an adhesion G protein-coupled receptor with essential functions for cell physiology and survival, and its expression correlates with prognosis in a number of malignancies. The aim of this study is to determine the relationship of GPR56 expression with clinicopathological parameters and prognosis in non-small-cell lung carcinoma (NSCLC). Methods The levels of GPR56 were evaluated by immunohistochemistry in 157 NSCLC tissue samples. The association between GPR56 and clinicopathological parameters was evaluated by χ2 test. Univariate and multivariate analyses were performed to demonstrate the prognosis role of GPR56. The function of GPR56 in NSCLC cell lines was also explored through overexpression and knockdown studies. Results The expression level of GPR56 in tumor tissues was significantly correlated with the TNM stage of NSCLC (P=0.005). Univariate and multivariate analyses revealed that GPR56 can act as an independent prognostic factor for overall survival. Furthermore, through overexpression and knockdown experiments, we confirmed that GPR56 can promote the proliferation and invasion of NSCLC cells. Conclusion GPR56 plays an important role in tumor development and may serve as a promising target for prognostic prediction in NSCLC. PMID:27462165

  11. MicroRNA-1290 promotes asiatic acid‑induced apoptosis by decreasing BCL2 protein level in A549 non‑small cell lung carcinoma cells.

    PubMed

    Kim, Ki Bbeum; Kim, Karam; Bae, Seunghee; Choi, Yeonghmin; Cha, Hwa Jun; Kim, Soo Yeon; Lee, Jae Ho; Jeon, So Hyeon; Jung, Ho Jung; Ahn, Kyu Joong; An, In-Sook; An, Sungkwan

    2014-09-01

    Asiatic acid, a triterpenoid derived from Centella asiatica, is a putative anticancer agent in several types of cancer cells. Investigations of its biological role in negative regulation of cell growth have focused on the extent of induction of apoptosis in a cell-type-specific manner. In this study, we identified an important regulator of asiatic acid-induced cell death, microRNA (miR)-1290, which sensitizes cells to asiatic acid-induced cytotoxicity and negatively regulates BCL2 expression. Asiatic acid significantly upregulated miR-1290, and asiatic acid-induced cell death was shown to be dependent on miR-1290 activity. Molecular assays demonstrated that BCL2 mRNA is a direct target of miR-1290-mediated RNA interference. The results of functional studies suggest that miR-1290 suppresses cell viability and cell cycle progression. These data provide insight into miR-1290-mediated cellular mechanisms in asiatic acid-treated A549 non-small cell lung carcinoma cells. PMID:25016979

  12. Recurrence and death in non-small cell lung carcinomas: a prognostic model using pathological parameters, microvessel count, and gene protein products.

    PubMed

    Fontanini, G; Vignati, S; Bigini, D; Mussi, A; Lucchi, M; Chiné, S; Angeletti, C A; Bevilacqua, G

    1996-06-01

    The 5-year survival rate of non-small cell lung carcinoma (NSCLC) has only marginally improved during the past two decades, despite advances in surgery and chemoradiotherapy. Major efforts are currently directed toward biological characterization of these tumors to define biomarkers able to add further prognostic information, thus improving new therapeutic protocols. We analyzed the predictive relevance of the microvessel count (MC), bcl-2 and p53 proteins, proliferative activity, and usual postsurgical parameters on recurrence and overall survival in a series of 70 patients with NSCLC. The expression of biological parameters (p53, bcl-2, proliferative activity, and MC) was detected using immunohistochemistry on paraffin-embedded and frozen sections from the tumors treated with surgical resection alone until relapse. In the univariate analysis, the histotype, tumor status, node status, p53, bcl-2, and MC have been shown to significantly affect progression and death. In the multiple logistic regression analysis, the MC (P < 0.000001), tumor status (P < 0.005), and node status (P < 0.0002) influenced the overall survival while prediction of relapse was strongly revealed by tumor status (P < 0.005), nodal metastatic involvement (P < 0.000001), and the assessment of the vascular count (P < 0.0004). These data have allowed the creation of a multivariate model which may add more information on risk of recurrence and death in patients with NSCLC and can form the basis for future randomized clinical trials.

  13. Establishment of a novel small cell lung carcinoma cell line with specific recoverin expression from a patient with cancer-associated retinopathy.

    PubMed

    Kobayashi, Makoto; Ikezoe, Takayuki; Uemura, Yoshiki; Takeuchi, Tamotsu; Ueno, Hisayuki; Ohtsuki, Yuji; Taguchi, Hirokuni

    2007-06-01

    We analysed the biologic properties of a small cell lung carcinoma cell line (designated KK0206) established from a patient with SCLC who had cancer-associated retinopathy (CAR). Morphological and immunohistochemical studies showed that KK0206 cells have features of the classic type of SCLC. KK0206 cells grew in suspension, forming relatively small clumps of cells with a doubling time of 72 h. On light microscopy, the cells were relatively small with little cytoplasm. On immunohistochemistry using anti-bovine recoverin rabbit antibody, the cells were intensely positive for recoverin. In addition, they were positive for NSE, Ki-67, and TP53. They also expressed human recoverin, a photoreceptor protein, whose presence was confirmed by RT-PCR analysis with cDNA sequencing and Western blot analysis. The point mutation of their TP53 gene (exon 156) was detected as well. The present study demonstrates that human recoverin is expressed in SCLC cells cultured from an anti-recoverin antibody-negative patient with CAR. KK0206 might be important for further research on SCLC related retinopathy.

  14. Induction of the endoplasmic reticulum stress and autophagy in human lung carcinoma A549 cells by anacardic acid.

    PubMed

    Seong, Yeong-Ae; Shin, Pyung-Gyun; Yoon, Jin-Soo; Yadunandam, Anandam Kasin; Kim, Gun-Do

    2014-03-01

    Anacardic acid (AA, 2-hydroxy-6-pentadecylbenzoic acid), a constituent of the cashew-nut shell, has a variety of beneficial effects on the treatment of cancer and tumors. However, the fact that AA induces ER stress and autophagy in cancer cell is not known. We investigated the effect of AA on ER-stress and autophagy-induced cell death in cancer cells. Because of our interest in lung cancer, we used the non-small cell lung adenocarcinoma A549 cells treated with 3.0 μg/ml of AA for this research. In this research we found that AA induces intracellular Ca(2+) mobilization and ER stress. AA induced the ER stress-inducing factors, especially IRE1α, and the hallmarks of UPR, Grp78/Bip and GADD153/CHOP. AA inhibited the expression of p-PERK and its downstream substrate, p-elF2α. We also demonstrated that AA induces autophagy. Up-regulation of autophagy-related genes and the appearance of autophagosome in transfected cells with green fluorescent protein (GFP)-LC3 and GFP-Beclin1 plasmids showed the induction of autophagy in AA-treated A549 cells. The morphological analysis of intracellular organelles by TEM also showed the evidence that AA induces ER stress and autophagy. For the first time, our research showed that AA induces ER stress and autophagy in cancer cells. PMID:23955513

  15. Patient with Small Cell Lung Carcinoma and Suspected Right Upper Lobe Abscess Presenting with a Purulent Pericardial Effusion

    PubMed Central

    Goel, Khushboo; Ateeli, Huthayfa; Ampel, Neil M.; L’heureux, Dena

    2016-01-01

    Patient: Male, 61 Final Diagnosis: Streptococcus pneumoniae pericarditis Symptoms: — Medication: — Clinical Procedure: Pericardiocentesis Specialty: Critical Care Medicine Objective: Rare disease Background: Cardiac tamponade caused by pericardial effusion has a high mortality rate; thus, it is important to diagnose and treat this condition immediately. Specifically, bacterial pericarditis, although now very rare, is often fatal because of its fulminant process. Case Report: We present a case of a 61-year-old man with metastatic small cell lung cancer undergoing chemotherapy who presented with fatigue, poor appetite, and altered mental status. He was found to have a large-volume pericardial effusion with tamponade physiology. He underwent emergent pericardiocentesis. The pericardial effusion was nonmalignant, with cultures growing Streptococcus pneumoniae. It was only after his emergent pericardiocentesis that previous imaging from one month prior was able to be reviewed, which showed possible right upper lobe abscess. Conclusions: Most pericardial effusions in cancer patients are related to their malignancy, either due to direct metastasis or secondary physiologic effects. This case is a unique example of a lung cancer patient presenting with a pneumococcal pericardial effusion, which in itself is a rare phenomenon. This case report demonstrates the importance of considering early antibiotic therapy in patients presenting with pericardial effusion, especially given the high mortality rates of infectious pericardial effusions. PMID:27443973

  16. 67-Kilodalton laminin receptor expression correlates with worse prognostic indicators in non-small cell lung carcinomas.

    PubMed

    Fontanini, G; Vignati, S; Chiné, S; Lucchi, M; Mussi, A; Angeletti, C A; Ménard, S; Castronovo, V; Bevilacqua, G

    1997-02-01

    Tumor samples obtained from 72 patients resected for non-small cell lung cancer were stained immunohistochemically using an immunoperoxidase method and the MLuC5 monoclonal antibody specific for the 67-kDa laminin receptor. Sixty-one of 72 patients (84.7%) displayed a MLuC5-positive reaction, which was usually localized in both the inner surface of the plasmatic membranes and the cytoplasm of neoplastic cells. When we compared the laminin receptor expression with clinicopathological and biological parameters such as histotype, grading, T status, N status, ploidy, proliferative activity, vessel invasion, and p53 protein accumulation, the following results were observed: (a) the mean expression of the receptor was higher in the group of patients with metastatic nodal involvement than in those with uninvolved lymph nodes (P = 0.02); (b) a high Ki-67 score (>13% of positive cells) was observed in tumors with a higher mean value of laminin receptor (P = 0.004); (c) the tumors harboring neoplastic emboli in their vessels showed a higher laminin receptor immunoreactivity (P = 0.02); and (d) a borderline association was found between the high mean value of laminin receptor immunopositivity and p53 accumulation in neoplastic cell nuclei (P = 0.05). Our observations indicate that detection of high tissue levels of 67-kDa laminin receptor is associated with an invasive phenotype in non-small cell lung cancer and may provide further information in the biological characterization of this type of cancer.

