NCI Alliance for Nanotechnology in Cancer

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The NCI Alliance for Nanotechnology in Cancer funds the Cancer Nanotechnology Training Centers collectively with the NCI Cancer Training Center. Find out about the funded Centers, to date, that train our next generation of scientists in the field of Canc

TGF-β of lung cancer microenvironment upregulates B7H1 and GITRL expression in dendritic cells and is associated with regulatory T cell generation.

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Ni, Xiao Yan; Sui, Hua Xiu; Liu, Yao; Ke, Shi Zhong; Wang, Yi Nan; Gao, Feng Guang

2012-08-01

The effects of TGF-β on dendritic cells (DCs) on the tumor microenvironment are not well understood. We report, here, the establishment of an in vitro lung cancer microenvironment by co-incubation of seminaphtharhodafluor (SNARF) labeled Lewis lung cancer (LLC) cells, carboxyfluorescein succinimidyl ester (CFSE) labeled fibroblasts and 4-chloromethyl-7-hydroxycoumarin (CMHC) labeled DCs. Raw 264.7, EL4 and NCI-H446 cells were able to synthesize TGF-β which was determined by flow cyto-metry and western blotting, respectively. Furthermore, TGF-β efficiently increased regulatory T-cell (Treg) expansion and upregulated DC B7H1 and GITRL expression. TGF-β and the co-incubation of LLC cells, fibroblasts with DCs could augment the expression of B7H1 and GITRL molecules of DCs. The data presented here indicate that the B7H1 and GITRL molecules may play an important role in TGF-β-induced Treg expansion of lung cancer microenvironment.

Cypripedin, a phenanthrenequinone from Dendrobium densiflorum, sensitizes non-small cell lung cancer H460 cells to cisplatin-mediated apoptosis.

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Wattanathamsan, Onsurang; Treesuwan, Surassawadee; Sritularak, Boonchoo; Pongrakhananon, Varisa

2018-03-01

The life-threatening potential of lung cancer has increased over the years due to its acquisition of chemotherapeutic resistance, especially to cisplatin, a first-line therapy. In response to this development, researchers have turned their attention to several compounds derived from natural origins, including cypripedin (CYP), a phenanthrenequinone substance extracted from Dendrobium densiflorum. The aim of the present study was to investigate the ability of CYP to induce apoptosis and enhance cisplatin-mediated death of human lung cancer NCI-H460 cells using cell viability and apoptosis assays. The induction of apoptosis by CYP was observed at a concentration of > 50 μM with the appearance of morphological changes, including DNA condensation and chromatin fragmentation. Together with, CYP was able to activate caspase-3 and downregulate the anti-apoptotic proteins Bcl-2 and Bcl-xL. Also, a non-cytotoxic dose of CYP synergistically potentiated the effect of cisplatin in non-small cell lung cancer line H460 cells, which clearly exhibited the apoptotic phenotype. Western blot analysis revealed that the underlying mechanism involved the downregulation of anti-apoptotic Bcl-xL, whereas the levels of other apoptotic regulatory proteins were not altered. This study provides interesting information on the potent effect of CYP as a chemotherapeutic sensitizer that could be further developed to improve the clinical outcomes of lung cancer patients.

Lung Cancer, Questions to Ask Your Health Professional | NIH MedlinePlus the Magazine

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... of this page please turn Javascript on. Feature: Lung Cancer Questions to Ask Your Health Professional Past Issues / ... answer questions about cancer at 1-800-4-CANCER. The NCI Lung Cancer Home Page provides up-to-date information ...

Which risk models perform best in selecting ever-smokers for lung cancer screening?

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A new analysis by scientists at NCI evaluates nine different individualized lung cancer risk prediction models based on their selections of ever-smokers for computed tomography (CT) lung cancer screening.

Preparation of oligonucleotide microarray for radiation-associated gene expression detection and its application in lung cancer cell lines

International Nuclear Information System (INIS)

Guo Wanfeng; Lin Ruxian; Huang Jian; Guo Guozhen; Wang Shengqi

2005-01-01

Objective: The response of tumor cell to radiation is accompanied by complex change in patterns of gene expression. It is highly probable that a better understanding of molecular and genetic changes can help to sensitize the radioresistant tumor cells. Methods: Oligonucleotide microarray provides a powerful tool for high-throughput identifying a wider range of genes involved in the radioresistance. Therefore, the authors designed one oligonucleotide microarray according to the biological effect of IR. By using different radiosensitive lung cancer cell lines, the authors identified genes showing altered expression in lung cancer cell lines. To provide independent confirmation of microarray data, semi-quantitative RT-PCR was performed on a selection of genes. Results: In radioresistant A549 cell lines, a total of 18 genes were selected as having significant fold-changes compared to NCI-H446, 8 genes were up-regulated and 10 genes were down-regulated. Subsequently, A549 and NCI-H446 cells were delivered by ionizing radiation. In A549 cell line, we found 22 (19 up-regulated and 3 down-regulated) and 26 (8 up-regulated and 18 down-regulated) differentially expressed genes at 6h and 24h after ionizing radiation. In NCI-H446 cell line, we identified 17 (9 up-regulated and 8 down-regulated) and 18 (6 up-regulated and 12 down-regulated) differentially expressed genes at 6 h and 24 h after ionizing radiation. The authors tested seven genes (MDM2, p53, XRCC5, Bcl-2, PIM2, NFKBIA and Cyclin B1) for RT-PCR, and found that the results were in good agreement with those from the microarray data except for NFKBIA gene, even though the value for each mRNA level might be different between the two measurements. In present study, the authors identified some genes with cell proliferation and anti-apoptosis, such as MdM2, BCL-2, PKCz and PIM2 expression levels increased in A549 cells and decreased in NCI-H446 cells after radiation, and other genes with DNA repair, such as XRCC5, ERCC5

Characterization of the effects of cyclooxygenase-2 inhibition in the regulation of apoptosis in human small and non-small cell lung cancer cell lines.

LENUS (Irish Health Repository)

Alam, Mahmood

2012-02-03

BACKGROUND: Cyclooxygenase-2 enzyme (COX-2) is overexpressed in human non-small cell lung cancer (NSCLC) but is not expressed in small cell lung cancer. Selective COX-2 inhibitors have been shown to induce apoptosis in NSCLC cells, an effect which is associated with the regulation of intracellular MAP kinase (MAPK) signal pathways. Our aims were to characterize the effects of COX-2 inhibition by rofecoxib on apoptosis in human NSCLC and small cell lung cancer cell lines. METHODS: The human NSCLC cell line NCI-H2126 and small cell lung cancer cell line DMS-79 were used. Constitutive COX-2 protein levels were first determined by Western blot test. Levels of apoptosis were evaluated by using propidium iodide staining on FACScan analysis after incubation of NCI-H2126 and DMS-79 with p38 MAPK inhibitor SB202190 (25 ?microM), NF-kappaB inhibitor SN50 (75 microg\\/mL), and rofecoxib at 100 and 250 microM. All statistical analysis was performed by analysis of variance. RESULTS: Western blot test confirmed the presence of COX-2 enzyme in NCI-H2126 and absence in DMS-79. Interestingly, rofecoxib treatment demonstrated a dose-dependent increase in apoptosis in both cell lines. Given this finding, the effect of rofecoxib on NF-kappaB and p38 MAPK pathways was also examined. Apoptosis in both cell lines was unaltered by SN50, either alone or in combination with rofecoxib. A similar phenomenon was observed in NCI-H2126 cells treated with SB202190, either alone or in combination with rofecoxib. In contrast, p38 MAPK inhibition greatly upregulated DMS-79 apoptosis in a manner that was unaltered by the addition of rofecoxib. CONCLUSIONS: Rofecoxib led to a dose-dependent increase in apoptosis in both tumor cell lines. This effect occurred independently of COX-2, NF-kappaB, and p38 MAPK pathways in DMS-79 cells. As such, rofecoxib must act on alternative pathways to regulate apoptosis in human small cell lung cancer cells.

Electromechanical transducer for rapid detection, discrimination and quantification of lung cancer cells

International Nuclear Information System (INIS)

Ali, Waqas; Raza, Muhammad Usman; Iqbal, Samir M; Moghaddam, Fatemeh Jalvhei; Bui, Loan; Sayles, Bailey; Kim, Young-Tae

2016-01-01

Tumor cells are malignant derivatives of normal cells. There are characteristic differences in the mechanophysical properties of normal and tumor cells, and these differences stem from the changes that occur in the cell cytoskeleton during cancer progression. There is a need for viable whole blood processing techniques for rapid and reliable tumor cell detection that do not require tagging. Micropore biosensors have previously been used to differentiate tumor cells from normal cells and we have used a micropore-based electromechanical transducer to differentiate one type of tumor cells from the other types. This device generated electrical signals that were characteristic of the cell properties. Three non-small cell lung cancer (NSCLC) cell lines, NCl-H1155, A549 and NCI-H460, were successfully differentiated. NCI-H1155, due to their comparatively smaller size, were found to be the quickest in translocating through the micropore. Their translocation through a 15 μm micropore caused electrical pulses with an average translocation time of 101 ± 9.4 μs and an average peak amplitude of 3.71 ± 0.42 μA, whereas translocation of A549 and NCI-H460 caused pulses with average translocation times of 126 ± 17.9 μs and 148 ± 13.7 μs and average peak amplitudes of 4.58 ± 0.61 μA and 5.27 ± 0.66 μA, respectively. This transformation of the differences in cell properties into differences in the electrical profiles (i.e. the differences in peak amplitudes and translocation times) with this electromechanical transducer is a quantitative way to differentiate these lung cancer cells. The solid-state micropore device processed whole biological samples without any pre-processing requirements and is thus ideal for point-of-care applications. (paper)

Fisetin induces apoptosis and endoplasmic reticulum stress in human non-small cell lung cancer through inhibition of the MAPK signaling pathway.

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Kang, Kyoung Ah; Piao, Mei Jing; Madduma Hewage, Susara Ruwan Kumara; Ryu, Yea Seong; Oh, Min Chang; Kwon, Taeg Kyu; Chae, Sungwook; Hyun, Jin Won

2016-07-01

Fisetin (3,3',4',7-tetrahydroxyflavone), a dietary flavonoid compound, is currently being investigated for its anticancer effect in various cancer models, including lung cancer. Recent studies show that fisetin induces cell growth inhibition and apoptosis in the human non-small cell lung cancer line NCI-H460. In this study, we investigated whether fisetin can induce endoplasmic reticulum (ER) stress-mediated apoptosis in NCI-H460 cells. Fisetin induced mitochondrial reactive oxygen species (ROS) and characteristic signs of ER stress: ER staining; mitochondrial Ca(2+) overload; expression of ER stress-related proteins; glucose-regulated protein (GRP)-78, phosphorylation of protein kinase RNA (PKR)-like endoplasmic reticulum kinase (PERK) and phosphorylation of eukaryotic initiation factor-2 α subunit; cleavage of activating transcription factor-6; phosphorylation of inositol-requiring kinase-1 and splicing of X-box transcription factor-1; induction of C/EBP homologous protein and cleaved caspase-12. siRNA-mediated knockdown of CHOP and ATF-6 attenuated fisetin-induced apoptotic cell death. In addition, fisetin induced phosphorylation of ERK, JNK, and p38 MAPK. Moreover, silencing of the MAPK signaling pathway prevented apoptotic cell death. In summary, our results indicate that, in NCI-H460 cells, fisetin induces apoptosis and ER stress that is mediated by induction of the MAPK signaling pathway.

Dithiolethione modified valproate and diclofenac increase E-cadherin expression and decrease proliferation of non-small cell lung cancer cells

OpenAIRE

Moody, Terry W.; Switzer, Christopher; Santana-Flores, Wilmarie; Ridnour, Lisa A.; Berna, Marc; Thill, Michelle; Jensen, Robert T.; Sparatore, Anna; Del Soldato, Piero; Yeh, Grace C; Roberts, David D.; Giaccone, Giuseppe; Wink, David A.

2009-01-01

The effects of dithiolethione-modified valproate, diclofenac and sulindac on non-small cell lung cancer (NSCLC) cells were investigated. Sulfur(S)-valproate and S-diclofenac at 1 μg/ml concentrations significantly reduced prostaglandin (PG)E2 levels in NSCLC cell lines A549 and NCI-H1299 as did the COX-2 inhibitor DuP-697. In vitro, S-valproate, S-diclofenac and S-sulindac half-maximally inhibited the clonal growth of NCI-H1299 cells at 6, 6 and 15 μg/ml, respectively. Using the MTT assay, 10...

Find an NCI-Designated Cancer Center

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Find the locations of NCI-designated cancer centers by area, region, state, or name that includes contact information to help health care providers and cancer patients with referrals to clinical trials.

76 FR 41805 - Submission for OMB Review; Comment Request; Prostate, Lung, Colorectal and Ovarian Cancer...

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2011-07-15

... mortality for each of the four cancer sites (prostate, lung, colorectal, and ovary). In addition, cancer...; Comment Request; Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO) (NCI) SUMMARY: Under the provisions of Section 3507(a)(1)(D) of the Paperwork Reduction Act of 1995, the National Cancer...

Expression and Activity of Breast Cancer Resistance Protein (BCRP/ABCG2) in Human Distal Lung Epithelial Cells In Vitro.

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Nickel, Sabrina; Selo, Mohammed Ali; Fallack, Juliane; Clerkin, Caoimhe G; Huwer, Hanno; Schneider-Daum, Nicole; Lehr, Claus-Michael; Ehrhardt, Carsten

2017-12-01

Breast cancer resistance protein (BCRP/ABCG2) has previously been identified with high expression levels in human lung. The subcellular localisation and functional activity of the transporter in lung epithelia, however, remains poorly investigated. The aim of this project was to study BCRP expression and activity in freshly isolated human alveolar epithelial type 2 (AT2) and type 1-like (AT1-like) cells in primary culture, and to compare these findings with data obtained from the NCI-H441 cell line. BCRP expression levels in AT2 and AT1-like cells and in different passages of NCI-H441 cells were determined using q-PCR and immunoblot. Transporter localisation was confirmed by confocal laser scanning microscopy. Efflux and transport studies using the BCRP substrate BODIPY FL prazosin and the inhibitor Ko143 were carried out to assess BCRP activity in the different cell models. BCRP expression decreased during transdifferentiation from AT2 to AT1-like phenotype. Culturing NCI-H441 cells at an air-liquid interface or submersed did not change BCRP abundance, however, BCRP levels increased with passage number. BCRP was localised to the apical membrane and cytosol in NCI-H441 cells. In primary cells, the protein was found predominantly in the nucleus. Functional studies were consistent with expression data. BCRP is differently expressed in AT2 and AT1-like cells with lower abundance and activity in the latter ones. Nuclear BCRP might play a transcriptional role in distal lung epithelium. In NCI-H441 cells, BCRP is expressed in apical cell membranes and its activity is consistent with the localisation pattern.

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

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Date Hiroshi

2007-01-01

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

Low-Dose Radiation Induces Cell Proliferation in Human Embryonic Lung Fibroblasts but not in Lung Cancer Cells

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Xinyue Liang

2016-01-01

Full Text Available Hormesis and adaptive responses are 2 important biological effects of low-dose ionizing radiation (LDR. In normal tissue, LDR induces hormesis as evinced by increased cell proliferation; however, whether LDR also increases tumor cell proliferation needs to be investigated. In this study, cell proliferation was assayed by total cell numbers and the Cell Counting Kit 8 assay. Mitogen-activated protein kinases (MAPK/extracellular signal-regulated kinase (ERK and phosphatidylinositol 3′ -kinase(PI3K-Akt (PI3K/AKT phosphorylation were determined by Western blot analysis. Human embryonic lung fibroblast 2BS and lung cancer NCI-H446 cell lines were irradiated with LDR at different doses (20-100 mGy. In response to 20 to 75 mGy X-rays, cell proliferation was significantly increased in 2BS but not in NCI-H446 cells. In 2BS cells, LDR at 20 to 75 mGy also stimulated phosphorylation of MAPK/ERK pathway proteins including ERK, MEK, and Raf and of the PI3K/AKT pathway protein AKT. To test whether ERK1/2 and AKT pathway activation was involved in the stimulation of cell proliferation in 2BS cells, the MAPK/ERK and PI3K/AKT pathways were inhibited using their specific inhibitors, U0126 and LY294002. U0126 decreased the phosphorylation of ERK1/2, and LY294002 decreased the phosphorylation of AKT; each could significantly inhibit LDR-induced 2BS cell proliferation. However, LDR did not stimulate these kinases, and kinase inhibitors also did not affect cell proliferation in the NCI-H446 cells. These results suggest that LDR stimulates cell proliferation via the activation of both MAPK/ERK and PI3K/AKT signaling pathways in 2BS but not in NCI-H446 cells. This finding implies the potential for applying LDR to protect normal tissues from radiotherapy without diminishing the efficacy of tumor therapy.

76 FR 28439 - Submission for OMB Review; Comment Request; NCI Cancer Genetics Services Directory Web-Based...

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2011-05-17

...; Comment Request; NCI Cancer Genetics Services Directory Web-Based Application Form and Update Mailer... currently valid OMB control number. Proposed Collection: Title: NCI Cancer Genetics Services Directory Web... included in the NCI Cancer Genetics Services Directory on NCI's Cancer.gov Web site. The information...

The In Vitro Anti-Tumor Activity of Phycocyanin against Non-Small Cell Lung Cancer Cells

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Shuai Hao

2018-05-01

Full Text Available Phycocyanin, a type of functional food colorant, is shown to have a potent anti-cancer property. Non-small cell lung cancer (NSCLC is one of the most aggressive form of cancers with few effective therapeutic options. Previous studies have demonstrated that phycocyanin exerts a growth inhibitory effect on NSCLC A549 cells. However, its biological function and underlying regulatory mechanism on other cells still remain unknown. Here, we investigated the in vitro function of phycocyanin on three typical NSCLC cell lines, NCI-H1299, NCI-H460, and LTEP-A2, for the first time. The results showed that phycocyanin could significantly induce apoptosis, cell cycle arrest, as well as suppress cell migration, proliferation, and the colony formation ability of NSCLC cells through regulating multiple key genes. Strikingly, phycocyanin was discovered to affect the cell phenotype through regulating the NF-κB signaling of NSCLC cells. Our findings demonstrated the anti-neoplastic function of phycocyanin and provided valuable information for the regulation of phycocyanin in NSCLC cells.

ImmunoPET for assessing the differential uptake of a CD146-specific monoclonal antibody in lung cancer

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Sun, Haiyan; Kamkaew, Anyanee; Jiang, Dawei; Yang, Yunan [University of Wisconsin-Madison, Department of Radiology, Madison, WI (United States); England, Christopher G.; Hernandez, Reinier; Graves, Stephen A.; Barnhart, Todd E. [University of Wisconsin-Madison, Department of Medical Physics, Madison, WI (United States); Majewski, Rebecca L. [University of Wisconsin-Madison, Department of Biomedical Engineering, Madison, WI (United States); Cai, Weibo [University of Wisconsin-Madison, Department of Radiology, Madison, WI (United States); University of Wisconsin-Madison, Department of Medical Physics, Madison, WI (United States); University of Wisconsin-Madison, Department of Biomedical Engineering, Madison, WI (United States); University of Wisconsin Carbone Cancer Center, Madison, WI (United States)

2016-11-15

Overexpression of CD146 in solid tumors has been linked to disease progression, invasion, and metastasis. We describe the generation of a {sup 64}Cu-labeled CD146-specific antibody and its use for quantitative immunoPET imaging of CD146 expression in six lung cancer models. The anti-CD146 antibody (YY146) was conjugated to 1,4,7-triazacyclononane-triacetic acid (NOTA) and radiolabeled with {sup 64}Cu. CD146 expression was evaluated in six human lung cancer cell lines (A549, NCI-H358, NCI-H522, HCC4006, H23, and NCI-H460) by flow cytometry and quantitative western blot studies. The biodistribution and tumor uptake of {sup 64}Cu-NOTA-YY146 was assessed by sequential PET imaging in athymic nude mice bearing subcutaneous lung cancer xenografts. The correlation between CD146 expression and tumor uptake of {sup 64}Cu-NOTA-YY146 was evaluated by graphical software while ex vivo biodistribution and immunohistochemistry studies were performed to validate the accuracy of PET data and spatial expression of CD146. Flow cytometry and western blot studies showed similar findings with H460 and H23 cells showing high levels of expression of CD146. Small differences in CD146 expression levels were found among A549, H4006, H522, and H358 cells. Tumor uptake of {sup 64}Cu-NOTA-YY146 was highest in CD146-expressing H460 and H23 tumors, peaking at 20.1 ± 2.86 and 11.6 ± 2.34 %ID/g at 48 h after injection (n = 4). Tumor uptake was lowest in the H522 model (4.1 ± 0.98 %ID/g at 48 h after injection; n = 4), while H4006, A549 and H358 exhibited similar uptake of {sup 64}Cu-NOTA-YY146. A positive correlation was found between tumor uptake of {sup 64}Cu-NOTA-YY146 (%ID/g) and relative CD146 expression (r {sup 2} = 0.98, p < 0.01). Ex vivo biodistribution confirmed the accuracy of the PET data. The strong correlation between tumor uptake of {sup 64}Cu-NOTA-YY146 and CD146 expression demonstrates the potential use of this radiotracer for imaging tumors that elicit varying levels of CD146

The NCI Digital Divide Pilot Projects: implications for cancer education.

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Kreps, Gary L; Gustafson, David; Salovey, Peter; Perocchia, Rosemarie Slevin; Wilbright, Wayne; Bright, Mary Anne; Muha, Cathy

2007-01-01

The National Cancer Institute (NCI) supported four innovative demonstration research projects, "The Digital Divide Pilot Projects," to test new strategies for disseminating health information via computer to vulnerable consumers. These projects involved active research collaborations between the NCI's Cancer Information Service (CIS) and regional cancer control researchers to field test new approaches for enhancing cancer communication in vulnerable communities. The projects were able to use computers to successfully disseminate relevant cancer information to vulnerable populations. These demonstration research projects suggested effective new strategies for using communication technologies to educate underserved populations about cancer prevention, control, and care.

UNC Cancer Center Director to Lead NCI.

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2017-08-01

President Donald Trump has selected Norman "Ned" Sharpless, MD, director of the University of North Carolina Lineberger Comprehensive Cancer Center, to lead the NCI. The news was met with widespread approval among cancer researchers, who view Sharpless as a strong communicator who can ably represent the needs of the cancer community in the face of proposed funding cuts. ©2017 American Association for Cancer Research.

Inactivated Tianjin strain, a novel genotype of Sendai virus, induces apoptosis in HeLa, NCI-H446 and Hep3B cells.

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Chen, Jun; Han, Han; Wang, Bin; Shi, Liying

2016-07-01

The Sendai virus strain Tianjin is a novel genotype of the Sendai virus. In previous studies, ultraviolet-inactivated Sendai virus strain Tianjin (UV-Tianjin) demonstrated antitumor effects on human breast cancer cells. The aim of the present study was to investigate the in vitro antitumor effects of UV-Tianjin on the human cervical carcinoma HeLa, human small cell lung cancer NCI-H446 and human hepatocellular carcinoma Hep 3B cell lines, and the possible underlying mechanisms of these antitumor effects. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay revealed that UV-Tianjin treatment inhibited the proliferation of HeLa, NCI-H446 and Hep 3B cells in a dose- and time-dependent manner. Hoechst and Annexin V-fluorescein isothiocyanate/propidium iodide double staining indicated that UV-Tianjin induced dose-dependent apoptosis in all three cell lines with the most significant effect observed in the HeLa cell line. In the HeLa cell line, UV-Tianjin-induced apoptosis was further confirmed by the disruption of the mitochondria membrane potential and the activation of caspases, as demonstrated by fluorescent cationic dye and colorimetric assays, respectively. In addition, western blot analysis revealed that UV-Tianjin treatment resulted in significant upregulation of cytochrome c , apoptosis protease activating factor-1, Fas, Fas ligand and Fas-associated protein with death domain, and activated caspase-9, -8 and -3 in HeLa cells. Based on these results, it is hypothesized that UV-Tianjin exhibits anticancer activity in HeLa, NCI-H446 and Hep 3B cell lines via the induction of apoptosis. In conclusion, the results of the present study indicate that in the HeLa cell line, intrinsic and extrinsic apoptotic pathways may be involved in UV-Tianjin-induced apoptosis.

Published Research - NCI Alliance for Nanotechnology in Cancer

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The NCI Alliance for Nanotechnology in Cancer has published much exciting and impactful research over the years. Find here a list of all of these listed in PubMed and others across the field of Cancer Nanotechnology.

Quantitative Secretomic Analysis Identifies Extracellular Protein Factors That Modulate the Metastatic Phenotype of Non-Small Cell Lung Cancer.

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Hu, Rongkuan; Huffman, Kenneth E; Chu, Michael; Zhang, Yajie; Minna, John D; Yu, Yonghao

2016-02-05

Lung cancer is the leading cause of cancer-related deaths for men and women in the United States, with non-small cell lung cancer (NSCLC) representing 85% of all diagnoses. Late stage detection, metastatic disease and lack of actionable biomarkers contribute to the high mortality rate. Proteins in the extracellular space are known to be critically involved in regulating every stage of the pathogenesis of lung cancer. To investigate the mechanism by which secreted proteins contribute to the pathogenesis of NSCLC, we performed quantitative secretomic analysis of two isogenic NSCLC cell lines (NCI-H1993 and NCI-H2073) and an immortalized human bronchial epithelial cell line (HBEC3-KT) as control. H1993 was derived from a chemo-naïve metastatic tumor, while H2073 was derived from the primary tumor after etoposide/cisplatin therapy. From the conditioned media of these three cell lines, we identified and quantified 2713 proteins, including a series of proteins involved in regulating inflammatory response, programmed cell death and cell motion. Gene Ontology (GO) analysis indicates that a number of proteins overexpressed in H1993 media are involved in biological processes related to cancer metastasis, including cell motion, cell-cell adhesion and cell migration. RNA interference (RNAi)-mediated knock down of a number of these proteins, including SULT2B1, CEACAM5, SPRR3, AGR2, S100P, and S100A14, leads to dramatically reduced migration of these cells. In addition, meta-analysis of survival data indicates NSCLC patients whose tumors express higher levels of several of these secreted proteins, including SULT2B1, CEACAM5, SPRR3, S100P, and S100A14, have a worse prognosis. Collectively, our results provide a potential molecular link between deregulated secretome and NSCLC cell migration/metastasis. In addition, the identification of these aberrantly secreted proteins might facilitate the development of biomarkers for early detection of this devastating disease.