  17. Comparison of primary lung tumor incidences in the rat evaluated by the standard microscopy method and by multiple step sections.

    PubMed

    Kolling, Angelika; Ernst, Heinrich; Rittinghausen, Susanne; Heinrich, Uwe; Pott, Friedrich

    2008-08-01

    The data presented in this paper have been derived from a carcinogenicity experiment with rats as part of a comprehensive research project focused on experimental studies on the toxicity and carcinogenicity of intratracheally instilled granular dusts [Ernst H, Rittinghausen S, Bartsch W, Creutzenberg O, Dasenbrock C, Görlitz B-D et al. Pulmonary inflammation in rats after intratracheal instillation of quartz, amorphous SiO(2), carbon black, and coal dust and the influence of poly-2-vinylpyridine-N-oxide (PVNO). Exp Toxicol Pathol 2002; 54: 109-26; Ernst H, Kolling A, Bellmann B, Rittinghausen S, Heinrich U, Pott F. Pathogenetische und immunbiologische Untersuchungen zur Frage: Ist die Extrapolation der Staubkanzerogenität von der Ratte auf den Menschen gerechtfertigt? Teil II: Histologie. Abschlussbericht. Umweltforschungsplan des Bundesministeriums für Umwelt, Naturschutz und Reaktorsicherheit. November 2005. http://www.umweltdaten.de/publikationen/fpdf-l/3033.pdf]. The results of the standard approach to histological sampling in rodent carcinogenicity inhalation studies were compared to those obtained after supplemental evaluation of step sections at intervals of 250microm through the entire lung. Seven lung tissue specimens (six sections) each of 251 rats (55 rats of the control group, 53 rats of the group treated with quartz DQ 12, 56 rats of the group treated with quartz DQ 12 and PVNO (poly-2-vinylpyridine-N-oxide), 53 rats of the group treated with amorphous SiO(2), and 17 rats each of the groups treated with coal dust and carbon black) were evaluated by light microscopy. At least 60 hematoxylin and eosin (H&E)-stained sections per lung were evaluated of 99 female rats (30 rats of the control group, 7 rats each of the groups treated with quartz, quartz and PVNO, and carbon black, 31 rats of the group treated with amorphous SiO(2), and 17 rats treated with coal dust). For the neoplastic and pre-neoplastic lesions detected in the serial slides an

  18. TG4010 and Nivolumab in Patients With Lung Cancer

    ClinicalTrials.gov

    2016-07-07

    Recurrent Non-Small Cell Lung Carcinoma; Stage I Non-Small Cell Lung Cancer; Stage II Non-Small Cell Lung Cancer; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Non-Small Cell Lung Cancer

  19. Endostatin enhances antitumor effect of tumor antigen-pulsed dendritic cell therapy in mouse xenograft model of lung carcinoma

    PubMed Central

    Liang, Jing; Liu, Xiaolin; Xie, Qi; Chen, Guoling; Li, Xingyu; Jia, Yanrui; Yin, Beibei; Qu, Xun; Li, Yan

    2016-01-01

    Objective To investigate the antitumor effect of endostatin combined with tumor antigen-pulsed dendritic cell (DC)-T cell therapy on lung cancer. Methods Transplanted Lewis lung cancer (LLC) models of C57BL/6 mice were established by subcutaneous injection of LLC cells in left extremity axillary. Tumor antigen-pulsed DC-T cells from spleen cells and bone of mice were cultured in vitro. Tumor-bearing mice were randomly divided into three groups, including DC-T+endostatin group, DC-T group, and phosphate-buffered saline (PBS) control group. Microvessel density (MVD) of tumor tissue in tumor-bearing mice was determined by immunohistochemistry (IHC). The expressions of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α (HIF-1α) were determined by Western blotting and IHC staining. The proportions of CD8+ T cells, mature dendritic cells (mDC), tumor-associated macrophages [TAM (M1/M2)], and myeloid-derived suppressor cells (MDSC) in suspended cells of tumor tissue were determined by flow cytometry. The expressions of interleukin (IL)-6, IL-10, IL-17, transforming growth factor-β (TGF-β) and interferon-γ (IFN-γ) in suspended cells of tumor tissue were detected by enzyme-linked immune sorbent assay (ELISA). Results DC-T cells combined with endostatin remarkably suppressed tumor growth. MVD of mice in DC-T+endostatin group was significantly lower than that of the control group and DC-T monotherapy group. The expressions of VEGF, IL-6 and IL-17 in tumors were markedly decreased, but IFN-γ and HIF-1α increased after treating with DC-T cells combined with endostatin, compared to control group and DC-T group. In the DC-T+endostatin group, the proportions of MDSC and TAM (M2 type) were significantly decreased, mDC and TAM (M1 type) were up-regulated, and CD8+ T cells were recruited to infiltrate tumors, in contrast to PBS control and DC-T monotherapy. DC-T cells combined with endostatin potently reduced the expressions of IL-6, IL-10, TGF-β and

  20. Phase 3 Study of Bavituximab Plus Docetaxel Versus Docetaxel Alone in Patients With Late-stage Non-squamous Non-small-cell Lung Cancer

    ClinicalTrials.gov

    2016-02-01

    Non-Small-Cell Lung Cancer Stage IIIB; Non-Small-Cell Lung Cancer Stage IV; Non-Small-Cell Lung Cancer Metastatic; Carcinoma, Non-Small-Cell Lung; Non-Small Cell Lung Cancer; Non-Small-Cell Lung Carcinoma; Nonsmall Cell Lung Cancer

  1. Screening for lung cancer.

    PubMed Central

    Carter, D.

    1981-01-01

    The survival from bronchogenic carcinoma is highly dependent upon stage at the time of treatment. This is particularly true for squamous cell carcinoma, adenocarcinoma, and large cell carcinoma, but holds true for small cell carcinoma as well. The problem presented to the medical profession has been to find a practical means of detecting lung cancer while it is still at an early stage. Three studies in progress have indicated that a larger proportion of the patients may be found to have early stage lung cancer when screened with a combination of chest X-rays and sputum cytology. However, the detection of these early stage cases has not yet been translated into an improvement in the overall mortality rate from lung cancer. PMID:6278787

  2. Molecular docking studies of Traditional Chinese Medicinal compounds against known protein targets to treat non-small cell lung carcinomas

    PubMed Central

    Zhao, Guo-Fang; Huang, Zuo-An; Du, Xue-Kui; Yang, Ming-Lei; Huang, Dan-Dan; Zhang, Shun

    2016-01-01

    In silico drug design using virtual screening, absorption, distribution, metabolism and excretion (ADME)/Tox data analysis, automated docking and molecular dynamics simulations for the determination of lead compounds for further in vitro analysis is a cost effective strategy. The present study used this strategy to discover novel lead compounds from an in-house database of Traditional Chinese Medicinal (TCM) compounds against epithelial growth factor receptor (EGFR) protein for targeting non-small cell lung cancer (NSCLC). After virtual screening of an initial dataset of 2,242 TCM compounds, leads were identified based on binding energy and ADME/Tox data and subjected to automated docking followed by molecular dynamics simulation. Triptolide, a top compound identified by this vigorous in silico screening, was then tested in vitro on the H2347 cell line carrying wild-type EGFR, revealing an anti-proliferative potency similar to that of known drugs against NSCLC. PMID:27279494

  3. The results with the addition of metronomic cyclophosphamide to palliative radiotherapy for the treatment of non-small cell lung carcinoma

    PubMed Central

    Joshi, Subhash Chandra; Pandey, Kailash Chandra; Rastogi, Madhup; Sharma, Mukesh; Gupta, Manoj

    2015-01-01

    Background A considerable proportion of non-small cell lung carcinoma (NSCLC) patients are ineligible for radical therapies. Many are frail not to tolerate intravenous palliative chemotherapy either. These patients often receive palliative radiotherapy (RT), or supportive care alone. We intend to compare outcomes with palliative RT alone, versus palliative RT plus oral low dose metronomic cyclophosphamide. Methods Data was mined from 139 eligible NSCLC patient records. Comparisons were made between 65 patients treated from January 2011 to March 2013 with palliative RT (20-30 Gray in 5-10 fractions) alone, versus 74 patients treated from April 2013 to December 2014 with palliative RT plus oral metronomic cyclophosphamide (50 mg once daily from day of initiation of RT until at least the day of disease progression). Response was assessed after 1-month post-RT by computed tomography. Patients with complete or partial response were recorded as responders. For the determination of progression free survival (PFS), progression would be declared in case of increase in size of lesions, development of new lesions, or development of effusions. The proportions of responders were compared with the Fisher exact test, and the PFS curves were compared with the log-rank test. Results Differences in response rates were statistically insignificant. The PFS was significantly higher when metronomic chemotherapy was added to RT in comparison to treatment with RT alone (mean PFS 3.1 vs. 2.55 months; P=0.0501). Further histological sub-group analysis revealed that the enhanced outcomes with addition of metronomic cyclophosphamide to RT were limited to patients with adenocarcinoma histology (3.5 vs. 2.4 months; P=0.0053), while there was no benefit for those with squamous cell histology (2.6 vs. 2.6 months; P=1). At the dose of oral cyclophosphamide used, there was no recorded instance of any measurable hematological toxicity. Conclusions For pulmonary adenocarcinoma patients, the treatment

  4. Terminal N-Acetylgalactosamine-Specific Leguminous Lectin from Wisteria japonica as a Probe for Human Lung Squamous Cell Carcinoma

    PubMed Central

    Soga, Keisuke; Teruya, Futaba; Tateno, Hiroaki; Hirabayashi, Jun; Yamamoto, Kazuo

    2013-01-01

    Millettia japonica was recently reclassified into the genus Wisteria japonica based on chloroplast and nuclear DNA sequences. Because the seed of Wisteria floribunda expresses leguminous lectins with unique N-acetylgalactosamine-binding specificity, we purified lectin from Wisteria japonica seeds using ion exchange and gel filtration chromatography. Glycan microarray analysis demonstrated that unlike Wisteria floribunda and Wisteria brachybotrys lectins, which bind to both terminal N-acetylgalactosamine and galactose residues, Wisteria japonica lectin (WJA) specifically bound to both α- and β-linked terminal N-acetylgalactosamine, but not galactose residues on oligosaccharides and glycoproteins. Further, frontal affinity chromatography using more than 100 2-aminopyridine-labeled and p-nitrophenyl-derivatized oligosaccharides demonstrated that the ligands with the highest affinity for Wisteria japonica lectin were GalNAcβ1-3GlcNAc and GalNAcβ1-4GlcNAc, with Ka values of 9.5 × 104 and 1.4 × 105 M-1, respectively. In addition, when binding was assessed in a variety of cell lines, Wisteria japonica lectin bound specifically to EBC-1 and HEK293 cells while other Wisteria lectins bound equally to all of the cell lines tested. Wisteria japonica lectin binding to EBC-1 and HEK293 cells was dramatically decreased in the presence of N-acetylgalactosamine, but not galactose, mannose, or N-acetylglucosamine, and was completely abrogated by β-hexosaminidase-digestion of these cells. These results clearly demonstrate that Wisteria japonica lectin binds to terminal N-acetylgalactosamine but not galactose. In addition, histochemical analysis of human squamous cell carcinoma tissue sections demonstrated that Wisteria japonica lectin specifically bound to differentiated cancer tissues but not normal tissue. This novel binding characteristic of Wisteria japonica lectin has the potential to become a powerful tool for clinical applications. PMID:24349556

  5. Terminal N-acetylgalactosamine-specific leguminous lectin from Wisteria japonica as a probe for human lung squamous cell carcinoma.

    PubMed

    Soga, Keisuke; Teruya, Futaba; Tateno, Hiroaki; Hirabayashi, Jun; Yamamoto, Kazuo

    2013-01-01

    Millettia japonica was recently reclassified into the genus Wisteria japonica based on chloroplast and nuclear DNA sequences. Because the seed of Wisteria floribunda expresses leguminous lectins with unique N-acetylgalactosamine-binding specificity, we purified lectin from Wisteria japonica seeds using ion exchange and gel filtration chromatography. Glycan microarray analysis demonstrated that unlike Wisteria floribunda and Wisteria brachybotrys lectins, which bind to both terminal N-acetylgalactosamine and galactose residues, Wisteria japonica lectin (WJA) specifically bound to both α- and β-linked terminal N-acetylgalactosamine, but not galactose residues on oligosaccharides and glycoproteins. Further, frontal affinity chromatography using more than 100 2-aminopyridine-labeled and p-nitrophenyl-derivatized oligosaccharides demonstrated that the ligands with the highest affinity for Wisteria japonica lectin were GalNAcβ1-3GlcNAc and GalNAcβ1-4GlcNAc, with K(a) values of 9.5 × 10(4) and 1.4 × 10(5) M(-1), respectively. In addition, when binding was assessed in a variety of cell lines, Wisteria japonica lectin bound specifically to EBC-1 and HEK293 cells while other Wisteria lectins bound equally to all of the cell lines tested. Wisteria japonica lectin binding to EBC-1 and HEK293 cells was dramatically decreased in the presence of N-acetylgalactosamine, but not galactose, mannose, or N-acetylglucosamine, and was completely abrogated by β-hexosaminidase-digestion of these cells. These results clearly demonstrate that Wisteria japonica lectin binds to terminal N-acetylgalactosamine but not galactose. In addition, histochemical analysis of human squamous cell carcinoma tissue sections demonstrated that Wisteria japonica lectin specifically bound to differentiated cancer tissues but not normal tissue. This novel binding characteristic of Wisteria japonica lectin has the potential to become a powerful tool for clinical applications. PMID:24349556

  6. Stereotactic Body Radiation Therapy for Early-Stage Non-Small-Cell Lung Carcinoma: Four-Year Results of a Prospective Phase II Study

    SciTech Connect

    Fakiris, Achilles J.; McGarry, Ronald C.; Yiannoutsos, Constantin T.; Papiez, Lech; Williams, Mark; Henderson, Mark A.; Timmerman, Robert

    2009-11-01

    Purpose: The 50-month results of a prospective Phase II trial of stereotactic body radiation therapy (SBRT) in medically inoperable patients are reported. Methods and Materials: A total of 70 medically inoperable patients had clinically staged T1 (34 patients) or T2 (36 patients) (<=7 cm), N0, M0, biopsy-confirmed non-small-cell lung carcinoma (NSCLC) and received SBRT as per our previously published reports. The SBRT treatment dose of 60-66 Gy was prescribed to the 80% isodose volume in three fractions. Results: Median follow-up was 50.2 months (range, 1.4-64.8 months). Kaplan-Meier local control at 3 years was 88.1%. Regional (nodal) and distant recurrence occurred in 6 (8.6%) and 9 (12.9%) patients, respectively. Median survival (MS) was 32.4 months and 3-year overall survival (OS) was 42.7% (95% confidence interval [95% CI], 31.1-54.3%). Cancer-specific survival at 3 years was 81.7% (95% CI, 70.0-93.4%). For patients with T1 tumors, MS was 38.7 months (95% CI, 25.3-50.2) and for T2 tumors MS was 24.5 months (95% CI, 18.5-37.4) (p = 0.194). Tumor volume (<=5 cc, 5-10 cc, 10-20 cc, >20 cc) did not significantly impact survival: MS was 36.9 months (95% CI, 18.1-42.9), 34.0 (95% CI, 16.9-57.1), 32.8 (95% CI, 21.3-57.8), and 21.4 months (95% CI, 17.8-41.6), respectively (p = 0.712). There was no significant survival difference between patients with peripheral vs. central tumors (MS 33.2 vs. 24.4 months, p = 0.697). Grade 3 to 5 toxicity occurred in 5 of 48 patients with peripheral lung tumors (10.4%) and in 6 of 22 patients (27.3%) with central tumors (Fisher's exact test, p = 0.088). Conclusion: Based on our study results, use of SBRT results in high rates of local control in medically inoperable patients with Stage I NSCLC.

  7. Molecular docking studies of Traditional Chinese Medicinal compounds against known protein targets to treat non-small cell lung carcinomas.

    PubMed

    Zhao, Guo-Fang; Huang, Zuo-An; Du, Xue-Kui; Yang, Ming-Lei; Huang, Dan-Dan; Zhang, Shun

    2016-08-01

    In silico drug design using virtual screening, absorption, distribution, metabolism and excretion (ADME)/Tox data analysis, automated docking and molecular dynamics simulations for the determination of lead compounds for further in vitro analysis is a cost effective strategy. The present study used this strategy to discover novel lead compounds from an in-house database of Traditional Chinese Medicinal (TCM) compounds against epithelial growth factor receptor (EGFR) protein for targeting non-small cell lung cancer (NSCLC). After virtual screening of an initial dataset of 2,242 TCM compounds, leads were identified based on binding energy and ADME/Tox data and subjected to automated docking followed by molecular dynamics simulation. Triptolide, a top compound identified by this vigorous in silico screening, was then tested in vitro on the H2347 cell line carrying wild-type EGFR, revealing an anti-proliferative potency similar to that of known drugs against NSCLC. PMID:27279494

  8. 5-Fluorouracil preferentially sensitizes mutant KRAS non-small cell lung carcinoma cells to TRAIL-induced apoptosis.

    PubMed

    Wang, Haizhen; Yang, Tao; Wu, Xiangwei

    2015-11-01

    Mutations in the KRAS gene are very common in non-small cell lung cancer (NSCLC), but effective therapies targeting KRAS have yet to be developed. Interest in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a potent inducer of cell death, has increased following the observation that TRAIL can selectively kill a wide variety of human cancer cells without killing normal cells both in vitro and in xenograft models. However, results from clinical trials of TRAIL-based therapy are disappointingly modest at best and many have demonstrated a lack of therapeutic benefit. Current research has focused on selecting a subpopulation of cancer patients who may benefit from TRAIL-based therapy and identifying best drugs to work with TRAIL. In the current study, we found that NSCLC cells with a KRAS mutation were highly sensitive to treatment with TRAIL and 5-fluorouracil (5FU). Compared with other chemotherapeutic agents, 5FU displayed the highest synergy with TRAIL in inducing apoptosis in mutant KRAS NSCLC cells. We also found that, on a mechanistic level, 5FU preferentially repressed survivin expression and induced expression of TRAIL death receptor 5 to sensitize NSCLC cells to TRAIL. The combination of low-dose 5FU and TRAIL strongly inhibited xenograft tumor growth in mice. Our results suggest that the combination of TRAIL and 5FU may be beneficial for patients with mutant KRAS NSCLC.

  9. Postoperative Radiotherapy in the Management of Resected Non-Small-Cell Lung Carcinoma: 10 Years' Experience in a Single Institute

    SciTech Connect

    Karakoyun-Celik, Omur; Yalman, Deniz; Bolukbasi, Yasemin; Cakan, Alpaslan; Cok, Gursel; Ozkok, Serdar

    2010-02-01

    Purpose: This study reports the long term outcomes of postoperative radiotherapy in patients with resection for non-small-cell lung cancer (NSCLC). Methods and Materials: A total of 98 patients with resected NSCLC who received postoperative radiotherapy (PORT) between January 1994 and December 2004 were retrospectively analyzed. The most frequently performed surgical procedure was lobectomy (59 patients), followed by pneumonectomy (25), wedge resection (8), and bilobectomy (6). Postoperative radiotherapy was delivered as an adjuvant treatment in 71 patients, after a wedge resection in 8 patients, and after an R1 resection in 19 patients. The PORT was administered using a Co-60 source in 86 patients and 6-MV photons in 12 patients. A Kaplan-Meier estimate of overall survival, locoregional control, and distant metastasis-free survival were calculated. Results: Stages included I (n =13), II (n = 50), IIIA (n = 29), and IIIB (n = 6). After a median follow-up of 52 months median survival was 61 months. The 5-year overall survival, locoregional control, and distant metastasis-free survival rates for the whole group were 50%, 78%, and 55% respectively. The RT dose, Karnofsky performance status, age, lateralization of the tumor, and pneumonectomy were independent prognostic factors for OAS; anemia and the number of involved lymph nodes were independent prognostic factors for LC. Conclusions: Doses of PORT of greater than 54 Gy were associated with higher death rate in patients with left-sided tumor, which may indicate a risk of radiation-induced cardiac mortality.