Lentivirus-mediated knockdown of NLK inhibits small-cell lung cancer growth and metastasis

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Lv MT

2016-11-01

Full Text Available Mutian Lv,1 Yaming Li,1 Xin Tian,2 Shundong Dai,3,4 Jing Sun,5 Guojiang Jin,6 Shenyi Jiang7 1Department of Nuclear Medicine, 2Molecular Oncology Laboratory of Cancer Research Institute, The First Affiliated Hospital of China Medical University, 3Department of Pathology, The First Affiliated Hospital, College of Basic Medical Sciences of China Medical University, 4Department of Pathology, Institute of Pathology and Pathophysiology, 5Department of Immunology and Biotherapy, Liaoning Cancer Hospital and Institute, 6Department of Laboratory Medicine, 7Department of Rheumatology, The First Affiliated Hospital of China Medical University, Shenyang, People’s Republic of China Abstract: Nemo-like kinase (NLK, an evolutionarily conserved serine/threonine kinase, has been recognized as a critical regulator of various cancers. In this study, we investigated the role of NLK in human small-cell lung cancer (SCLC, which is the most aggressive form of lung cancer. NLK expression was evaluated by quantitative real-time polymerase chain reaction in 20 paired fresh SCLC tissue samples and found to be noticeably elevated in tumor tissues. Lentivirus-mediated RNAi efficiently suppressed NLK expression in NCI-H446 cells, resulting in a significant reduction in cell viability and proliferation in vitro. Moreover, knockdown of NLK led to cell cycle arrest at the S-phase via suppression of Cyclin A, CDK2, and CDC25A, which could contribute to cell growth inhibition. Furthermore, knockdown of NLK decreased the migration of NCI-H446 cells and downregulated matrix metalloproteinase 9. Treatment with NLK short hairpin RNA significantly reduced SCLC tumor growth in vivo. In conclusion, this study suggests that NLK plays an important role in the growth and metastasis of SCLC and may serve as a potential therapeutic target for the treatment of SCLC. Keywords: NLK, SCLC, RNAi, proliferation, migration

Study finds stronger nicotine dependency associated with higher risk of lung cancer

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NCI headed study finds people who are highly addicted to nicotine -- those who smoke their first cigarette within five minutes after awakening -- are at higher risk of developing lung cancer than those who wait for an hour or more to smoke.

Lung Cancer Susceptibility and hOGG1 Ser326Cys Polymorphism: A Meta-Analysis

International Nuclear Information System (INIS)

Kiyohara, Chikako; Takayama, Koichi; Nakanishi, Yoichi

2010-01-01

Recent lung cancer studies have focused on identifying the effects of single nucleotide polymorphisms (SNPs) in candidate genes, among which DNA repair genes are increasingly being studied. Genetic variations in DNA repair genes are thought to modulate DNA repair capacity and are suggested to be related to lung cancer risk. In this study, we tried to assess reported studies of association between polymorphism of human 8-oxoguanine DNA glycosylase 1 (hOGG1) Ser326Cys and lung cancer. We conducted MEDLINE, Current Contents and Web of Science searches using 'hOGG1', 'lung cancer' and 'polymorphism' as keywords to search for papers published (from January 1995 through August 2010). Data were combined using both a fixed effects (the inverse variance-weighted method) and a random effects (DerSimonian and Laird method) models. The Cochran Q test was used for the assessment of heterogeneity. Publication bias was assessed by both Begg’s and Egger’s tests. We identified 20 case-control studies in 21 different ethnic populations. As two studies were not in the Hardy-Weinberg equilibrium, 18 case-control studies in 19 different ethnic populations (7,792 cases and 9,358 controls) were included in our meta-analysis. Summary frequencies of the Cys allele among Caucasians and Asians based on the random effects model were 20.9% (95% confidence interval (CI) = 18.9–22.9) and 46.1% (95% CI = 40.2–52.0), respectively. The distribution of the Cys allele was significantly different between Asians and Caucasians (P < 0.001). The Cys/Cys genotype was significantly associated with lung cancer risk in Asian populations (odds ratio = 1.27, 95% CI = 1.09–1.48) but not in Caucasian populations. This ethnic difference in lung cancer risk may be due to environmental factors such as cigarette smoking and dietary factors. Although the summary risk for developing lung cancer may not be large, lung cancer is such a common malignancy that even a small increase

Lung Cancer Susceptibility and hOGG1 Ser326Cys Polymorphism: A Meta-Analysis

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Kiyohara, Chikako, E-mail: chikako@phealth.med.kyushu-u.ac.jp [Department of Preventive Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Takayama, Koichi; Nakanishi, Yoichi [Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan)

2010-10-28

Recent lung cancer studies have focused on identifying the effects of single nucleotide polymorphisms (SNPs) in candidate genes, among which DNA repair genes are increasingly being studied. Genetic variations in DNA repair genes are thought to modulate DNA repair capacity and are suggested to be related to lung cancer risk. In this study, we tried to assess reported studies of association between polymorphism of human 8-oxoguanine DNA glycosylase 1 (hOGG1) Ser326Cys and lung cancer. We conducted MEDLINE, Current Contents and Web of Science searches using 'hOGG1', 'lung cancer' and 'polymorphism' as keywords to search for papers published (from January 1995 through August 2010). Data were combined using both a fixed effects (the inverse variance-weighted method) and a random effects (DerSimonian and Laird method) models. The Cochran Q test was used for the assessment of heterogeneity. Publication bias was assessed by both Begg’s and Egger’s tests. We identified 20 case-control studies in 21 different ethnic populations. As two studies were not in the Hardy-Weinberg equilibrium, 18 case-control studies in 19 different ethnic populations (7,792 cases and 9,358 controls) were included in our meta-analysis. Summary frequencies of the Cys allele among Caucasians and Asians based on the random effects model were 20.9% (95% confidence interval (CI) = 18.9–22.9) and 46.1% (95% CI = 40.2–52.0), respectively. The distribution of the Cys allele was significantly different between Asians and Caucasians (P < 0.001). The Cys/Cys genotype was significantly associated with lung cancer risk in Asian populations (odds ratio = 1.27, 95% CI = 1.09–1.48) but not in Caucasian populations. This ethnic difference in lung cancer risk may be due to environmental factors such as cigarette smoking and dietary factors. Although the summary risk for developing lung cancer may not be large, lung cancer is such a common malignancy that even a small increase

Xylitol induces cell death in lung cancer A549 cells by autophagy.

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Park, Eunjoo; Park, Mi Hee; Na, Hee Sam; Chung, Jin

2015-05-01

Xylitol is a widely used anti-caries agent that has anti-inflammatory effects. We have evaluated the potential of xylitol in cancer treatment. It's effects on cell proliferation and cytotoxicity were measured by MTT assay and LDH assay. Cell morphology and autophagy were examined by immunostaining and immunoblotting. Xylitol inhibited cell proliferation in a dose-dependent manner in these cancer cells: A549, Caki, NCI-H23, HCT-15, HL-60, K562, and SK MEL-2. The IC50 of xylitol in human gingival fibroblast cells was higher than in cancer cells, indicating that it is more specific for cancer cells. Moreover, xylitol induced autophagy in A549 cells that was inhibited by 3-methyladenine, an autophagy inhibitor. These results indicate that xylitol has potential in therapy against lung cancer by inhibiting cell proliferation and inducing autophagy of A549 cells.

Bystander Effects Induced by Continuous Low-Dose-Rate 125I Seeds Potentiate the Killing Action of Irradiation on Human Lung Cancer Cells In Vitro

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Chen, H.H.; Jia, R.F.; Yu, L.; Zhao, M.J.; Shao, C.L.; Cheng, W.Y.

2008-01-01

Purpose: To investigate bystander effects of low-dose-rate (LDR) 125 I seed irradiation on human lung cancer cells in vitro. Methods and Materials: A549 and NCI-H446 cell lines of differing radiosensitivity were directly exposed to LDR 125 I seeds irradiation for 2 or 4 Gy and then cocultured with nonirradiated cells for 24 hours. Induction of micronucleus (MN), γH2AX foci, and apoptosis were assayed. Results: After 2 and 4 Gy irradiation, micronucleus formation rate (MFR) and apoptotic rate of A549 and NCI-H446 cells were increased, and the MFR and apoptotic rate of NCI-H446 cells was 2.1-2.8 times higher than that of A549 cells. After coculturing nonirradiated bystander cells with 125 I seed irradiated cells for 24 hours, MFR and the mean number of γH2AX foci/cells of bystander A549 and NCI-H446 cells were similar and significantly higher than those of control (p 125 I seeds could induce bystander effects, which potentiate the killing action on tumor cells and compensate for the influence of nonuniform distribution of radiation dosage on therapeutic outcomes

NCI International EBV-Gastric Cancer Consortium

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A collaboration among NCI and extramural investigators, established by DCEG in 2006, that utilizes data and biospecimens from completed and ongoing case series and observational studies of gastric cancer to replicate and extend findings from previous studies hindered by small numbers of EBV-positive cases, and to stimulate multidisciplinary research in this area.

TRX is up-regulated by fibroblast growth factor-2 in lung carcinoma.

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Deng, Zheng-Hao; Cao, Hui-Qiu; Hu, Yong-Bin; Wen, Ji-Fang; Zhou, Jian-Hua

2011-01-01

We have previously shown that exogenous fibroblast growth factor-2 (FGF-2) inhibits apoptosis of the small-cell lung cancer (SCLC) cell line NCI-H446, but the underlying mechanism remains unknown. In this study, the protein profiles of FGF-2-treated and untreated NCI-H446 cells were determined by 2-D gel electrophoresis combined with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and bioinformatics. Differential expression analysis of the protein profiles after FGF-2 treatment identified a total of 24 protein spots, of which nine were up-regulated and 15 were down-regulated. Four proteins were identified by MALDI-TOF-MS: thioredoxin (TRX), visfatin, ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) and Cu/Zn superoxide dismutase (CuZn-SOD). Western blotting revealed that TRX was up-regulated in NCI-H446 and A549 cells treated with FGF-2. Furthermore, immunohistochemical staining confirmed that both FGF-2 and TRX were overexpressed in lung cancer tissues and could be correlated with both lymph node metastasis and clinical stage. These data indicate that TRX may be involved in the FGF-2 signaling pathway. © 2010 The Authors. APMIS © 2010 APMIS.

Permissivity of the NCI-60 cancer cell lines to oncolytic Vaccinia Virus GLV-1h68

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Ascierto, Maria Libera; Bedognetti, Davide; Uccellini, Lorenzo; Rossano, Fabio; Ascierto, Paolo A; Stroncek, David F; Restifo, Nicholas P; Wang, Ena; Szalay, Aladar A; Marincola, Francesco M; Worschech, Andrea; Yu, Zhiya; Adams, Sharon; Reinboth, Jennifer; Chen, Nanhai G; Pos, Zoltan; Roychoudhuri, Rahul; Di Pasquale, Giovanni

2011-01-01

Oncolytic viral therapy represents an alternative therapeutic strategy for the treatment of cancer. We previously described GLV-1h68, a modified Vaccinia Virus with exclusive tropism for tumor cells, and we observed a cell line-specific relationship between the ability of GLV-1h68 to replicate in vitro and its ability to colonize and eliminate tumor in vivo. In the current study we surveyed the in vitro permissivity to GLV-1h68 replication of the NCI-60 panel of cell lines. Selected cell lines were also tested for permissivity to another Vaccinia Virus and a vesicular stomatitis virus (VSV) strain. In order to identify correlates of permissity to viral infection, we measured transcriptional profiles of the cell lines prior infection. We observed highly heterogeneous permissivity to VACV infection amongst the cell lines. The heterogeneity of permissivity was independent of tissue with the exception of B cell derivation. Cell lines were also tested for permissivity to another Vaccinia Virus and a vesicular stomatitis virus (VSV) strain and a significant correlation was found suggesting a common permissive phenotype. While no clear transcriptional pattern could be identified as predictor of permissivity to infection, some associations were observed suggesting multifactorial basis permissivity to viral infection. Our findings have implications for the design of oncolytic therapies for cancer and offer insights into the nature of permissivity of tumor cells to viral infection

The fibronectin III-1 domain activates a PI3-Kinase/Akt signaling pathway leading to αvβ5 integrin activation and TRAIL resistance in human lung cancer cells

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Cho, Christina; Horzempa, Carol; Jones, David; McKeown-Longo, Paula J.

2016-01-01

Fibronectin is a mechanically sensitive protein which is organized in the extracellular matrix as a network of interacting fibrils. The lung tumor stroma is enriched for fibronectin which is thought to contribute to metastasis and drug resistance. Fibronectin is an elastic, multi-modular protein made up of individually folded domains, some of which can stretch in response to increased mechanical tension. Very little is known about the relationship of fibronectin’s unfolded domains to lung cancer resistance to chemotherapy. In the present study, we evaluated the impact of unfolding the first Type III domain of fibronectin (FnIII-1c) on TNF-related apoptosis inducing ligand (TRAIL) resistance. NCI-H460 non-small cell lung cancer cells were treated with FnIII-1c then assessed for TRAIL-induced apoptosis. Subsequent analysis of FnIII-1c-mediated signaling pathways was also completed. Human non-small cell lung cancer tissue sections were assessed for the expression of vitronectin by immunohistochemistry. FnIII-1c inhibited TRAIL-induced activation of caspase 8 and subsequent apoptosis in NCI-H460 lung cancer cells. FnIII-1c treatment was associated with the activation of the phosphatidylinositol-3-kinase/alpha serine/threonine kinase (PI3K/Akt) pathway and the αvβ5 integrin receptor for vitronectin, both of which were required for TRAIL resistance. Immunohistochemical staining of sections from non-small cell lung cancers showed that vitronectin was localized around blood vessels and in the tumor-stroma interface. Unfolding of Type III domains within the fibronectin matrix may promote TRAIL resistance through the activation of a PI3K/Akt/αvβ5 signaling axis and point to a novel mechanism by which changes in secondary structure of fibronectin contribute to cancer cell resistance to apoptosis

Metabolic profiling of human lung cancer blood plasma using 1H NMR spectroscopy

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Kokova, Daria; Dementeva, Natalia; Kotelnikov, Oleg; Ponomaryova, Anastasia; Cherdyntseva, Nadezhda; Kzhyshkowska, Juliya

2017-11-01

Lung cancer (both small cell and non-small cell) is the second most common cancer in both men and women. The article represents results of evaluating of the plasma metabolic profiles of 100 lung cancer patients and 100 controls to investigate significant metabolites using 400 MHz 1H NMR spectrometer. The results of multivariate statistical analysis show that a medium-field NMR spectrometer can obtain the data which are already sufficient for clinical metabolomics.

Imaging and biodistribution of Her2/neu expression in non-small cell lung cancer xenografts with 64Cu-labeled trastuzumab PET

International Nuclear Information System (INIS)

Paudyal, P.; Paudyal, B.; Hanaoka, Hirofumi

2010-01-01

Non-small cell lung carcinomas (NSCLC) overexpress the Her2/neu gene in approximately 59% of cases. Trastuzumab, a humanized monoclonal antibody, interferes with Her2 signaling and is approved for the treatment of Her2/neu overexpressing breast cancer. However, its therapeutic use in Her2/neu overexpressing NSCLC remains obscure. The present study aimed to determine the role of 64 Cu-labeled trastuzumab positron emission tomography (PET) for non-invasive imaging of Her2/neu expression in NSCLC. Trastuzumab was conjugated with the bifunctional chelator 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA) and radiolabeled with 64 Cu. The molecular specificity of DOTA-trastuzumab was determined in NSCLC cell lines with Her2/neu overexpression (NCI-H2170) and negative expression (NCI-H520). Imaging of Her2/neu expression was performed in NCI-H2170 tumor-bearing mice with 64 Cu-DOTA-trastuzumab PET and 64 Cu-DOTA-immunoglobulin G (IgG). In vitro studies revealed specific binding of DOTA-trastuzumab in the Her2/neu positive NCI-H2170 cells, while no binding was seen in the Her2/neu negative NCI-H520 cell line. Biodistribution and PET studies revealed a significantly high accumulation of 64 Cu-DOTA-trastuzumab in the Her2/neu overexpressing NCI-H2170 tumor at 24 and 48 h post-injection (21.4±1.4% and 23.2±5.1% injection dose/gram (% ID/g), respectively). PET imaging of Her2/neu negative NCI-H520 tumors showed much less uptake of 64 Cu-DOTA-trastuzumab (4.0% ID/g). The NCI-H2170 tumor uptake of 64 Cu-DOTA-trastuzumab was significantly higher than that of 64 Cu-DOTA-IgG (P 64 Cu-DOTA-trastuzumab showed a very clear image of a Her2/neu positive tumor and appeared to be effective as a PET tracer for imaging of Her2/neu gene expression in NSCLC, suggesting its potential clinical use for identifying patients that might benefit from trastuzumab-based therapy. (author)

The NCI Alliance for Nanotechnology in Cancer: achievement and path forward.

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Ptak, Krzysztof; Farrell, Dorothy; Panaro, Nicholas J; Grodzinski, Piotr; Barker, Anna D

2010-01-01

Nanotechnology is a 'disruptive technology', which can lead to a generation of new diagnostic and therapeutic products, resulting in dramatically improved cancer outcomes. The National Cancer Institute (NCI) of National Institutes of Health explores innovative approaches to multidisciplinary research allowing for a convergence of molecular biology, oncology, physics, chemistry, and engineering and leading to the development of clinically worthy technological approaches. These initiatives include programmatic efforts to enable nanotechnology as a driver of advances in clinical oncology and cancer research, known collectively as the NCI Alliance for Nanotechnology in Cancer (ANC). Over the last 5 years, ANC has demonstrated that multidisciplinary approach catalyzes scientific developments and advances clinical translation in cancer nanotechnology. The research conducted by ANC members has improved diagnostic assays and imaging agents, leading to the development of point-of-care diagnostics, identification and validation of numerous biomarkers for novel diagnostic assays, and the development of multifunctional agents for imaging and therapy. Numerous nanotechnology-based technologies developed by ANC researchers are entering clinical trials. NCI has re-issued ANC program for next 5 years signaling that it continues to have high expectations for cancer nanotechnology's impact on clinical practice. The goals of the next phase will be to broaden access to cancer nanotechnology research through greater clinical translation and outreach to the patient and clinical communities and to support development of entirely new models of cancer care.

Time, Concentration, and pH-Dependent Transport and Uptake of Anthocyanins in a Human Gastric Epithelial (NCI-N87 Cell Line

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Allison A. Atnip

2017-02-01

Full Text Available Anthocyanins are the largest class of water soluble plant pigments and a common part of the human diet. They may have many potential health benefits, including antioxidant, anti-inflammatory, anti-cancer, and cardioprotective activities. However, anthocyanin metabolism is not well understood. Studies suggest that anthocyanins absorption may occur in the stomach, in which the acidic pH favors anthocyanin stability. A gastric epithelial cell line (NCI-N87 has been used to study the behavior of anthocyanins at a pH range of 3.0–7.4. This work examines the effects of time (0–3 h, concentration (50–1500 µM, and pH (3.0, 5.0, 7.4 on the transport and uptake of anthocyanins using NCI-N87 cells. Anthocyanins were transported from the apical to basolateral side of NCI-N87 cells in time and dose dependent manners. Over the treatment time of 3 h the rate of transport increased, especially with higher anthocyanin concentrations. The non-linear rate of transport may suggest an active mechanism for the transport of anthocyanins across the NCI-N87 monolayer. At apical pH 3.0, higher anthocyanin transport was observed compared to pH 5.0 and 7.4. Reduced transport of anthocyanins was found to occur at apical pH 5.0.

NCI designated cancer center funding not influenced by organizational structure.

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Wolfe, Margaret E; Yagoda, Daniel; Thurman, Paul W; Luna, Jorge M; Figg, William Douglas

2009-05-01

National Cancer Institutes (NCI) designated cancer centers use one of three organizational structures. The hypothesis of this study is that there are differences in the amount of annual NCI funding per faculty member based on a cancer center's organizational structure. The study also considers the impact of secondary factors (i.e., the existence of a clinical program, the region and the size of the city in which the cancer center is located) on funding and the number of Howard Hughes Medical Institute (HHMI) investigators at each cancer center. Of the 63 cancer centers, 44 use a matrix structure, 16 have a freestanding structure, and three have a Department of Oncology structure. Kruskal-Wallis tests reveal no statistically significant differences in the amount of funding per faculty member or the number of HHMI investigators between centers with a matrix, freestanding or Department of Oncology structure. Online research and telephone interviews with each cancer center were used to gather information, including: organizational structure, the presence of a clinical program, the number of faculty members, and the number of Howard Hughes Medical Institute investigators. Statistical tests were used to assess the impact which organizational structure has on the amount of funding per faculty member and number of HHMI investigators. While the results seem to suggest that the organizational structure of a given cancer center does not impact the amount of NCI funding or number of HHMI investigators which it attracts, the existence of this relationship is likely masked by the small sample size in this study. Further studies may be appropriate to examine the effect organizational structure has on other measurements which are relevant to cancer centers, such as quality and quantity of research produced.

Inhibition of Calcium-Activated Chloride Channel ANO1/TMEM16A Suppresses Tumor Growth and Invasion in Human Lung Cancer.

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Linghan Jia

Full Text Available Lung cancer or pulmonary carcinoma is primarily derived from epithelial cells that are thin and line on the alveolar surfaces of the lung for gas exchange. ANO1/TMEM16A, initially identified from airway epithelial cells, is a member of Ca2+-activated Cl- channels (CaCCs that function to regulate epithelial secretion and cell volume for maintenance of ion and tissue homeostasis. ANO1/TMEM16A has recently been shown to be highly expressed in several epithelium originated carcinomas. However, the role of ANO1 in lung cancer remains unknown. In this study, we show that inhibition of calcium-activated chloride channel ANO1/TMEM16A suppresses tumor growth and invasion in human lung cancer. ANO1 is upregulated in different human lung cancer cell lines. Knocking-down ANO1 by small hairpin RNAs inhibited proliferation, migration and invasion of GLC82 and NCI-H520 cancel cells evaluated by CCK-8, would-healing, transwell and 3D soft agar assays. ANO1 protein is overexpressed in 77.3% cases of human lung adenocarcinoma tissues detected by immunohistochemistry. Furthermore, the tumor growth in nude mice implanted with GLC82 cells was significantly suppressed by ANO1 silencing. Taken together, our findings provide evidence that ANO1 overexpression contributes to tumor growth and invasion of lung cancer; and suppressing ANO1 overexpression may have therapeutic potential in lung cancer therapy.

A Human Antibody That Binds to the Sixth Ig-Like Domain of VCAM-1 Blocks Lung Cancer Cell Migration In Vitro

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Mi Ra Kim

2017-03-01

Full Text Available Vascular cell adhesion molecule-1 (VCAM-1 is closely associated with tumor progression and metastasis. However, the relevance and role of VCAM-1 in lung cancer have not been clearly elucidated. In this study, we found that VCAM-1 was highly overexpressed in lung cancer tissue compared with that of normal lung tissue, and high VCAM-1 expression correlated with poor survival in lung cancer patients. VCAM-1 knockdown reduced migration of A549 human lung cancer cells into Matrigel, and competitive blocking experiments targeting the Ig-like domain 6 of VCAM-1 (VCAM-1-D6 demonstrated that the VCAM-1-D6 domain was critical for VCAM-1 mediated A549 cell migration into Matrigel. Next, we developed a human monoclonal antibody specific to human and mouse VCAM-1-D6 (VCAM-1-D6 huMab, which was isolated from a human synthetic antibody library using phage display technology. Finally, we showed that VCAM-1-D6 huMab had a nanomolar affinity for VCAM-1-D6 and that it potently suppressed the migration of A549 and NCI-H1299 lung cancer cell lines into Matrigel. Taken together, these results suggest that VCAM-1-D6 is a key domain for regulating VCAM-1-mediated lung cancer invasion and that our newly developed VCAM-1-D6 huMab will be a useful tool for inhibiting VCAM-1-expressing lung cancer cell invasion.

Expression of P-gp, MRP, LRP, GST-π and TopoIIα and intrinsic resistance in human lung cancer cell lines.

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Wang, Jiarui; Zhang, Jinhui; Zhang, Lichuan; Zhao, Long; Fan, Sufang; Yang, Zhonghai; Gao, Fei; Kong, Ying; Xiao, Gary Guishan; Wang, Qi

2011-11-01

This study aimed to determine the relationship between the endogenous levels of P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP), lung resistance-related protein (LRP), glutathione-s-transferase-π (GST‑π) and topoisomerase IIα (TopoIIα) and intrinsic drug resistance in four human lung cancer cell lines, SK-MES-1, SPCA-1, NCI-H-460 and NCI-H-446, of different histological types. The expression of P-gp, MRP, LRP, GST-π and TopoIIα was measured by immunofluorescence, Western blotting and RT-PCR. Drug resistance to cisplatin, doxorubicin and VP-16 was determined using MTT assays. The correlation between expression of the resistance-related proteins and their roles in the resistance to drugs in these cancer cell lines was analyzed. We found that the endogenous levels of P-gp, MRP, LRP, GST-π and TopoIIα in the four cell lines varied. The level of GST-π in the SK-MES-1 cells was the highest, whereas the level of P-gp in the SPCA-1 cells was the lowest. The chemoresistance to cisplatin, doxorubicin and VP-16 in the four cell lines was different. The SPCA-1 cell line was most resistance to cisplatin; SK-MES-1 was most resistance to VP-16; whereas SK-MES-1 was most sensitive to doxorubicin. There was a positive correlation between GST-π expression and resistance to cisplatin, between TopoIIα expression and resistance to VP-16; and a negative correlation was noted between TopoIIα expression and resistance to doxorubicin. In summary, the endogenous expression of P-gp, MRP, LRP, GST-π and TopoIIα was different in the four human lung cancer cell lines of different histological types, and this variance may be associated with the variation in chemosensitivity to cisplatin, doxorubicin and VP-16. Among the related proteins, GST-π may be useful for the prediction of the intrinsic resistance to cisplatin, whereas TopoIIα may be useful to predict resistance to doxorubicin and VP-16 in human lung cancer cell lines.

Effect of primarily cultured human lung cancer-associated fibroblasts on radiosensitivity of lung cancer cells

International Nuclear Information System (INIS)

Ji Xiaoqin; Ji Jiang; Chen Yongbing; Shan Fang; Lu Xueguan

2014-01-01

Objective: To investigate the effect of human lung cancer-associated fibroblasts (CAF) on the radiosensitivity of lung cancer cells when CAF is placed in direct contact co-culture with lung cancer cells. Methods: Human lung CAF was obtained from fresh human lung adenocarcinoma tissue specimens by primary culture and subculture and was then identified by immunofluorescence staining. The CAF was placed in direct contact co-culture with lung cancer A 549 and H 1299 cells, and the effects of CAF on the radiosensitivity of A 549 and H 1299 cells were evaluated by colony-forming assay. Results: The human lung CAF obtained by adherent culture could stably grow and proliferate, and it had specific expression of α-smooth muscle actin, vimentin, and fibroblast activation protein,but without expression of cytokeratin-18. The plating efficiency (PE, %) of A 549 cells at 0 Gy irradiation was (20.0 ± 3.9)% when cultured alone versus (32.3 ± 5.5)% when co-cultured with CAF (t=3.16, P<0.05), and the PE of H 1299 cells at 0 Gy irradiation was (20.6 ± 3.1)% when cultured alone versus (35.2 ± 2.3)% when co-cultured with CAF (t=6.55, P<0.05). The cell survival rate at 2 Gy irradiation (SF 2 ) of A 549 cells was 0.727 ±0.061 when cultured alone versus 0.782 ± 0.089 when co-cultured with CAF (t=0.88, P>0.05), and the SF 2 of H 1299 cells was 0.692 ±0.065 when cultured alone versus 0.782 ± 0.037 when co-cultured with CAF (t=2.08, P>0.05). The protection enhancement ratios of human lung CAF for A 549 cells and H 1299 cells were 1.29 and 1.25, respectively. Conclusions: Human lung CAF reduces the radiosensitivity of lung cancer cells when placed in direct contact co-culture with them, and the radioprotective effect may be attributed to CAF promoting the proliferation of lung cancer cells. (authors)

Association of well-characterized lung cancer lncRNA polymorphisms with lung cancer susceptibility and platinum-based chemotherapy response.