  10. Continuous infusion cisplatin and 5-fluorouracil with bolus vinorelbine in the treatment of advanced nonsmall cell carcinoma of the lung.

    PubMed

    Beuzeboc, P; Livartowski, A; Dierick, A; Paraiso, D; Pouillart, P

    1995-01-01

    Thirty-three patients, with histologically proven advanced nonsmall cell lung cancer (NSCLC) were treated at Institut Curie with a three-drug combination chemotherapy. The regimen consisted of cisplatin 25 mg/m2 per day continuous infusion (CI) and 5-fluorouracil (5-FU) CI 600 mg/m2 on 5 consecutive days with 30 minutes infusion navelbine 25 mg/m2 on days 1 and 5 only. Cycles were repeated every 28 days. Response was evaluated after three cycles. One patient died of an ischemic cerebrovascular stroke after the third cycle. Thirty-two pts were evaluable. Partial response was achieved in 11/20 patients with stage III disease (55%) and in 7/12 patients with stage IV disease (58%). WHO grade 4 toxicities were leucopenia 31%, thrombocytopenia 4%, and mucositis 4%. The tolerance was acceptable. Median survival was 19 months for stage III and 9.5 months for stage IV. We conclude that the combination of 5-FU, navelbine, and cisplatin is an effective chemotherapy regimen for patients with advanced stage NSCLC.

  11. Vascular endothelial growth factor is associated with neovascularization and influences progression of non-small cell lung carcinoma.

    PubMed

    Fontanini, G; Vignati, S; Boldrini, L; Chinè, S; Silvestri, V; Lucchi, M; Mussi, A; Angeletti, C A; Bevilacqua, G

    1997-06-01

    Vascular endothelial growth factor (VEGF) plays a pivotal role in the development of neovascularization in both physiological and pathological processes, e.g., developmental and reproductive angiogenesis, proliferative retinopathies, and cancers. Several solid tumors produce ample amounts of VEGF, which stimulates proliferation and migration of endothelial cells, thereby inducing neovascularization by a paracrine mechanism. Recently, VEGF expression has been shown to significantly affect the prognosis of different kinds of human cancer. Because neoangiogenesis represents an important prognostic indicator of poor prognosis in non-small cell lung cancer (NSCLC), we investigated the influence of VEGF during progression of this type of cancer and its relationship to tumoral neovascularization. VEGF expression was significantly associated with new vessel formation (r = 0.44; P < 0.0001). Moreover, in univariate analysis, VEGF expression significantly affected overall and disease-free survival (P = 0.00003 and P = 0. 0004, respectively). Backward stepwise regression analysis indicated that VEGF expression was an independent prognostic factor in patients with NSCLC. These findings support the hypothesis that VEGF is an important angiogenic factor in primary NSCLC and may help in predicting the outcome of this group of cancers.

  12. Fat quantification and analysis of lung transplant patients on unenhanced chest CT images based on standardized anatomic space

    NASA Astrophysics Data System (ADS)

    Tong, Yubing; Udupa, Jayaram K.; Torigian, Drew A.; Wu, Caiyun; Christie, Jason; Lederer, David J.

    2016-03-01

    Chest fat estimation is important for identifying high-risk lung transplant candidates. In this paper, an approach to chest fat quantification based on a recently formulated concept of standardized anatomic space (SAS) is presented. The goal of this paper is to seek answers to the following questions related to chest fat quantification on single slice versus whole volume CT, which have not been addressed in the literature. What level of correlation exists between total chest fat volume and fat areas measured on single abdominal and thigh slices? What is the anatomic location in the chest where maximal correlation of fat area with fat volume can be expected? Do the components of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) have the same area-to-volume correlative behavior or do they differ? The SAS approach includes two steps: calibration followed by transformation which will map the patient slice locations non-linearly to SAS. The optimal slice locations found for SAT and VAT based on SAS are different and at the mid-level of the T8 vertebral body for SAT and mid-level of the T7 vertebral body for VAT. Fat volume and area on optimal slices for SAT and VAT are correlated with Pearson correlation coefficients of 0.97 and 0.86, respectively. The correlation of chest fat volume with abdominal and thigh fat areas is weak to modest.

  13. Effects of targeted silencing of FOXC1 gene on proliferation and in vitro migration of human non-small-cell lung carcinoma cells

    PubMed Central

    Chen, Sumei; Jiao, Shunchang; Jia, Youchao; Li, Yang

    2016-01-01

    Background: The aim of this study was to evaluate the effects of targeted silencing of forkhead box C1 (FOXC1) gene with small interfering RNA (siRNA) on the proliferation and in vitro migration of human non-small-cell lung carcinoma (NSCLC) A549 and NCIH460 cells, and to explore the molecular mechanism. Methods: These cells were divided into FOXC1 siRNA groups and negative control groups. Results: Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) showed that compared with normal cells and paracancerous tissues, FOXC1 mRNA expressions in NSCLC cells and tissues were significantly higher (P<0.05). qRT-PCR and Western blot showed that FOXC1 siRNA effectively silenced FOXC1 gene expression in NSCLC cells. EdU labeling assay revealed that the proliferative capacity significantly decreased compared with that of normal control group after FOXC1 silencing (P<0.05). Significantly fewer cells in the transfected group migrated than those in negative control group did. After FOXC1 silencing, NSCLC cells were arrested in the G0/G1 phase, which were significantly different from those in negative control group (P<0.05). Compared with negative control group, the expression of cyclin D1 decreased and that of E-cadherin increased. Meanwhile, vimentin and MMP-2 expressions significantly reduced (P<0.05). FOXC1 siRNA effectively silenced FOXC1 gene expressions in NSCLC cells, inhibited their proliferation and invasion, and arrested them in the G0/G1 phase, suggesting that FOXC1 affected proliferation probably by regulating the expression of cell cycle-related protein cyclin D1. Conclusion: Silencing FOXC1 may evidently inhibit the migration of these cells by reversing the EMT process through suppressing cadherin, being associated with the expressions of extracellular MMPs. PMID:27648121

  14. Synergistic Effects between mTOR Complex 1/2 and Glycolysis Inhibitors in Non-Small-Cell Lung Carcinoma Cells.

    PubMed

    Jiang, Suhua; Zou, Zhengzhi; Nie, Peipei; Wen, Ruiling; Xiao, Yingying; Tang, Jun

    2015-01-01

    Cancer metabolism has greatly interested researchers. Mammalian target of rapamycin (mTOR) is dysregulated in a variety of cancers and considered to be an appealing therapeutic target. It has been proven that growth factor signal, mediated by mTOR complex 1 (mTORC1), drives cancer metabolism by regulating key enzymes in metabolic pathways. However, the role of mTORC2 in cancer metabolism has not been thoroughly investigated. In this study, by employing automated spectrophotometry, we found the level of glucose uptake was decreased in non-small-cell lung carcinoma (NSCLC) A549, PC-9 and SK-MES-1 cells treated with rapamycin or siRNA against Raptor, indicating that the inhibition of mTORC1 attenuated glycolytic metabolism in NSCLC cells. Moreover, the inhibition of AKT reduced glucose uptake in the cells as well, suggesting the involvement of AKT pathway in mTORC1 mediated glycolytic metabolism. Furthermore, our results showed a significant decrease in glucose uptake in rictor down-regulated NSCLC cells, implying a critical role of mTORC2 in NSCLC cell glycolysis. In addition, the experiments for MTT, ATP, and clonogenic assays demonstrated a reduction in cell proliferation, cell viability, and colony forming ability in mTOR inhibiting NSCLC cells. Interestingly, the combined application of mTORC1/2 inhibitors and glycolysis inhibitor not only suppressed the cell proliferation and colony formation, but also induced cell apoptosis, and such an effect of the combined application was stronger than that caused by mTORC1/2 inhibitors alone. In conclusion, this study reports a novel effect of mTORC2 on NSCLC cell metabolism, and reveals the synergistic effects between mTOR complex 1/2 and glycolysis inhibitors, suggesting that the combined application of mTORC1/2 and glycolysis inhibitors may be a new promising approach to treat NSCLC.

  15. Comparative efficacy of whole-brain radiotherapy with and without elemene liposomes in patients with multiple brain metastases from non-small-cell lung carcinoma

    PubMed Central

    Sun, Y.N.; Zhang, Z.Y.; Zeng, Y.C.; Chi, F.; Jin, X.Y.; Wu, R.

    2016-01-01

    Purpose We explored and compared the clinical effects of whole-brain radiotherapy (wbrt) with and without elemene liposomes in patients with multiple brain metastases from non-small-cell lung carcinoma (nsclc). Methods We retrospectively analyzed 62 patients with multiple brain metastases from nsclc who received wbrt (30 Gy in 10 fractions) at Shengjing Hospital of China Medical University from January 2012 to May 2013. In 30 patients, elemene liposomes (400 mg) were injected intravenously via a peripherally inserted central catheter for 21 consecutive days from the first day of radiotherapy. Overall survival (os) and nervous system progression-free survival (npfs) for the two groups were compared by Kaplan–Meier analysis. Factors influencing npfs were examined by Cox regression analysis. Chi-square or Fisher exact tests were used for group comparisons. Results The median os was 9.0 months in the wbrt plus elemene group and 7.8 months in the wbrt-alone group (p = 0.581); the equivalent median npfs durations were 5.2 months and 3.7 months (p = 0.005). Patient treatment plan was an independent factor associated with npfs (p = 0.002). Tumour response and disease-control rates in the wbrt plus elemene group were 26.67% and 76.67% respectively; they were 18.75% and 62.5% in the wbrt group (p = 0.452). Compared with the patients in the wbrt-alone group, significantly fewer patients in the wbrt plus elemene group developed headaches (p = 0.04); quality of life was also significantly higher in the wbrt plus elemene group both at 1 month and at 2 months (p = 0.021 and p = 0.001 respectively). Conclusions The addition of elemene liposomes to wbrt might prolong npfs in patients with multiple brain metastases from nsclc, while also reducing the incidence of headache and improving patient quality of life. PMID:27536187

  16. Plasma level of metastasis-associated lung adenocarcinoma transcript 1 is associated with liver damage and predicts development of hepatocellular carcinoma.