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Gong, Wei-Jing; Yin, Ji-Ye; Li, Xiang-Ping; Fang, Chao; Xiao, Di; Zhang, Wei; Zhou, Hong-Hao; Li, Xi; Liu, Zhao-Qian

2016-06-01

Long non-coding RNAs (lncRNAs) play important roles in carcinogenesis and drug efficacy. Platinum-based chemotherapy is first-line treatment for lung cancer chemotherapy. In this study, we aimed to investigate the association of well-characterized lung cancer lncRNA genetic polymorphisms with the lung cancer susceptibility and platinum-based chemotherapy response. A total of 498 lung cancer patients and 213 healthy controls were recruited in the study. Among them, 467 patients received at least two cycles of platinum-based chemotherapy. Thirteen polymorphisms in HOXA distal transcript antisense RNA (HOTTIP), HOX transcript antisense intergenic RNA (HOTAIR), H19, CDKN2B antisense RNA 1 (ANRIL), colon cancer-associated transcript 2 (CCAT2), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), and maternally expressed gene 3 (MEG3) genes were genotyped by allele-specific MALDI-TOF mass spectrometry. We found that patients with HOTTIP rs5883064 C allele or rs1859168 A allele had increased lung cancer risk (P = 0.01, P = 0.01, respectively). CCAT2 rs6983267 (P = 0.02, adenocarcinoma) and H19 rs2107425 (P = 0.02, age under 50 years) showed strong relationship with lung cancer susceptibility. CCAT2 rs6983267, H19 rs2839698, MALAT1 rs619586, and HOTAIR rs7958904 were associated with platinum-based chemotherapy response in dominant model ((P = 0.02, P = 0.04, P = 0.04, P = 0.01, respectively). ANRIL rs10120688 (P = 0.02, adenocarcinoma) and rs1333049 (P = 0.04, small-cell lung cancer), H19 rs2107425 (P = 0.02, small-cell lung cancer) and HOTAIR rs1899663 (P = 0.03, male; P = 0.03, smoker) were associated with response to platinum-based chemotherapy. HOTTIP, CCAT2, H19, HOTAIR, MALATI, ANRIL genetic polymorphisms were significantly associated with lung cancer susceptibility or platinum-based chemotherapy response. They may be potential clinical biomarkers to predict lung cancer risk and platinum

Expression of hPNAS-4 Radiosensitizes Lewis Lung Cancer

International Nuclear Information System (INIS)

Zeng Hui; Yuan Zhu; Zhu Hong; Li Lei; Shi Huashan; Wang Zi; Fan Yu; Deng Qian; Zeng Jianshuang; He Yinbo; Xiao Jianghong; Li Zhiping

2012-01-01

Purpose: This study aimed to transfer the hPNAS-4 gene, a novel apoptosis-related human gene, into Lewis lung cancer (LL2) and observe its radiosensitive effect on radiation therapy in vitro and in vivo. Methods and Materials: The hPNAS-4 gene was transfected into LL2 cells, and its expression was detected via western blot. Colony formation assay and flow cytometry were used to detect the growth and apoptosis of cells treated with irradiation/PNAS-4 in vitro. The hPNAS-4 gene was transferred into LL2-bearing mice through tail vein injection of the liposome/gene complex. The tumor volumes were recorded after radiation therapy. Proliferating cell nuclear antigen (PCNA) immunohistochemistry staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay were performed to detect the tumor cell growth and apoptosis in vivo. Results: The hPNAS-4 gene was successfully transferred into LL2 cells and tumor tissue, and its overexpressions were confirmed via western blot analysis. Compared with the control, empty plasmid, hPNAS-4, radiation, and empty plasmid plus radiation groups, the hPNAS-4 plus radiation group more significantly inhibited growth and enhanced apoptosis of LL2 cells in vitro and in vivo (P<.05). Conclusions: The hPNAS-4 gene was successfully transferred into LL2 cells and tumor tissue and was expressed in both LL2 cell and tumor tissue. The hPNAS-4 gene therapy significantly enhanced growth inhibition and apoptosis of LL2 tumor cells by radiation therapy in vitro and in vivo. Therefore, it may be a potential radiosensitive treatment of radiation therapy for lung cancer.

The Mechanism of Gefitinib Resistance Induced by Hepatocyte Growth Factor 
in Sensitive Non-small Cell Lung Cancer Cells in Vitro

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Xianglan XUAN

2013-01-01

Full Text Available Background and objective Previous studies have reported that Met might be related to gefitinib resistance in non-small cell lung cancer (NSCLC. The present study aims to explore the mechanism of hepatocyte growth factor (HGF-induced gefitinib resistance in different gene types of sensitive NSCLC in vitro. Methods The PC-9 and H292 cell lines were chosen and induced by HGF. The cell survival was measured using MTT assay, the cell cycle distribution was measured using PI assay, and cell apoptosis with an Annexin V-PE assay, respectively. The c-Met and p-Met protein expression was determined via Western blot analysis. Results Gefitinib inhibited the growth of PC-9 and H292 cells in a dose-dependent manner. The concentration-survival curves of both cell lines shifted to the right when induced with HGF. HGF did not affect PC-9 and H292 cell proliferation. The cell also had a higher cell survival rate when treated with HGF and gefitinib compared with that under gefitinib alone (P<0.05. The apoptotic rate and cell cycle progression showed no significant difference between the HG and G group (P>0.05. HGF stimulated Met phosphorylation in the PC-9 and H292 cells. Gefitinib inhibited the HGF-induced Met phosphorylation in PC-9 cells, but not in H292 cells. Conclusion HGF induces gefitinib resistance in PC-9 and H292 cells. HGF-induced Met phosphorylation may be an important mechanism of gefitinib resistance in sensitive NSCLC.

Mangosenone F, A Furanoxanthone from Garciana mangostana, Induces Reactive Oxygen Species-Mediated Apoptosis in Lung Cancer Cells and Decreases Xenograft Tumor Growth.

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Seo, Kyung Hye; Ryu, Hyung Won; Park, Mi Jin; Park, Ki Hun; Kim, Jin Hyo; Lee, Mi-Ja; Kang, Hyeon Jung; Kim, Sun Lim; Lee, Jin Hwan; Seo, Woo Duck

2015-11-01

Mangosenone F (MSF), a natural xanthone, was isolated form Carcinia mangotana, and a few studies have reported its glycosidase inhibitor effect. In this study we investigated the anti lung cancer effect of MSF both in vitro and in vivo. MSF inhibited cancer cell cytotoxicity and induced and induced apoptosis via reactive oxygen species (ROS) generation in NCI-H460. MSF treatment also showed in pronounced release of apoptogenic cytochrome c from the mitochondria to the cytosol, downregulation of Bcl-2 and Bcl-xL, and upregulation of Bax, suggesting that caspase-mediated pathways were involved in MSF-induced apoptosis. ROS activation of the mitogen-activated protein kinase signaling pathway was shown to play a predominant role in the apoptosis mechanism of MSF. Compared with cisplatin treatment, MSF treatment showed significantly increased inhibition of the growth of NCI-H460 cells xenografted in nude mice. Together, these results indicate the potential of MSF as a candidate natural anticancer drug by promoting ROS production. Copyright © 2015 John Wiley & Sons, Ltd.

Highlights of recent developments and trends in cancer nanotechnology research--view from NCI Alliance for Nanotechnology in Cancer.

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Hull, L C; Farrell, D; Grodzinski, P

2014-01-01

Although the incidence of cancer and cancer related deaths in the United States has decreased over the past two decades due to improvements in early detection and treatment, cancer still is responsible for a quarter of the deaths in this country. There is much room for improvement on the standard treatments currently available and the National Cancer Institute (NCI) has recognized the potential for nanotechnology and nanomaterials in this area. The NCI Alliance for Nanotechnology in Cancer was formed in 2004 to support multidisciplinary researchers in the application of nanotechnology to cancer diagnosis and treatment. The researchers in the Alliance have been productive in generating innovative solutions to some of the central issues of cancer treatment including how to detect tumors earlier, how to target cancer cells specifically, and how to improve the therapeutic index of existing chemotherapies and radiotherapy treatments. Highly creative ideas are being pursued where novelty in nanomaterial development enables new modalities of detection or therapy. This review highlights some of the innovative materials approaches being pursued by researchers funded by the NCI Alliance. Their discoveries to improve the functionality of nanoparticles for medical applications includes the generation of new platforms, improvements in the manufacturing of nanoparticles and determining the underlying reasons for the movement of nanoparticles in the blood. © 2013.

Induction of reactive oxygen species-stimulated distinctive autophagy by chelerythrine in non-small cell lung cancer cells.

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Tang, Zheng-Hai; Cao, Wen-Xiang; Wang, Zhao-Yu; Lu, Jia-Hong; Liu, Bo; Chen, Xiuping; Lu, Jin-Jian

2017-08-01

Chelerythrine (CHE), a natural benzo[c]phenanthridine alkaloid, shows anti-cancer effect through a number of mechanisms. Herein, the effect and mechanism of the CHE-induced autophagy, a type II programmed cell death, in non-small cell lung cancer (NSCLC) cells were studied for the first time. CHE induced cell viability decrease, colony formation inhibition, and apoptosis in a concentration-dependent manner in NSCLC A549 and NCI-H1299 cells. In addition, CHE triggered the expression of phosphatidylethanolamine-modified microtubule-associated protein light-chain 3 (LC3-II). The CHE-induced expression of LC3-II was further increased in the combination treatment with chloroquine (CQ), an autophagy inhibitor, and large amounts of red-puncta were observed in the CHE-treated A549 cells with stable expression of mRFP-EGFP-LC3, indicating that CHE induces autophagy flux. Silence of beclin 1 reversed the CHE-induced expression of LC3-II. Inhibition of autophagy remarkably reversed the CHE-induced cell viability decrease and apoptosis in NCI-H1299 cells but not in A549 cells. Furthermore, CHE triggered reactive oxygen species (ROS) generation in both cell lines. A decreased level of ROS through pretreatment with N-acetyl-L-cysteine reversed the CHE-induced cell viability decrease, apoptosis, and autophagy. Taken together, CHE induced distinctive autophagy in A549 (accompanied autophagy) and NCI-H1299 (pro-death autophagy) cells and a decreased level of ROS reversed the effect of CHE in NSCLC cells in terms of cell viability, apoptosis, and autophagy. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Radiation response of human lung cancer cells with inherent and acquired resistance to cisplatin

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Twentyman, P.R.; Wright, K.A.; Rhodes, T.

1991-01-01

We have derived sublines of three human lung cancer cell lines with acquired resistance to cisplatin. The cisplatin resistant sublines of NCI-H69 (small cell), COR-L23 (large cell), and MOR (adenocarcinoma) show 5.3 fold, 3.1 fold, and 3.8 fold resistance, respectively, determined in a 6-day MTT assay. Although the parent lines show a wide range of glutathione content per cell, the sublines each show similar values to their corresponding parent line. Radiation response curves have been obtained using a soft agar clonogenic assay. Values obtained for the parent lines (95% CL in parentheses) were: NCI-H69: Do = 0.99 Gy (0.87-1.16), n = 2.9 (1.6-5.2), GSH = 14 ng/10(4) cells; COR-L23: Do = 1.23 Gy (1.05-1.49), n = 1.3 (0.7-2.2), GSH = 47 ng/10(4) cells; MOR: Do = 1.66 Gy (1.48-1.88), n = 3.0 (1.9-4.8), GSH = 86 ng/10(4) cells. The cisplatin resistant variants of NCI-H69 and COR-L23 showed 31% and 63% increases, respectively, in Do compared to their parent lines, whereas no change in radiation response was seen in MOR. In this panel of lines, therefore, although there is a correlation between glutathione content and radiosensitivity of the parent cell lines, acquired resistance to cisplatin is not accompanied by increased glutathione content. However, two of the three cisplatin resistant lines do show a significantly reduced radiosensitivity

Phoyunnanin E inhibits migration of non-small cell lung cancer cells via suppression of epithelial-to-mesenchymal transition and integrin αv and integrin β3.

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Petpiroon, Nareerat; Sritularak, Boonchoo; Chanvorachote, Pithi

2017-12-29

The conversion of the epithelial phenotype of cancer cells into cells with a mesenchymal phenotype-so-called epithelial-mesenchymal transition (EMT)-has been shown to enhance the capacity of the cells to disseminate throughout the body. EMT is therefore becoming a potential target for anti-cancer drug discovery. Here, we showed that phoyunnanin E, a compound isolated from Dendrobium venustum, possesses anti-migration activity and addressed its mechanism of action. The cytotoxic and proliferative effects of phoyunnanin E on human non-small cell lung cancer-derived H460, H292, and A549 cells and human keratinocyte HaCaT cells were investigated by MTT assay. The effect of phoyunnanin E on EMT was evaluated by determining the colony formation and EMT markers. The migration and invasion of H460, H292, A549 and HaCaT cells was evaluated by wound healing assay and transwell invasion assay, respectively. EMT markers, integrins and migration-associated proteins were examined by western blot analysis. Phoyunnanin E at the concentrations of 5 and 10 μM, which are non-toxic to H460, H292, A549 and HaCaT cells showed good potential to inhibit the migratory activity of three types of human lung cancer cells. The anti-migration effect of phoyunnanin E was shown to relate to the suppressed EMT phenotypes, including growth in anchorage-independent condition, cell motility, and EMT-specific protein markers (N-cadherin, vimentin, slug, and snail). In addition to EMT suppression, we found that phoyunnanin E treatment with 5 and 10 μM could decrease the cellular level of integrin αv and integrin β3, these integrins are frequently up-regulated in highly metastatic tumor cells. We further characterized the regulatory proteins in cell migration and found that the cells treated with phoyunnanin E exhibited a significantly lower level of phosphorylated focal adhesion kinase (p-FAK) and phosphorylated ATP-dependent tyrosine kinase (p-AKT), and their downstream effectors (including

Helicobacter pylori seropositivity and risk of lung cancer.

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Jill Koshiol

Full Text Available Lung cancer is the leading cause of cancer mortality worldwide. Helicobacter pylori (H. pylori is a risk factor for distal stomach cancer, and a few small studies have suggested that H. pylori may be a potential risk factor for lung cancer. To test this hypothesis, we conducted a study of 350 lung adenocarcinoma cases, 350 squamous cell carcinoma cases, and 700 controls nested within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC cohort of male Finnish smokers. Controls were one-to-one matched by age and date of baseline serum draw. Using enzyme-linked immunosorbent assays to detect immunoglobulin G antibodies against H. pylori whole-cell and cytotoxin-associated gene (CagA antigens, we calculated odds ratios (ORs and 95% confidence intervals (95% CIs for associations between H. pylori seropositivity and lung cancer risk using conditional logistic regression. H. pylori seropositivity was detected in 79.7% of cases and 78.5% of controls. After adjusting for pack-years and cigarettes smoked per day, H. pylori seropositivity was not associated with either adenocarcinoma (OR: 1.1, 95% CI: 0.75-1.6 or squamous cell carcinoma (OR: 1.1, 95% CI: 0.77-1.7. Results were similar for CagA-negative and CagA-positive H. pylori seropositivity. Despite earlier small studies suggesting that H. pylori may contribute to lung carcinogenesis, H. pylori seropositivity does not appear to be associated with lung cancer.

Decreased glucose uptake by hyperglycemia is regulated by different mechanisms in human cancer cells and monocytes

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Kim, Chae Kyun; Chung, June Key; Lee, Yong Jin; Hong, Mee Kyoung; Jeong, Jae Min; Lee, Dong Soo; Lee, Myung Chul

2002-01-01

To clarify the difference in glucose uptake between human cancer cells and monocytes, we studied ( 18 F) fluorodeoxyglucose (FDG) uptake in three human colon cancer cell lines (SNU-C2A, SNU-C4, SNU-C5), one human lung cancer cell line (NCI-H522), and human peripheral blood monocytes. The FDG uptake of both cancer cells and monocytes was increased in glucose-free medium, but decreased in the medium containing 16.7 mM glucose (hyperglycemic). The level of Glut1 mRNA decreased in human colon cancer cells and NCI-H522 under hyperglycemic condition. Glut1 protein expression was also decreased in the four human cancer cell lines under hyperglycemic condition, whereas it was consistently undetectable in monocytes. SNU-C2A, SNU-C4 and NCI-H522 showed a similar level of hexokinase activity (7.5-10.8 mU/mg), while SNU-C5 and moncytes showed lower range of hexokinase activity (4.3-6.5 mU/mg). These data suggest that glucose uptake is regulated by different mechanisms in human cancer cells and monocytes

Lung cancer

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Aisner, J.

1985-01-01

This book contains 13 chapters. Some of the chapter titles are: The Pathology of Lung Cancer; Radiotherapy for Non-Small-Cell Cancer of the Lung; Chemotherapy for Non-Small-Cell Lung Cancer; Immunotherapy in the Management of Lung Cancer; Preoperative Staging and Surgery for Non-Small-Cell Lung Cancer; and Prognostic Factors in Lung Cancer

Differential Serum Cytokine Levels and Risk of Lung Cancer between African and European Americans

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Pine, Sharon R.; Mechanic, Leah E.; Enewold, Lindsey; Bowman, Elise D.; Ryan, Bríd M.; Cote, Michele L.; Wenzlaff, Angela S.; Loffredo, Christopher A.; Olivo-Marston, Susan; Chaturvedi, Anil; Caporaso, Neil E.; Schwartz, Ann G.; Harris, Curtis C.

2015-01-01

Background African Americans have a higher risk of developing lung cancer than European Americans. Previous studies suggested that certain circulating cytokines were associated with lung cancer. We hypothesized that variations in serum cytokine levels exist between African Americans and European Americans, and increased circulating cytokine levels contribute to lung cancer differently in the two races. Methods Differences in ten serum cytokine levels, interleukin (IL)-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, granulocyte macrophage colony-stimulating factor (GMCSF), interferon (IFN)-γ and tumor necrosis factor (TNF)-α between 170 African-American and 296 European-American controls from the National Cancer Institute-Maryland (NCI-MD) case-control study were assessed. Associations of the serum cytokine levels with lung cancer were analyzed. Statistically significant results were replicated in the prospective Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial and the Wayne State University (WSU) Karmanos Cancer Institute case-control study. Results Six cytokines: IL-4, IL-5, IL-8, IL-10, IFNγ, and TNFα, were significantly higher among European-American as compared to African-American controls. Elevated IL-6 and IL-8 levels were associated with lung cancer among both races in all three studies. Elevated IL-1β, IL-10 and TNFα levels were associated with lung cancer only among African Americans. The association between elevated TNFα levels and lung cancer among European Americans was significant after adjustment for additional factors. Conclusions Serum cytokine levels vary by race and might contribute to lung cancer differently between African Americans and European Americans. Impact Future work examining risk prediction models of lung cancer can measure circulating cytokines to accurately characterize risk within racial groups. PMID:26711330

Pentastatin-1, a collagen IV derived 20-mer peptide, suppresses tumor growth in a small cell lung cancer xenograft model.

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Koskimaki, Jacob E; Karagiannis, Emmanouil D; Tang, Benjamin C; Hammers, Hans; Watkins, D Neil; Pili, Roberto; Popel, Aleksander S

2010-02-01

Angiogenesis is the formation of neovasculature from a pre-existing vascular network. Progression of solid tumors including lung cancer is angiogenesis-dependent. We previously introduced a bioinformatics-based methodology to identify endogenous anti-angiogenic peptide sequences, and validated these predictions in vitro in human umbilical vein endothelial cell (HUVEC) proliferation and migration assays. One family of peptides with high activity is derived from the alpha-fibrils of type IV collagen. Based on the results from the in vitro screening, we have evaluated the ability of a 20 amino acid peptide derived from the alpha5 fibril of type IV collagen, pentastatin-1, to suppress vessel growth in an angioreactor-based directed in vivo angiogenesis assay (DIVAA). In addition, pentastatin-1 suppressed tumor growth with intraperitoneal peptide administration in a small cell lung cancer (SCLC) xenograft model in nude mice using the NCI-H82 human cancer cell line. Pentastatin-1 decreased the invasion of vessels into angioreactors in vivo in a dose dependent manner. The peptide also decreased the rate of tumor growth and microvascular density in vivo in a small cell lung cancer xenograft model. The peptide treatment significantly decreased the invasion of microvessels in angioreactors and the rate of tumor growth in the xenograft model, indicating potential treatment for angiogenesis-dependent disease, and for translational development as a therapeutic agent for lung cancer.

Pentastatin-1, a collagen IV derived 20-mer peptide, suppresses tumor growth in a small cell lung cancer xenograft model

International Nuclear Information System (INIS)

Koskimaki, Jacob E; Karagiannis, Emmanouil D; Tang, Benjamin C; Hammers, Hans; Watkins, D Neil; Pili, Roberto; Popel, Aleksander S

2010-01-01

Angiogenesis is the formation of neovasculature from a pre-existing vascular network. Progression of solid tumors including lung cancer is angiogenesis-dependent. We previously introduced a bioinformatics-based methodology to identify endogenous anti-angiogenic peptide sequences, and validated these predictions in vitro in human umbilical vein endothelial cell (HUVEC) proliferation and migration assays. One family of peptides with high activity is derived from the α-fibrils of type IV collagen. Based on the results from the in vitro screening, we have evaluated the ability of a 20 amino acid peptide derived from the α5 fibril of type IV collagen, pentastatin-1, to suppress vessel growth in an angioreactor-based directed in vivo angiogenesis assay (DIVAA). In addition, pentastatin-1 suppressed tumor growth with intraperitoneal peptide administration in a small cell lung cancer (SCLC) xenograft model in nude mice using the NCI-H82 human cancer cell line. Pentastatin-1 decreased the invasion of vessels into angioreactors in vivo in a dose dependent manner. The peptide also decreased the rate of tumor growth and microvascular density in vivo in a small cell lung cancer xenograft model. The peptide treatment significantly decreased the invasion of microvessels in angioreactors and the rate of tumor growth in the xenograft model, indicating potential treatment for angiogenesis-dependent disease, and for translational development as a therapeutic agent for lung cancer

The national cancer institute (NCI) and cancer biology in a 'post genome world'

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Klausner, Richard D.

1996-01-01

The National Cancer Institute (NCI) exists to reduce the burden of all cancers through research and discovery. Extensive restructuring of the NCI over the past year has been aimed at assuring that the institution functions in all ways to promote opportunities for discovery in the laboratory, in the clinic, and in the community. To do this well requires the difficult and almost paradoxical problem of planning for scientific discovery which, in turn is based on the freedom to pursue the unanticipated. The intellectual and structural landscape of science is changing and it places new challenges, new demands and new opportunities for facilitating discovery. The nature of cancer as a disease of genomic instability and of accumulated genetic change, coupled with a possibility of the development of new technologies for reading, utilizing, interpreting and manipulating the genome of single cells, provides unprecedented opportunities for a new type of high through-put biology that will change the nature of discovery, cancer detection, diagnosis, prognosis, therapeutic decision-making and therapeutic discovery. To capture these new opportunities will require attention to be paid to integrate the development of technology and new scientific discoveries with the ability to apply advances rapidly and efficiently through clinical trials

NCI Visuals Online

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NCI Visuals Online contains images from the collections of the National Cancer Institute's Office of Communications and Public Liaison, including general biomedical and science-related images, cancer-specific scientific and patient care-related images, and portraits of directors and staff of the National Cancer Institute.

Program Spotlight: Ground Broken for NCI-supported Cancer Treatment Center in Puerto Rico

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Dr. Sanya A. Springfield represented NCI at the groundbreaking ceremonies for the University of Puerto Rico (UPR) cancer hospital. In her remarks, she acknowledged the driving force behind this development is the UPR and the MD Anderson Cancer Center partnership.

Hypoxia-Induced Cisplatin Resistance in Non-Small Cell Lung Cancer Cells Is Mediated by HIF-1α and Mutant p53 and Can Be Overcome by Induction of Oxidative Stress.

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Deben, Christophe; Deschoolmeester, Vanessa; De Waele, Jorrit; Jacobs, Julie; Van den Bossche, Jolien; Wouters, An; Peeters, Marc; Rolfo, Christian; Smits, Evelien; Lardon, Filip; Pauwels, Patrick

2018-04-21

The compound APR-246 (PRIMA-1 MET ) is a known reactivator of (mutant) p53 and inducer of oxidative stress which can sensitize cancer cells to platinum-based chemotherapeutics. However, the effect of a hypoxic tumor environment has been largely overlooked in this interaction. This study focusses on the role of hypoxia-inducible factor-1α (HIF-1α) and the p53 tumor suppressor protein in hypoxia-induced cisplatin resistance in non-small cell lung cancer (NSCLC) cells and the potential of APR-246 to overcome this resistance. We observed that hypoxia-induced cisplatin resistance only occurred in the p53 mutant NCI-H2228 Q331 * cell line, and not in the wild type A549 and mutant NCI-H1975 R273H cell lines. Cisplatin reduced HIF-1α protein levels in NCI-H2228 Q331 * cells, leading to a shift in expression from HIF-1α-dependent to p53-dependent transcription targets under hypoxia. APR-246 was able to overcome hypoxia-induced cisplatin resistance in NCI-H2228 Q331 * cells in a synergistic manner without affecting mutant p53 Q331 * transcriptional activity, but significantly depleting total glutathione levels more efficiently under hypoxic conditions. Synergism was dependent on the presence of mutant p53 Q331 * and the induction of reactive oxygen species, with depletion of one or the other leading to loss of synergism. Our data further support the rationale of combining APR-246 with cisplatin in NSCLC, since their synergistic interaction is retained or enforced under hypoxic conditions in the presence of mutant p53.

Hypoxia-Induced Cisplatin Resistance in Non-Small Cell Lung Cancer Cells Is Mediated by HIF-1α and Mutant p53 and Can Be Overcome by Induction of Oxidative Stress

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Christophe Deben

2018-04-01

Full Text Available The compound APR-246 (PRIMA-1MET is a known reactivator of (mutant p53 and inducer of oxidative stress which can sensitize cancer cells to platinum-based chemotherapeutics. However, the effect of a hypoxic tumor environment has been largely overlooked in this interaction. This study focusses on the role of hypoxia-inducible factor-1α (HIF-1α and the p53 tumor suppressor protein in hypoxia-induced cisplatin resistance in non-small cell lung cancer (NSCLC cells and the potential of APR-246 to overcome this resistance. We observed that hypoxia-induced cisplatin resistance only occurred in the p53 mutant NCI-H2228Q331* cell line, and not in the wild type A549 and mutant NCI-H1975R273H cell lines. Cisplatin reduced HIF-1α protein levels in NCI-H2228Q331* cells, leading to a shift in expression from HIF-1α-dependent to p53-dependent transcription targets under hypoxia. APR-246 was able to overcome hypoxia-induced cisplatin resistance in NCI-H2228Q331* cells in a synergistic manner without affecting mutant p53Q331* transcriptional activity, but significantly depleting total glutathione levels more efficiently under hypoxic conditions. Synergism was dependent on the presence of mutant p53Q331* and the induction of reactive oxygen species, with depletion of one or the other leading to loss of synergism. Our data further support the rationale of combining APR-246 with cisplatin in NSCLC, since their synergistic interaction is retained or enforced under hypoxic conditions in the presence of mutant p53.