    PubMed

    Konishi, Hirotaka; Ichikawa, Daisuke; Yamamoto, Yusuke; Arita, Tomohiro; Shoda, Katsutoshi; Hiramoto, Hidekazu; Hamada, Junichi; Itoh, Hiroshi; Fujita, Yuji; Komatsu, Shuhei; Shiozaki, Atsushi; Ikoma, Hisashi; Ochiai, Toshiya; Otsuji, Eigo

    2016-02-01

    Recent studies have shown that metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was overexpressed in many human solid cancers, however, its roles in plasma of hepatocellular carcinoma (HCC) patients were unclear. The aim of this study was to investigate the significance of plasma MALAT1 levels in HCC patients. Plasma samples were collected from pre-operative HCC, hepatic disease patients, and healthy controls, and tissue samples from HCC patients and colorectal cancer patients with liver metastasis. Plasma and tissue MALAT1 levels were measured. Plasma MALAT1 levels were progressively and significantly higher in HCC patients than hepatic disease patients, and higher in hepatic disease patients than healthy controls. The expression of MALAT1 in HCC tissue was slightly higher than that in paired non-cancerous liver tissue, but not significant. The expression of MALAT1 in the non-cancerous liver tissue of 20 HCC patients was significantly higher than that in normal liver tissue of 13 colorectal cancer patients. In contrast, plasma MALAT1 levels were significantly low in HCC patients with hepatitis B infection, and significantly high in patients with liver damage B or liver cirrhosis. In a receiver-operator curve analysis of HCC and hepatic disease patients, the cut-off value of plasma MALAT1 was 1.60 and the area under the curve was 0.66. Plasma MALAT1 levels were not correlated with α-fetoprotein or protein induced by vitamin K absence II, whereas sensitivity and specificity for the detection of HCC with the combination of MALAT1, α-fetoprotein, and protein induced by vitamin K absence II were 88.6% and 75%, respectively. In conclusion, the plasma MALAT1 level is associated with liver damage, and has clinical utility for predicting development of HCC.

  17. Aggressive Therapy for Patients with Non-small Cell Lung Carcinoma and Synchronous Brain-only Oligometastatic Disease is Associated with Long-term Survival

    PubMed Central

    Gray, Phillip J.; Mak, Raymond H.; Yeap, Beow Y.; Cryer, Sarah K.; Pinnell, Nancy E.; Christianson, Laura W.; Sher, David J.; Arvold, Nils D.; Baldini, Elizabeth H.; Chen, Aileen B.; Kozono, David E.; Swanson, Scott J.; Jackman, David M.; Alexander, Brian M.

    2015-01-01

    Objectives Optimal therapy for patients with non-small cell lung carcinoma (NSCLC) presenting with synchronous brain-only oligometastases (SBO) is not well defined. We sought to analyze the effect of differing therapeutic paradigms in this subpopulation. Materials and Methods We retrospectively analyzed NSCLC patients with 1-4 SBO diagnosed between 1/2000 and 1/2011 at our institution. Patients with T0 tumors or documented Karnofsky Performance Status <70 were excluded. Aggressive thoracic therapy (ATT) was defined as resection of the primary disease or chemoradiotherapy whose total radiation dose exceeded 45 Gy. Cox proportional hazards and competing risks models were used to analyze factors affecting survival and first recurrence in the brain. Results Sixty-six patients were included. Median follow-up was 31.9 months. Intrathoracic disease extent included 9 stage I, 10 stage II and 47 stage III patients. Thirty-eight patients received ATT, 28 did not. Patients receiving ATT were younger (median age 55 vs. 60.5 years, p=0.027) but were otherwise similar to those who did not. Receipt of ATT was associated with prolonged median overall survival (OS) (26.4 vs. 10.5 months; p<0.001) with actuarial 2-year rates of 54% vs. 26%. ATT remained associated with OS after controlling for age, thoracic stage, performance status and initial brain therapy (HR 0.40, p=0.009). On multivariate analysis, the risk of first failure in the brain was associated with receipt of ATT (HR 3.62, p=0.032) and initial combined modality brain therapy (HR 0.34, p=0.046). Conclusion Aggressive management of thoracic disease in NSCLC patients with SBO is associated with improved survival. Careful management of brain disease remains important, especially for those treated aggressively. PMID:24974152

  18. Randomized trial of radiotherapy to the thorax in limited small-cell carcinoma of the lung treated with multiagent chemotherapy and elective brain irradiation: a preliminary report

    SciTech Connect

    Perez, C.A.; Einhorn, L.; Oldham, R.K.; Greco, F.A.; Cohen, H.J.; Silberman, H.; Krauss, S.; Hornback, N.; Comas, F.; Omura, G.

    1984-11-01

    A total of 304 patients with limited small-cell carcinoma of the lung were treated with a combination of cyclophosphamide, Adriamycin, and vincristine (CAV) and elective brain irradiation (3,600 rad TD in 14 fractions). The patients were randomized to either receive or not receive thoracic irradiation (4000 rad TD, split course). Of the 304 patients, 291 were eligible for the study. Two hundred eighteen (75%) were completely evaluable. In each group, 81% of the patients had a Karnofsky index of 80% or higher and 14% had supraclavicular or scalene lymph nodes. Patients treated with CAV and no thoracic irradiation had a complete response (CR) of 48%, in contrast to 63% for those receiving chest irradiation. In the first group, the complete and partial response rate was 70%; in the second, 80%. The median survival for the eligible patients treated with CAV and brain radiation therapy was 49 weeks; for those treated with the same regimen plus thoracic irradiation, the median survival was 60 weeks. The actuarial two-year tumor-free survival is 19% in the first group and 28% in the second group. The median survival for the responders in the CAV plus brain irradiation group was 57 weeks and for those receiving thoracic irradiation, 78 weeks. Thoracic failure was 52% in patients not treated with thoracic radiation therapy v 36% in those receiving it (P . .06). The distant metastases incidence was 23% in patients not treated with thoracic radiation and 35% in patients treated with thoracic radiation. Hematologic toxicity was comparable in both groups; 30% of the patients had moderate to severe granulocytopenia and 6%, low homoglobin. Two toxicity-related deaths occurred (one in each group). Moderate gastrointestinal toxicity was noted in 41% and severe in 16% of the patients receiving CAV and brain irradiation without thoracic radiotherapy v 44% and 20% in those irradiated in the thorax.

  19. Chemical constituents and anticancer activity of Curcuma zedoaria roscoe essential oil against non-small cell lung carcinoma cells in vitro and in vivo.

    PubMed

    Chen, Chien-chang; Chen, Yuhsin; Hsi, Yi-Ting; Chang, Chih-Sheng; Huang, Li-Fen; Ho, Chi-Tang; Way, Tzong-Der; Kao, Jung-Yie

    2013-11-27

    In this study, we report that the essential oil obtained from Curcuma zedoaria Roscoe, known as zedoary, possesses efficient cytotoxic effects on non-small cell lung carcinoma (NSCLC) cells and causes cell apoptosis. Zedoary essential oil increased the sub-G1 population and the level of annexin-V binding and induced cleavage and activation of caspase-3, -8, and -9 and poly(ADP ribose) polymerase. Decreases in the levels of Bcl-2 and Bcl-xL and an increase in the Bax/Bcl-2 ratio were also observed following zedoary essential oil treatment. Notably, zedoary essential oil led to the release of AIF, endonuclease G, and cytochrome c into the cytosol and increased levels of p53 in H1299 cells. Our results indicate that zedoary essential oil slightly inhibited the phosphorylation of ERK1/2 and enhanced the phosphorylation of JNK1/2 and p38. Zedoary essential oil also inhibited AKT/NF-κB signaling pathways in H1299 cells. Moreover, intraperitoneal administration of zedoary essential oil significantly suppressed the growth of H1299 cells in vivo. In addition, potential active compounds were detected using gas chromatography and mass spectrometry. 8,9-Dehydro-9-formyl-cycloisolongifolene, 6-ethenyl-4,5,6,7-tetrahydro-3,6-dimethyl-5-isopropenyl-trans-benzofuran, eucalyptol, and γ-elemene were found in zedoary essential oil. In summary, our findings provide insight into the molecular mechanisms underlying zedoary essential oil-induced apoptosis in NSCLC cells that are worthy of further study.

  20. Synergistic suppression of microtubule dynamics by discodermolide and paclitaxel in non-small cell lung carcinoma cells.

    PubMed

    Honore, Stéphane; Kamath, Kathy; Braguer, Diane; Horwitz, Susan Band; Wilson, Leslie; Briand, Claudette; Jordan, Mary Ann

    2004-07-15

    Discodermolide is a new microtubule-targeted antimitotic drug in Phase I clinical trials that, like paclitaxel, stabilizes microtubule dynamics and enhances microtubule polymer mass in vitro and in cells. Despite their apparently similar binding sites on microtubules, discodermolide acts synergistically with paclitaxel to inhibit proliferation of A549 human lung cancer cells (L. Martello et al., Clin. Cancer Res., 6: 1978-1987, 2000). To understand their synergy, we examined the effects of the two drugs singly and in combination in A549 cells and found that, surprisingly, their antiproliferative synergy is related to their ability to synergistically inhibit microtubule dynamic instability and mitosis. The combination of discodermolide and paclitaxel at their antiproliferative IC(50)s (7 nm for discodermolide and 2 nm for paclitaxel) altered all of the parameters of dynamic instability synergistically except the time-based rescue frequency. For example, together the drugs inhibited overall microtubule dynamicity by 71%, but each drug individually inhibited dynamicity by only 24%, giving a combination index (CI) of 0.23. Discodermolide and paclitaxel also synergistically blocked cell cycle progression at G(2)-M (41, 9.6, and 16% for both drugs together, for discodermolide alone, and for paclitaxel alone, respectively; CI = 0.59), and they synergistically enhanced apoptosis (CI = 0.85). Microtubules are unique receptors for drugs. The results suggest that ligands that bind to large numbers of binding sites on an individual microtubule can interact in a poorly understood manner to synergistically suppress microtubule dynamic instability and inhibit both mitosis and cell proliferation, with important consequences for combination clinical therapy with microtubule-targeted drugs.

  1. Myricanol induces apoptotic cell death and anti-tumor activity in non-small cell lung carcinoma in vivo.

    PubMed

    Dai, Guanhai; Tong, Yeling; Chen, Xuan; Ren, Zeming; Ying, Xuhua; Yang, Feng; Chai, Kequn

    2015-01-01

    This study explored the inhibiting effect and mechanism of myricanol on lung adenocarcinoma A549 xenografts in nude mice. Forty nude mice with subcutaneous A549 xenografts were randomly divided into five groups: high-dose myricanol (40 mg/kg body weight) group; middle-dose myricanol (20 mg/kg body weight) group; low-dose myricanol (10 mg/kg body weight) group; polyethylene glycol 400 vehicle group (1 mL/kg); and tumor model group. Nude mice were sacrificed after 14 days of treatment and the tumor inhibition rate (TIR, %) was then calculated. The relative mRNA expression levels of Bax, Bcl-2, VEGF, HIF-1α, and survivin in the tumor tissues were determined by real-time PCR. TUNEL assay was applied to determine cellular apoptosis, while IHC test was performed to detect the protein expression levels of Bax, Bcl-2, VEGF, HIF-1α, and survivin. The TIR of the three myricanol-treated groups ranged from 14.9% to 38.5%. The IHC results showed that the protein expression of Bcl-2, VEGF, HIF-1α, and survivin were consistently downregulated, whereas that of Bax was upregulated after myricanol treatment. Myricanol also significantly upregulated the mRNA expression of Bax and downregulated that of Bcl-2, VEGF, HIF-1α, and survivin in a dose-dependent manner (p < 0.05 to 0.001). These results are consistent with those of IHC. The TUNEL assay results indicated that apoptotic-positive cells significantly increased in the myricanol-treated tumor tissues compared with the cells of the vehicle control group (p < 0.01 to 0.001). These data suggest that myricanol could significantly decelerate tumor growth in vivo by inducing apoptosis. PMID:25629230

  2. Effect of Ganoderma on drug-sensitive and multidrug-resistant small-cell lung carcinoma cells.

    PubMed

    Sadava, David; Still, David W; Mudry, Ryan R; Kane, Susan E

    2009-05-18

    Multidrug resistance is a major problem in small-cell lung cancer (SCLC). Ganoderma lucidum is a widely used herb in traditional Chinese medicine. We tested the effects of Ganoderma on drug-sensitive (H69) and multi-drug resistant (VPA) human SCLC cells. Both cells showed equal cytotoxicity when incubated with extracts of mycelia of 9 species of Ganoderma, including G. lucidum. Cells treated with the IC(50) of cytotoxic Ganoderma and analyzed by flow cytometry-PI staining showed increases in S phase. When compared untreated controls or SCLC cells treated with extracts of non-cytotoxic Ganoderma species, cells treated with extracts of cytotoxic Ganoderma species responded with an induction of apoptosis similar to cells treated with the chemotherapeutic drugs etoposide and doxorubicin. This was shown by four criteria: increased DNA fragmentation within cells as measured by ELISA; increased TUNEL staining for DNA breaks; increased specific activities of caspases 3 and 9, but not caspase 8 by colorimetric assays, indicating the endogenous pathway; and similar patterns changes in the expressions of 9 genes involved in the cell cycle/apoptosis, as measured by RT-PCR and capillary electrophoresis. Pre-incubation of drug-resistant SCLC cells with cytotoxic Ganoderma reduced the IC(50) for etoposide (3.4-0.21 microM) and doxorubicin (0.19-0.04 microM). These results show that extracts of several species of Ganoderma are cytotoxic to both drug-sensitive and drug-resistant SCLC cells, are pro-apoptotic, induce gene expression patterns that are similar to SCLC cells treated with chemotherapeutic drugs, and can reverse resistance to chemotherapeutic drugs.

  3. 18FDG PET-CT standardized uptake value for the prediction of radiation pneumonitis in patients with lung cancer receiving radiotherapy

    PubMed Central

    ZHANG, YONG; YU, YONGHUA; YU, JINMING; FU, ZHENG; LIU, TONGHAI; GUO, SHOUFANG

    2015-01-01

    The present study aimed to determine if the standardized uptake value (SUV) determined with 18F-FDG PET-CT can be used to predict radiation pneumonitis (RP) in lung cancer patients who receive radiotherapy. A total of 40 patients with non-small cell lung cancer received 18F-FDG PET-CT examinations prior to and following radiotherapy. The average SUV of lung tissue prior to and following radiation were measured at differing radiation doses. SUV differences between patients with and without RP, and the SUV ratio of the irradiated lung tissues compared with that of non-irradiated lung tissues (L/B) were compared. There were no differences in the mean SUV between the RP and no RP groups prior to radiotherapy. There were also no significant differences in the mean SUV of lung tissue within groups or between the no RP and RP groups with radiation doses of <5 Gy, 5 to ≤14.9 Gy and 15 to ≤34.9 Gy (all P>0.05) following radiotherapy. There were, however, statistically significant differences in the mean SUV of lung tissue within groups or between the no RP and RP groups with doses of ≥60 Gy prior to therapy and 35 to ≤59.9 Gy and ≥60 Gy following therapy (all P<0.05). When the L/B ratio was ≥3, the incidence of RP was 50%, and when the L/B ratio was ≥2.5 the incidence was 40.7%. When the L/B ratio was <2, there were no cases of RP. In conclusion, the present study indicates that 18F-FDG PET-CT can be used to predict RP by L/B ratio. PMID:26722262

  4. Epidemiology of Lung Cancer in Korea: Recent Trends

    PubMed Central

    Park, Ji Young

    2016-01-01

    Lung cancer causes the most cancer deaths in Korea. Although the smoking rate has begun to decrease, the prevalence of lung cancer is still increasing. We reviewed the national lung cancer registry data and the data published about lung cancer in Korea. In 2012, the crude incidence rate of lung cancer was 43.9 per 100,000. The age-standardized mortality rate of lung cancer was 19.8 per 100,000. The 5-year relative survival rate for lung cancer was 11.3% from 1993 to 1995 and increased to 21.9% in the period from 2008 to 2012. Lung cancer occurring in never-smokers was estimated to increase in Korea. Adenocarcinoma is steadily increasing in both women and men and has replaced squamous cell carcinoma as the most common type of lung cancer in Korea. In patients with adenocarcinoma, the frequency of EGFR mutations was 43% (range, 20%–56%), while that of the EMK4-ALK gene was less than 5%. PMID:27064578

  5. Somatostatin and dopamine receptor expression in lung carcinoma cells and effects of chimeric somatostatin-dopamine molecules on cell proliferation.

    PubMed

    Ferone, Diego; Arvigo, Marica; Semino, Claudia; Jaquet, Philippe; Saveanu, Alexandru; Taylor, John E; Moreau, Jacques-Pierre; Culler, Michael D; Albertelli, Manuela; Minuto, Francesco; Barreca, Antonina

    2005-12-01

    To study somatostatin/dopamine (SS/D) synergy in a human cell system constitutively expressing SS and D receptors (SSR and DR, respectively), we characterized the expression of SSR and DR subtypes in the non-small-cell lung cancer line Calu-6, and then we evaluated the effect on cell proliferation of SS/D chimeric molecules (BIM-23A387 and BIM-23A370), which bind with high affinity both sst(2) and D(2)R, and compared the results with those obtained by using SS-14 and subtype-selective SS analogs (SSA) and D agonists (DA). Because Calu-6 cells produce insulin-like growth factor (IGF) and IGF-binding protein (IGFBP) peptides, which play a role in the autocrine/paracrine control of cell growth, we also investigated the effects of chimeric compounds on secretion and expression of IGF system components. Relative high levels of sst(2) and the long isoform of the D(2)R were detected by real-time RT-PCR and Western blot in Calu-6, together with sst(5) and to a lesser extent sst(3) and D(4)R. BIM-23A387 and BIM-23A370 significantly inhibited growth of Calu-6, whereas IGF-IGFBP secretion or expression was unaffected, suggesting a direct inhibitory effect. The inhibition of cell growth, measured by both [(3)H]thymidine incorporation and cell count, was significantly lower when individual SSA and DA control peptides or subtype-specific SSA and DA were tested. BIM-23A370 was more potent than BIM-23A387 (P < 0.001). These findings show that SS/D chimeras can inhibit Calu-6 proliferation in an IGF-independent manner and suggest that this enhanced potency might be because of the induction of SSR/DR dimerization. The Calu-6 cell line, constitutively expressing SSR and DR, provides a suitable model to elucidate the mechanism of action of SSA and DA on regulation of cell growth and to characterize the interaction between SSR and DR.

  6. High-titer collapsin response-mediating protein-associated (CRMP-5) paraneoplastic optic neuropathy and Vitritis as the only clinical manifestations in a patient with small cell lung carcinoma.

    PubMed

    Margolin, Edward; Flint, Andrew; Trobe, Jonathan D

    2008-03-01

    Paraneoplastic optic neuropathy (PON) is a rare syndrome usually associated with small cell lung carcinoma. In the 27 rigorously reported cases, neurologic manifestations other than visual loss have been present in all but 2. In the single case in which vision improved in response to treatment of the cancer, the collapsin response-mediating protein (CRMP)-5 titer did not change, and the ophthalmic examination was not detailed. We describe a patient with optic neuropathy and vitritis as the only clinical manifestations of PON marked by an extremely high titer of CRMP-5 antibody. Treatment of the underlying small cell lung cancer coincided with resolution of the visual abnormalities and a dramatic decrease in the CRMP-5 titer.