Decreased glucose uptake by hyperglycemia is regulated by different mechanisms in human cancer cells and monocytes

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Kim, Chae Kyun; Chung, June Key; Lee, Yong Jin; Hong, Mee Kyoung; Jeong, Jae Min; Lee, Dong Soo; Lee, Myung Chul [College of Medicine, Seoul National Univ., Seoul (Korea, Republic of)

2002-04-01

To clarify the difference in glucose uptake between human cancer cells and monocytes, we studied ({sup 18}F) fluorodeoxyglucose (FDG) uptake in three human colon cancer cell lines (SNU-C2A, SNU-C4, SNU-C5), one human lung cancer cell line (NCI-H522), and human peripheral blood monocytes. The FDG uptake of both cancer cells and monocytes was increased in glucose-free medium, but decreased in the medium containing 16.7 mM glucose (hyperglycemic). The level of Glut1 mRNA decreased in human colon cancer cells and NCI-H522 under hyperglycemic condition. Glut1 protein expression was also decreased in the four human cancer cell lines under hyperglycemic condition, whereas it was consistently undetectable in monocytes. SNU-C2A, SNU-C4 and NCI-H522 showed a similar level of hexokinase activity (7.5-10.8 mU/mg), while SNU-C5 and moncytes showed lower range of hexokinase activity (4.3-6.5 mU/mg). These data suggest that glucose uptake is regulated by different mechanisms in human cancer cells and monocytes.

Reliability of up-to-date risk factor between residential radon and lung cancer

International Nuclear Information System (INIS)

Tokonami, Shinji; Ishikawa, Tetsuo; Sorimachi, Atsuyuki; Kobayashi, Yosuke; Yoshinaga, Shinji; Quanfu, Sun; Akiba, Suminori

2008-01-01

Full text: The WHO launched an international radon project in January, 2005 because two major scientific articles on the residential-radon-and-lung-cancer risk have been published. Furthermore, the ICRP has just issued a new recommendation (Publ. 103). In the publication, radon issues have been mentioned using these references. They show that there is a significant correlation between radon exposures and lung cancer risks even with a somewhat lower radon concentration than an internationally recommended level (200 Bq m -3 ). In most cases, residential radon concentrations were measured by passive integrating radon monitors based on the alpha track detection techniques in their studies. We examined detection responses for the presence of thoron with some typical alpha track detectors (Kf K: Germany, Radtrak: USA and NRPB: UK), which were widely used in many epidemiological studies. In addition, we measured indoor radon and thoron concentrations in cave dwellings in Gansu Province, China, in which the National Cancer Institute (NCI) conducted a large-scale epidemiological study. The NCI concluded that there was also a significant correlation between the two aforementioned parameters, which was a similar value to recently acceptable one. However, our results on radon concentrations were obviously different from them because there was much thoron in that area. The present study demonstrates whether these risk factors are really correct throughout our data or not. Tokonami (2005) has pointed out that some of popular alpha track detectors are sensitive to thoron ( 220 Rn). This finding implies that radon readings will be overestimated and consequently may lead to biased estimates of lung cancer risk. The present study describes thoron interference on accurate radon measurements from the viewpoint of both experimental studies and field experiences. (author)

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

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Hussein A N Al-Wadei

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

Lung Cancer Prevention

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... Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin Cancer ... following PDQ summaries for more information about lung cancer: Lung Cancer Screening Non-Small Cell Lung Cancer Treatment ...

Lung Cancer Screening

Science.gov (United States)

... factors increase or decrease the risk of lung cancer. Lung cancer is a disease in which malignant (cancer) ... following PDQ summaries for more information about lung cancer: Lung Cancer Prevention Non-Small Cell Lung Cancer Treatment ...

Novel electrospun gelatin/oxycellulose nanofibers as a suitable platform for lung disease modeling

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Švachová, Veronika, E-mail: xcsvachova@fch.vutbr.cz [Institute of Materials Chemistry, Brno University of Technology (Czech Republic); Vojtová, Lucy [CEITEC – Central European Institute of Technology, Brno University of Technology (Czech Republic); SCITEG, a.s., Brno (Czech Republic); Pavliňák, David [Department of Physical Electronics, Masaryk University (Czech Republic); Vojtek, Libor [Institute of Experimental Biology, Masaryk University (Czech Republic); Sedláková, Veronika [Department of Histology and Embryology, Masaryk University (Czech Republic); International Clinical Research, St. Anne' s University Hospital, Brno (Czech Republic); Hyršl, Pavel [Institute of Experimental Biology, Masaryk University (Czech Republic); Alberti, Milan [Department of Physical Electronics, Masaryk University (Czech Republic); Jaroš, Josef; Hampl, Aleš [Department of Histology and Embryology, Masaryk University (Czech Republic); International Clinical Research, St. Anne' s University Hospital, Brno (Czech Republic); Jančář, Josef [Institute of Materials Chemistry, Brno University of Technology (Czech Republic); CEITEC – Central European Institute of Technology, Brno University of Technology (Czech Republic); SCITEG, a.s., Brno (Czech Republic)

2016-10-01

Novel hydrolytically stable gelatin nanofibers modified with sodium or calcium salt of oxycellulose were prepared by electrospinning method. The unique inhibitory effect of these nanofibers against Escherichia coli bacteria was examined by luminometric method. Biocompatibility of these gelatin/oxycellulose nanofibers with eukaryotic cells was tested using human lung adenocarcinoma cell line NCI-H441. Cells firmly adhered to nanofiber surface, as determined by scanning electron microscopy, and no signs of cell dying were detected by fluorescent live/dead assay. We propose that the newly developed gelatin/oxycellulose nanofibers could be used as promising scaffold for lung disease modeling and anti-cancer drug testing. - Highlights: • Novel hydrolytically stable gelatin nanofibers modified with oxycellulose were prepared by electrospinning. • ATR–FTIR spectroscopy and EDX confirmed the presence of oxycellulose in the nanofibers. • Nanofibers modified with calcium salt of oxycellulose exhibited significant antibacterial properties. • Nanofibers modified with sodium salt of oxycellulose revealed excellent biocompatibility with cell line NCI-H441.

Colossolactone H, a new Ganoderma triterpenoid exhibits cytotoxicity and potentiates drug efficacy of gefitinib in lung cancer.

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Chen, Su-Yu; Chang, Chao-Lin; Chen, Teng-Hai; Chang, Ya-Wen; Lin, Shwu-Bin

2016-10-01

Three pentacyclic triterpene dilactones were isolated from the fruiting bodies of Ganoderma colossum, a medicinal mushroom. Colossolactone H (colo H) as a new compound and the most cytotoxic among the isolates was studied for its anticancer mechanism and the potential use in cancer therapy. Gene expression profiling analysis indicated that treatment of lung cancer cells with colo H caused upregulation of 252 genes and downregulation of 398 genes. Gene ontology enrichment analysis indicated that the downregulated genes were the most significantly enriched in cell cycle progression, and the upregulated genes were significantly enriched in metabolic process, cellular response to stimulus, and oxidation reduction. Accordingly, colo H was found to halt cell growth and induce cell apoptosis via the elevation of cellular reactive oxygen species to cause DNA damage and the increase of tumor suppressor p53 protein. These events facilitate additive cytotoxicity of colo H and gefitinib for gefitinib-resistant H1650 lung cancer cells. Furthermore, combination of colo H and gefitinib effectively inhibited the growth of tumor xenografts in athymic mice. In addition to the efficacy in adjunctive cancer therapy, we have also demonstrated the isolation of colo H from cultivated G. colossum. Thus it is feasible to use colo H or Ganoderma colossum for cancer therapy. Copyright © 2016. Published by Elsevier B.V.

The enhancing effect of genistein on apoptosis induced by trichostatin A in lung cancer cells with wild type p53 genes is associated with upregulation of histone acetyltransferase

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Wu, Tzu-Chin [Chest Clinic, Chung Shan Medical University Hospital, Taichung, Taiwan (China); Lin, Yi-Chin [Department of Nutritional Science, Chung Shan Medical University, Taichung, Taiwan (China); Chen, Hsiao-Ling [Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan (China); Huang, Pei-Ru; Liu, Shang-Yu [Department of Nutritional Science, Chung Shan Medical University, Taichung, Taiwan (China); Yeh, Shu-Lan, E-mail: suzyyeh@csmu.edu.tw [Department of Nutritional Science, Chung Shan Medical University, Taichung, Taiwan (China); Department of Nutrition, Chung Shan Medical University Hospital, Taichung, Taiwan (China)

2016-02-01

Genistein has been shown to enhance the antitumor activity of trichostatin A (TSA) in human lung carcinoma A549 cells. However, whether the combined treatment exerts the same effect in other lung cancer cells is unclear. In the present study we first compared the enhancing effect of genistein on the antitumor effect of TSA in ABC-1, NCI-H460 (H460) and A549 cells. Second, we investigated whether the effects of genistein are associated with increased histone/non-histone protein acetylation. We found that the enhancing effect of genistein on cell-growth-arrest in ABC-1 cells (p53 mutant) was less than in A549 and H460 cells. Genistein enhanced TSA induced apoptosis in A549 and H460 cells rather than in ABC-1 cells. After silencing p53 expression in A549 and H460 cells, the enhancing effect of genistein was diminished. In addition, genistein increased TSA-induced histone H3/H4 acetylation in A549 and H460 cells. Genistein also increased p53 acetylation in H460 cells. The inhibitor of acetyltransferase, anacardic acid, diminished the enhancing effect of genistein on all TSA-induced histone/p53 acetylation and apoptosis. Genistein in combination with TSA increased the expression of p300 protein, an acetyltransferase, in A549 and NCI-H460 cells. Furthermore, we demonstrated that genistein also enhanced the antitumor effect of genistein in A549-tumor-bearing mice. Taken together, these results suggest that the enhancing effects of genistein on TSA-induced apoptosis in lung cancer cells were p53-dependent and were associated with histone/non-histone protein acetylation. - Highlights: • Genistein enhances the antitumor effect of TSA through p53-associated pathways. • Genistein enhances TSA-induced histone acetylation commonly. • An acetyltransferase inhibitor diminishes the antitumor effect of genistein + TSA. • TSA in combination with genistein increases the expression of p300. • Genistein given by i.p. injection increases the antitumor effect of TSA in vivo.

The enhancing effect of genistein on apoptosis induced by trichostatin A in lung cancer cells with wild type p53 genes is associated with upregulation of histone acetyltransferase

International Nuclear Information System (INIS)

Wu, Tzu-Chin; Lin, Yi-Chin; Chen, Hsiao-Ling; Huang, Pei-Ru; Liu, Shang-Yu; Yeh, Shu-Lan

2016-01-01

Genistein has been shown to enhance the antitumor activity of trichostatin A (TSA) in human lung carcinoma A549 cells. However, whether the combined treatment exerts the same effect in other lung cancer cells is unclear. In the present study we first compared the enhancing effect of genistein on the antitumor effect of TSA in ABC-1, NCI-H460 (H460) and A549 cells. Second, we investigated whether the effects of genistein are associated with increased histone/non-histone protein acetylation. We found that the enhancing effect of genistein on cell-growth-arrest in ABC-1 cells (p53 mutant) was less than in A549 and H460 cells. Genistein enhanced TSA induced apoptosis in A549 and H460 cells rather than in ABC-1 cells. After silencing p53 expression in A549 and H460 cells, the enhancing effect of genistein was diminished. In addition, genistein increased TSA-induced histone H3/H4 acetylation in A549 and H460 cells. Genistein also increased p53 acetylation in H460 cells. The inhibitor of acetyltransferase, anacardic acid, diminished the enhancing effect of genistein on all TSA-induced histone/p53 acetylation and apoptosis. Genistein in combination with TSA increased the expression of p300 protein, an acetyltransferase, in A549 and NCI-H460 cells. Furthermore, we demonstrated that genistein also enhanced the antitumor effect of genistein in A549-tumor-bearing mice. Taken together, these results suggest that the enhancing effects of genistein on TSA-induced apoptosis in lung cancer cells were p53-dependent and were associated with histone/non-histone protein acetylation. - Highlights: • Genistein enhances the antitumor effect of TSA through p53-associated pathways. • Genistein enhances TSA-induced histone acetylation commonly. • An acetyltransferase inhibitor diminishes the antitumor effect of genistein + TSA. • TSA in combination with genistein increases the expression of p300. • Genistein given by i.p. injection increases the antitumor effect of TSA in vivo.

NCI Requests Cancer Targets for Monoclonal Antibody Production and Characterization | Office of Cancer Clinical Proteomics Research

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In an effort to provide well-characterized monoclonal antibodies to the scientific community, NCI's Antibody Characterization Program requests cancer-related protein targets for affinity production and distribution. Submissions will be accepted through July 11, 2014.