  7. Clinical efficacy and toxicity of standard dose adriamycin in hyperbilirubinaemic patients with hepatocellular carcinoma: relation to liver tests and pharmacokinetic parameters.

    PubMed Central

    Johnson, P. J.; Dobbs, N.; Kalayci, C.; Aldous, M. C.; Harper, P.; Metivier, E. M.; Williams, R.

    1992-01-01

    A standard dose of Adriamycin (60 mg m-2) was administered to 30 patients with inoperable hepatocellular carcinoma, 16 of whom were hyperbilirubinaemic (18-37 mumol l-1). The hyperbilirubinaemic patients experienced marked myelosuppression, but only minor symptomatic side-effects. The degree of neutropenia was directly related to the serum bilirubin concentration, but not to any other standard liver test, presence or absence of cirrhosis, or any pharmacokinetic parameter studied including the area under the Adriamycin or adriamycinol concentration-time curve to 48 h or infinity, or the terminal half-life of Adriamycin. The area under the log concentration-time curve was significantly greater for both Adriamycin and adriamycinol in patients who were hyperbilirubinaemic compared to those with normal bilirubin. Whilst hyperbilirubinaemic patients may tolerate a full dose of Adriamycin, we found no evidence that this was associated with a better response rate, which was disappointingly low at only 18%. PMID:1316777

  8. Testing lung cancer drugs and therapies in mice

    Cancer.gov

    National Cancer Institute (NCI) investigators have designed a genetically engineered mouse for use in the study of human lung squamous cell carcinoma (SCC). SCC is a type of non-small cell lung carcinoma, one of the most common types of lung cancer, with

  9. Lung cancer: Current status and prospects for the future

    SciTech Connect

    Mountain, C.F.; Carr, D.T.

    1986-01-01

    This book contains 32 papers. Some of the titles are: Activation of cellular ras genes in human neoplasms; The valve of definitive radiation therapy of unresectable squamous cell carcinoma, large cell carcinoma, and adenocarcinoma of the lung; Current concepts of chemotherapy and radiotherapy for small cell lung cancer, and Current status of immunotherapy for lung cancer.

  10. Thoracic and elective brain irradiation with concomitant or delayed multiagent chemotherapy in the treatment of localized small cell carcinoma of the lung: a randomized prospective study by the Southeastern Cancer Study Group. [X-ray

    SciTech Connect

    Perez, C.A.; Krauss, S.; Bartolucci, A.A.; Durant, J.R.; Lowenbraun, S.; Salter, M.M.; Storaasli, J.; Kellermeyer, R.; Comas, F.

    1981-05-15

    A prospective randomized study was carried out to compare the effectiveness of concomitant or delayed multiagent chemotherapy combined with irradiation to the primary tumor and regional lymph nodes and to the brain in a group of 70 patients with histologically proven small cell undifferentiated carcinoma of the lung. Complete and partial response in both groups was comparable, and the overall survival was comparable. However, relapse-free survival was significantly higher in patients receiving concomitant chemotherapy and irradiation in comparison with the radiotherapy alone group. Disease-free survival was higher in the concomitant chemotherapy-radiotherapy patients, although survival was not significantly modified, probably because of suboptimal chemotherapy. The incidence of distant metastasis was slightly lower in the chemotherapy groups. Brain metastases were noted in 7% of the patients in both groups. Increased intrathoracic recurrences were noted in patients with lower doses of irradiation. The study emphasizes the need for intensive chemotherapy and adequate radiation therapy to improve survival of patients with small cell undifferentiated carcinoma of the lung.

  11. Combination chemotherapy-radiotherapy with and without the methanol-extraction residue of bacillus Calmette-Guerin (MER) in small cell carcinoma of the lung: a prospective randomized trial of the Piedmont Oncology Association

    SciTech Connect

    Jackson, D.V.; Paschal, B.R.; Ferree, C.

    1982-07-01

    The effect of addition of the nonspecific immunostimulant, MER, to combined treatment with chemotherapy and radiotherapy in small cell carcinoma of the lung was evaluated in a prospective randomized trial involving 102 evaluable patients. Chemotherapy consisted of cyclophosphamide, Adriamycin, vincristine, methotrexate, and CCNU; and radiotherapy was administered to the primary lesion, mediastinum, supraclavicular areas, and whole brain. Of 47 patients administered MER 400 mcg intradermally every six weeks, 12 (26%) attained complete remission with a median survival of 22.9 months. Complete remission was observed in 17 (31%) of 55 patients who received no MER with a median survival of 20.0 months (p > 0.05). Survival greater than or equal to 2 years has been observed in five patients who received MER and two patients who did not receive MER. The response rate and duration, survival, and toxicity of the two treatment arms were similar with the exception of cutaneous and occasional systemic reaction to MER. MER as used in this study has not influenced the overall results of a combined modality treatment program for patients with small cell carcinoma of the lung.

  12. The Impact of Local and Regional Disease Extent on Overall Survival in Patients With Advanced Stage IIIB/IV Non-Small Cell Lung Carcinoma

    SciTech Connect

    Higginson, Daniel S.; Chen, Ronald C.; Tracton, Gregg; Morris, David E.; Halle, Jan; Rosenman, Julian G.; Stefanescu, Mihaela; Pham, Erica; Socinski, Mark A.; Marks, Lawrence B.

    2012-11-01

    Purpose: Patients with advanced stage IIIB or stage IV non-small cell lung carcinoma are typically treated with initial platinum-based chemotherapy. A variety of factors (eg, performance status, gender, age, histology, weight loss, and smoking history) are generally accepted as predictors of overall survival. Because uncontrolled pulmonary disease constitutes a major cause of death in these patients, we hypothesized that clinical and radiographic factors related to intrathoracic disease at diagnosis may be prognostically significant in addition to conventional factors. The results have implications regarding the selection of patients for whom palliative thoracic radiation therapy may be of most benefit. Methods and Materials: We conducted a pooled analysis of 189 patients enrolled at a single institution into 9 prospective phase II and III clinical trials involving first-line, platinum-based chemotherapy. Baseline clinical and radiographic characteristics before trial enrollment were analyzed as possible predictors for subsequent overall survival. To assess the relationship between anatomic location and volume of disease within the thorax and its effect on survival, the pre-enrollment computed tomography images were also analyzed by contouring central and peripheral intrapulmonary disease. Results: On univariate survival analysis, multiple pulmonary-related factors were significantly associated with worse overall survival, including pulmonary symptoms at presentation (P=.0046), total volume of intrathoracic disease (P=.0006), and evidence of obstruction of major bronchi or vessels on prechemotherapy computed tomography (P<.0001). When partitioned into central and peripheral volumes, central (P<.0001) but not peripheral (P=.74) disease was associated with worse survival. On multivariate analysis with known factors, pulmonary symptoms (hazard ratio, 1.46; P=.042), central disease volume (hazard ratio, 1.47; P=.042), and bronchial/vascular compression (hazard ratio, 1

  13. Thrombospondins I and II messenger RNA expression in lung carcinoma: relationship with p53 alterations, angiogenic growth factors, and vascular density.

    PubMed

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

    1999-01-01

    Thrombospondin (TSP) is a Mr 450,000 multifunctional matrix glycoprotein that interferes with tumor growth, angiogenesis, and metastasis. It has recently been shown that TSP expression is enhanced by the product of the p53 gene and that a down-regulation of TSP may be observed when alterations of the p53 protein occur. Moreover, a number of studies have demonstrated a regulatory activity of p53 on human vascular endothelial growth factor (VEGF), although additional investigations will be necessary to understand their relationship. In non-small cell lung carcinoma (NSCLC), neoangiogenesis, p53 alterations, and VEGF expression seem to have meaningful implications in the development and progression of this type of cancer. The aim of this study is to identify and quantitate TSP I and TSP II mRNA in NSCLCs with respect to p53 alterations, angiogenic growth factor expression, and microvascular density. A series of 24 cases of NSCLC were analyzed. Eleven of 24 of the cases were positive for TSP II mRNA, whereas 8 of 24 showed TSP I mRNA expression. A significant inverse association was found between TSP I mRNA and fibroblast growth factor (FGF) protein expression (P = 0.00001). Tumors with low FGF protein expression (< or = 40% of positive cells) presented a number of TSP I cDNA molecules, significantly higher than tumors expressing high levels of FGF protein. No association was found between TSP mRNA expression and other angiogenic growth factors (i.e., VEGF) or tumoral neovascularization. On the contrary, tumors with high levels of FGF showed a higher number of microvessels (P = 0.05). By PCR-single-strand conformational polymorphism analysis, we observed aberrations of the p53 gene in 19 of the 24 tumor samples. No association was found between p53 alterations and TSP mRNA expression. Instead, an interestingly significant association was found between the presence of p53 mutations and high VEGF protein expression (P = 0.01) and neovascularization (P = 0.03). Highly

  14. [Grading of lung cancer].

    PubMed

    Bohle, R M; Schnabel, P A

    2016-07-01

    In comparison with other tumor entities there is no common generally accepted grading system for lung cancer with clearly defined criteria and clinical relevance. In the recent fourth edition of the World Health Organization (WHO) classification from 2015 of tumors of the lungs, pleura, thymus and heart, there is no generally applicable grading for pulmonary adenocarcinomas, squamous cell carcinomas or rarer forms of carcinoma. Since the new IASLC/ATS/ERS classification of adenocarcinomas published in 2011, 5 different subtypes with significantly different prognosis are proposed. This results in an architectural (histologic) grading, which is usually applied to resection specimens. For squamous cell carcinoma the number of different histological subtypes in the new WHO classification was reduced compared to earlier versions but without a common grading system. In recent publications nesting and budding were proposed as the main (histologic) criteria for a grading of squamous cell carcinomas. The grading of neuroendocrine tumors (NET) of the lungs in comparison with NET in other organs is presented in a separate article in this issue. Certain rare tumor types are high grade per definition: small cell, large cell and pleomorphic carcinomas, carcinosarcomas and pulmonary blastomas. In the future it is to be expected that these developments will be further refined, e. g. by adding further subtypes for adenocarcinomas and cytologic and/or nuclear criteria for adenocarcinoma and/or squamous cell carcinomas. PMID:27356985

  15. Recombinant Interleukin-15 in Treating Patients With Advanced Melanoma, Kidney Cancer, Non-small Cell Lung Cancer, or Squamous Cell Head and Neck Cancer

    ClinicalTrials.gov

    2016-05-05

    Head and Neck Squamous Cell Carcinoma; Recurrent Head and Neck Carcinoma; Recurrent Non-Small Cell Lung Carcinoma; Recurrent Renal Cell Carcinoma; Recurrent Skin Carcinoma; Stage III Renal Cell Cancer; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIA Skin Melanoma; Stage IIIB Non-Small Cell Lung Cancer; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Non-Small Cell Lung Cancer; Stage IV Renal Cell Cancer; Stage IV Skin Melanoma

  16. Cixutumumab, Everolimus, and Octreotide Acetate in Treating Patients With Advanced Low to Intermediate Grade Neuroendocrine Carcinoma

    ClinicalTrials.gov

    2016-07-14

    Gastrin-Producing Neuroendocrine Tumor; Lung Carcinoid Tumor; Metastatic Digestive System Neuroendocrine Tumor G1; Pancreatic Glucagonoma; Pancreatic Insulinoma; Pancreatic Polypeptide Tumor; Paraganglioma; Recurrent Digestive System Neuroendocrine Tumor G1; Recurrent Merkel Cell Carcinoma; Recurrent Pancreatic Neuroendocrine Carcinoma; Regional Digestive System Neuroendocrine Tumor G1; Somatostatin-Producing Neuroendocrine Tumor; Stage III Merkel Cell Carcinoma; Stage IV Merkel Cell Carcinoma; Thyroid Gland Medullary Carcinoma

  17. RRx-001 in Refractory Small-Cell Lung Carcinoma: A Case Report of a Partial Response after a Third Reintroduction of Platinum Doublets

    PubMed Central

    Carter, Corey A.; Oronsky, Bryan T.; Caroen, Scott Z.; Scicinski, Jan J.; Degesys, Aiste; Kim, Michelle M.; Oronsky, Arnold L.; Lybeck, Harry; Cabrales, Pedro; Oronsky, Neil; Reid, Tony; Roswarski, Joseph; Brzezniak, Christina

    2016-01-01

    RRx-001 is a pan-active, systemically nontoxic epigenetic inhibitor under investigation in advanced non-small cell lung cancer, small-cell lung cancer and high-grade neuroendocrine tumors in a Phase II clinical trial entitled TRIPLE THREAT (NCT02489903), which reexposes patients to previously effective but refractory platinum doublets after treatment with RRx-001. The purpose of this case study is first to report a partial response to carboplatin and etoposide in a patient with small-cell lung cancer pretreated with RRx-001, indicating episensitization or resensitization by epigenetic mechanisms, and second to discuss the literature related to small-cell lung cancer and episensitization. PMID:27065849

  18. [Lung cancer in elderly patients: lung cancer and lung function].

    PubMed

    Tanita, Tatsuo

    2005-07-01

    The incidence of bronchogenic carcinoma is increasing as life expectancy rises. With increase in the aged population in Japan, the number of patients suffering from lung cancer and candidates for lung resections are increasing. In this paper, the author lists up indispensable procedures for diagnosis, namely, lung function tests, unilateral pulmonary arterial occlusion test and exercise tolerance test. The cut-offs for identifying candidates for elderly patients for lung resections can be applied the same cut-offs for younger patients. Also the author indicates the importance of postoperative management for lung lobe resections. In order to prevent postoperative problems such as congestive heart failure that might be a fetal complication, the most useful check values after the lung surgery for elderly patients are rate of transfusion and urine volume. In conclusion, when elderly patients assert their rights to undergo lung surgery, we, the thoracic surgeons, should reply their requests under the equal quality of safe surgery as that for younger patients. Besides, it is desirable that even elderly patients, over 80 years old, who undergo lung surgery should guarantee their quality of daily life after surgery.

  19. Telomere length and the risk of lung cancer.

    PubMed

    Jang, Jin Sung; Choi, Yi Young; Lee, Won Kee; Choi, Jin Eun; Cha, Sung Ick; Kim, Yeon Jae; Kim, Chang Ho; Kam, Sin; Jung, Tae Hoon; Park, Jae Yong

    2008-07-01

    Telomeres play a key role in the maintenance of chromosome integrity and stability. There is growing evidence that short telomeres induce chromosome instability and thereby promote the development of cancer. We investigated the association of telomere length and the risk of lung cancer. Relative telomere length in peripheral blood lymphocytes was measured by quantitative polymerase chain reaction in 243 lung cancer patients and 243 healthy controls that were frequency-matched for age, sex and smoking status. Telomere length was significantly shorter in lung cancer patients than in controls (mean +/- standard deviation: 1.59 +/- 0.75 versus 2.16 +/- 1.10, P < 0.0001). When the subjects were categorized into quartiles based on telomere length, the risk of lung cancer was found to increase as telomere length shortened (P(trend) < 0.0001). In addition, when the median of telomere length was used as the cutoff between long and short telomeres, individuals with short telomeres were at a significantly higher risk of lung cancer than those with long telomeres (adjusted odds ratio = 3.15, 95% confidence interval = 2.12-4.67, P < 0.0001). When the cases were categorized by tumor histology, the effect of short telomere length on the risk of lung cancer was more pronounced in patients with small cell carcinoma than in those with squamous cell carcinoma and adenocarcinoma (P = 0.001, test for homogeneity). These findings suggest that shortening of the telomeres may be a risk factor for lung cancer, and therefore, the presence of shortened telomeres may be used as a marker for susceptibility to lung cancer.

  20. Social defeat stress promotes tumor growth and angiogenesis by upregulating vascular endothelial growth factor/extracellular signal-regulated kinase/matrix metalloproteinase signaling in a mouse model of lung carcinoma.

    PubMed

    Wu, Xiao; Liu, Bao-Jun; Ji, Shumeng; Wu, Jing-Feng; Xu, Chang-Qing; Du, Yi-Jie; You, Xiao-Fang; Li, Bei; Le, Jing-Jing; Xu, Hai-Lin; Duan, Xiao-Hong; Dong, Jing-Cheng

    2015-07-01

    Numerous epidemiological and experimental animal studies have indicated that chronic psychological stress may promote tumor development. However, the underlying molecular mechanisms by which chronic stress promotes tumorigenesis remain to be fully elucidated and animal models have not yet been well established. In the present study, an established mouse model of repeated social defeat stress (RSDS), was generated and used to investigate the effect of stress on tumor growth and metastasis. C57BL/6 mice were exposed to RSDS for 10 days, followed by subcutaneousl inoculation with Lewis lung carcinoma cells for seven days. The tumor weight and volume as well as the number of the lung metastatic nodules were then determined. Vascular endothelial growth factor (VEGF) serum levels were measured using ELISAs. In addition, expression levels of VEGF receptor (VEGFR) and L1 cell adhesion molecule (L1CAM) messenger (m)RNA were confirmed using reverse transcription quantitative polymerase chain reaction. Furthermore, protein expression levels of phosphorlyated extracellular signal-regulated kinase (pERK), matrix metalloproteinase (MMP)-2 and MMP-9 were examined using western blot analysis. The results showed that RSDS significantly increased the weight and the volume of the primary tumor as well as the number of the lung metastatic nodules. Serum VEGF levels were significantly higher in the tumor-stress group compared with those of the unstressed tumor mice. In addition, tumors in stressed animals demonstrated markedly enhanced expression of VEGFR-2 and L1CAM mRNA as well as pERK, MMP-2 and MMP-9 protein expression. In conclusion, these results suggested that RSDS contributed to lung cancer progression, angiogenesis and metastasis, which was partially associated with increased VEGF secretion and therefore the activation of the ERK signaling pathway, resulting in the induction of MMP-2 and MMP-9 protein expression. PMID:25824133

  1. Chemotherapy of non-small cell lung carcinoma guided by an in vitro drug resistance assay measuring total tumour cell kill.

    PubMed Central

    Wilbur, D. W.; Camacho, E. S.; Hilliard, D. A.; Dill, P. L.; Weisenthal, L. M.

    1992-01-01

    Specimens from 45 patients with previously-untreated non-small cell lung cancer (NSCLC) were tested for in vitro chemosensitivity to ten drugs utilising the DiSC assay, which measures cell kill in the total (largely non-dividing) tumour cell population. Thirty-five assays were successful and 25 patients with advanced disease subsequently received chemotherapy with the 'best' three drugs selected by the assay. Six patients were Karnofsky performance status 60 or less and the median pretreatment weight loss was 8.5%. Nine patients had a partial response (response rate = 36%; 95% confidence interval = 17-55%) and the median survival of all patients was 202 days. Specimens from responding patients were significantly more sensitive in the assay to drugs in general (especially to etoposide and to 'natural product' drugs) and to the drugs used in treatment than were specimens from non-responding patients. In vitro drug resistance differences between responding and non-responding patients were of greater significance than were differences between other clinical and laboratory measurements. Assay results classified patients into two cohorts, having relatively high and low probabilities of responding to chemotherapy. Assay results also identified patient cohorts with above average and below average durations of survival. Five patients (20%) were found to have tumours with extreme drug resistance (EDR), defined as assay results for the average of all ten tested drugs falling greater than one standard deviation more resistant than the median for all tumours assayed, and none of these patients with EDR responded to chemotherapy. PMID:1310250

  2. The causal relevance of body mass index in different histological types of lung cancer: A Mendelian randomization study.

    PubMed

    Carreras-Torres, Robert; Haycock, Philip C; Relton, Caroline L; Martin, Richard M; Smith, George Davey; Kraft, Peter; Gao, Chi; Tworoger, Shelley