76 FR 14034 - Proposed Collection; Comment Request; NCI Cancer Genetics Services Directory Web-Based...

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2011-03-15

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health Proposed Collection; Comment Request; NCI Cancer Genetics Services Directory Web-Based Application Form and Update Mailer Summary: In... Cancer Genetics Services Directory Web-based Application Form and Update Mailer. [[Page 14035

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

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

2015-07-01

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

Investigation of internalization and cytotoxicity of 125I-[Tyr3]-octreotide in NCI-H446 cell line

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Sun Junjie; Fan Wo; Xu Yujie; Zhang Youjiu; Zhu Ran; Hu Mingjiang

2004-01-01

Objective: To investigate the [Tyr 3 ]-octreotide (TOC) internalizing capacity of NCI-H446 cell line, and the cytotoxicity of 125 I-TOC in NCI-H446 cell line. To assess the therapeutic radiopharmaceutical potentiality of 125 I-TOC for the somatostatin receptor (SSTR) positive tumor. Methods: NCI-H446 cells were incubated together with 125 I-TOC for different periods of time, the amount of internalized 125 I-TOC and the 125 I-TOC bound on the cellular nucleus were detected with γ counter, respectively. The viability of the cells was analyzed by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay at different time points with various doses of 125 I-TOC, free 125 I and TOC. Results: 125 I-TOC was internalized into the nucleus and bound on the nucleus in a time-dependent manner. 125 I-TOC bound on the nucleus increased to the highest level at 24 h, the amount of nucleus bound 125 I-TOC at 24 h was 7 times higher than that at 0.5 h. Cytotoxicity of 125 I-TOC in SSTR positive NCI-H446 cells was also dose- and time-dependent. The supreme effect of cytotoxicity was found at 96 h with 74 kBq 125 I-TOC, the survival ratio of cells was reduced to (44.8 ± 7.2)%. Conclusions: 125 I-TOC can be internalized into SSTR positive cells mediated by SSTR. The NCI-H446 cells can be killed by Auger electron emitting from 125 I-TOC. Effect of cytotoxicity showed dose- and time-dependent

Kidney Cancer Risk Questionnaire

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... NCI Cancer Information A to Z Treatment Roles Cancer Types Bladder Brain/Spine Breast Cervical Colorectal Esophageal Gallbladder Head/Neck Kidney Leukemia Liver Lung Lymphoma Multiple Myeloma Ovarian Pancreatic ...

Nutrition for Lung Cancer

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... Become An Advocate Volunteer Ways To Give Lung Cancer www.lung.org > Lung Health and Diseases > Lung Disease Lookup > ... Cancer Learn About Lung Cancer What Is Lung Cancer Lung Cancer Basics Causes & Risk Factors Lung Cancer Staging ...

Lung Cancer

International Nuclear Information System (INIS)

Maghfoor, Irfan; Perry, M.C.

2005-01-01

Lung cancer is the leading cause of cancer-related mortality. Since tobacco smoking is the cause in vast majority of cases, the incidence of lung cancer is expected to rise in those countries with high or rising incidence of tobacco smoking. Even though population at a risk of developing lung cancer are easily identified, mass screening for lung cancer is not supported by currently available evidence. In case of non-small cell lung cancer, a cure may be possible with surgical resection followed by post-operative chemotherapy in those diagnosed at an early stage. A small minority of patients who present with locally advanced disease may also benefit from preoperative chemotherapy and/or radiation therapy to down stage the tumor to render it potentially operable. In a vast majority of patients, however, lung cancer presents at an advanced stage and a cure is not possible with currently available therapeutic strategies. Similarly small cell lung cancer confined to one hemi-thorax may be curable with a combination of chemotherapy and thoracic irradiation followed by prophylactic cranial irradiation, if complete remission is achieved at the primary site. Small cell lung cancer that is spread beyond the confines of one hemi-thorax is however, considered incurable. In this era of molecular targeted therapies, new agents are constantly undergoing pre-clinical and clinical testing with the aim of targeting the molecular pathways thought to involved in etiology and pathogenesis of lung cancer. (author)

P120-catenin isoforms 1A and 3A differently affect invasion and proliferation of lung cancer cells

International Nuclear Information System (INIS)

Liu Yang; Dong Qianze; Zhao Yue; Dong Xinjun; Miao Yuan; Dai Shundong; Yang Zhiqiang; Zhang Di; Wang Yan; Li Qingchang; Zhao Chen; Wang Enhua

2009-01-01

Different isoforms of p120-catenin (p120ctn), a member of the Armadillo gene family, are variably expressed in different tissues as a result of alternative splicing and the use of multiple translation initiation codons. When expressed in cancer cells, these isoforms may confer different properties with respect to cell adhesion and invasion. We have previously reported that the p120ctn isoforms 1 and 3 were the most highly expressed isoforms in normal lung tissues, and their expression level was reduced in lung tumor cells. To precisely define their biological roles, we transfected p120ctn isoforms 1A and 3A into the lung cancer cell lines A549 and NCI-H460. Enhanced expression of p120ctn isoform 1A not only upregulated E-cadherin and β-catenin, but also downregulated the Rac1 activity, and as a result, inhibited the ability of cells to invade. In contrast, overexpression of p120ctn isoform 3A led to the inactivation of Cdc42 and the activation of RhoA, and had a smaller influence on invasion. However, we found that isoform 3A had a greater ability than isoform 1A in both inhibiting the cell cycle and reducing tumor cell proliferation. The present study revealed that p120ctn isoforms 1A and 3A differently regulated the adhesive, proliferative, and invasive properties of lung cancer cells through distinct mechanisms

Puerto Rico NCI Community Oncology Research Program Minority/Underserved | Division of Cancer Prevention

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The Puerto Rico NCI Community Oncology Research Program (PRNCORP) will be the principal organization in the island that promotes cancer prevention, control and screening/post-treatment surveillance clinical trials. It will conduct cancer care delivery research and will provide access to treatment and imaging clinical trials conducted under the reorganization of the National

Dithiolethione modified valproate and diclofenac increase E-cadherin expression and decrease proliferation of non-small cell lung cancer cells.

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Moody, Terry W; Switzer, Christopher; Santana-Flores, Wilmarie; Ridnour, Lisa A; Berna, Marc; Thill, Michelle; Jensen, Robert T; Sparatore, Anna; Del Soldato, Piero; Yeh, Grace C; Roberts, David D; Giaccone, Giuseppe; Wink, David A

2010-05-01

The effects of dithiolethione modified valproate, diclofenac and sulindac on non-small cell lung cancer (NSCLC) cells were investigated. Sulfur(S)-valproate and S-diclofenac at 1 microg/ml concentrations significantly reduced prostaglandin (PG)E(2) levels in NSCLC cell lines A549 and NCI-H1299 as did the COX-2 inhibitor DuP-697. In vitro, S-valproate, S-diclofenac and S-sulindac half-maximally inhibited the clonal growth of NCI-H1299 cells at 6, 6 and 15 microg/ml, respectively. Using the MTT assay, 10 microg/ml S-valproate, NO-aspirin and Cay10404, a selective COX-2 inhibitor, but not SC-560, a selective COX-1 inhibitor, inhibited the growth of A549 cells. In vivo, 18mg/kg i.p. of S-valproate and S-diclofenac, but not S-sulindac, significantly inhibited A549 or NCI-H1299 xenograft proliferation in nude mice, but had no effect on the nude mouse body weight. The mechanism by which S-valproate and S-diclofenac inhibited the growth of NSCLC cells was investigated. Nitric oxide-aspirin but not S-valproate caused apoptosis of NSCLC cells. By Western blot, S-valproate and S-diclofenac increased E-cadherin but reduced vimentin and ZEB1 (a transcriptional suppressor of E-cadherin) protein expression in NSCLC cells. Because S-valproate and S-diclofenac inhibit the growth of NSCLC cells and reduce PGE(2) levels, they may prove beneficial in the chemoprevention and/or therapy of NSCLC. Published by Elsevier Ireland Ltd.

Nicotine transport in lung and non-lung epithelial cells.

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Takano, Mikihisa; Kamei, Hidetaka; Nagahiro, Machi; Kawami, Masashi; Yumoto, Ryoko

2017-11-01

Nicotine is rapidly absorbed from the lung alveoli into systemic circulation during cigarette smoking. However, mechanism underlying nicotine transport in alveolar epithelial cells is not well understood to date. In the present study, we characterized nicotine uptake in lung epithelial cell lines A549 and NCI-H441 and in non-lung epithelial cell lines HepG2 and MCF-7. Characteristics of [ 3 H]nicotine uptake was studied using these cell lines. Nicotine uptake in A549 cells occurred in a time- and temperature-dependent manner and showed saturation kinetics, with a Km value of 0.31mM. Treatment with some organic cations such as diphenhydramine and pyrilamine inhibited nicotine uptake, whereas treatment with organic cations such as carnitine and tetraethylammonium did not affect nicotine uptake. Extracellular pH markedly affected nicotine uptake, with high nicotine uptake being observed at high pH up to 11.0. Modulation of intracellular pH with ammonium chloride also affected nicotine uptake. Treatment with valinomycin, a potassium ionophore, did not significantly affect nicotine uptake, indicating that nicotine uptake is an electroneutral process. For comparison, we assessed the characteristics of nicotine uptake in another lung epithelial cell line NCI-H441 and in non-lung epithelial cell lines HepG2 and MCF-7. Interestingly, these cell lines showed similar characteristics of nicotine uptake with respect to pH dependency and inhibition by various organic cations. The present findings suggest that a similar or the same pH-dependent transport system is involved in nicotine uptake in these cell lines. A novel molecular mechanism of nicotine transport is proposed. Copyright © 2017 Elsevier Inc. All rights reserved.

Cancer Cell Growth Inhibitory Effect of Bee Venom via Increase of Death Receptor 3 Expression and Inactivation of NF-kappa B in NSCLC Cells

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Kyung Eun Choi

2014-07-01

Full Text Available Our previous findings have demonstrated that bee venom (BV has anti-cancer activity in several cancer cells. However, the effects of BV on lung cancer cell growth have not been reported. Cell viability was determined with trypan blue uptake, soft agar formation as well as DAPI and TUNEL assay. Cell death related protein expression was determined with Western blotting. An EMSA was used for nuclear factor kappaB (NF-κB activity assay. BV (1–5 μg/mL inhibited growth of lung cancer cells by induction of apoptosis in a dose dependent manner in lung cancer cell lines A549 and NCI-H460. Consistent with apoptotic cell death, expression of DR3 and DR6 was significantly increased. However, deletion of DRs by small interfering RNA significantly reversed BV induced cell growth inhibitory effects. Expression of pro-apoptotic proteins (caspase-3 and Bax was concomitantly increased, but the NF-κB activity and expression of Bcl-2 were inhibited. A combination treatment of tumor necrosis factor (TNF-like weak inducer of apoptosis, TNF-related apoptosis-inducing ligand, docetaxel and cisplatin, with BV synergistically inhibited both A549 and NCI-H460 lung cancer cell growth with further down regulation of NF-κB activity. These results show that BV induces apoptotic cell death in lung cancer cells through the enhancement of DR3 expression and inhibition of NF-κB pathway.

NFIX as a Master Regulator for Lung Cancer Progression

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Nor I. A. Rahman

2017-08-01

Full Text Available About 40% of lung cancer cases globally are diagnosed at the advanced stage. Lung cancer has a high mortality and overall survival in stage I disease is only 70%. This study was aimed at finding a candidate of transcription regulator that initiates the mechanism for metastasis by integrating computational and functional studies. The genes involved in lung cancer were retrieved using in silico software. 10 kb promoter sequences upstream were scanned for the master regulator. Transient transfection of shRNA NFIXs were conducted against A549 and NCI-H1299 cell lines. qRT-PCR and functional assays for cell proliferation, migration and invasion were carried out to validate the involvement of NFIX in metastasis. Genome-wide gene expression microarray using a HumanHT-12v4.0 Expression BeadChip Kit was performed to identify differentially expressed genes and construct a new regulatory network. The in silico analysis identified NFIX as a master regulator and is strongly associated with 17 genes involved in the migration and invasion pathways including IL6ST, TIMP1 and ITGB1. Silencing of NFIX showed reduced expression of IL6ST, TIMP1 and ITGB1 as well as the cellular proliferation, migration and invasion processes. The data was integrated with the in silico analyses to find the differentially expressed genes. Microarray analysis showed that 18 genes were expressed differentially in both cell lines after statistical analyses integration between t-test, LIMMA and ANOVA with Benjamini-Hochberg adjustment at p-value < 0.05. A transcriptional regulatory network was created using all 18 genes, the existing regulated genes including the new genes PTCH1, NFAT5 and GGCX that were found highly associated with NFIX, the master regulator of metastasis. This study suggests that NFIX is a promising target for therapeutic intervention that is expected to inhibit metastatic recurrence and improve survival rate.

NCI Statement on the U.S. Surgeon General's "Call to Action to Prevent Skin Cancer"

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As the Federal Government's principal agency for cancer research and training, the National Cancer Institute (NCI) endorses the U.S. Surgeon General’s “Call to Action to Prevent Skin Cancer,” which provides a comprehensive evaluation of the current state of skin cancer prevention efforts in the United States and recommends actions for improvement in the future.

6 Common Cancers - Lung Cancer

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... Bar Home Current Issue Past Issues 6 Common Cancers - Lung Cancer Past Issues / Spring 2007 Table of Contents ... Desperate Housewives. (Photo ©2005 Kathy Hutchins / Hutchins) Lung Cancer Lung cancer causes more deaths than the next three ...

78 FR 2678 - Proposed Collection; Comment Request (60-Day FRN): The National Cancer Institute (NCI...

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2013-01-14

... Request (60-Day FRN): The National Cancer Institute (NCI) SmokefreeTXT (Text Message) Program Evaluation..., Behavioral Scientist/ Health Science Administrator, Division of Cancer Control and Population Sciences, 6130... text message smoking cessation intervention designed for young adult smokers ages 18-29. The Smokefree...

MAPK inhibitors, particularly the JNK inhibitor, increase cell death effects in H2O2-treated lung cancer cells via increased superoxide anion and glutathione depletion.

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Park, Woo Hyun

2018-02-01

Reactive oxygen species (ROS), especially hydrogen peroxide (H2O2), induce apoptosis in cancer cells by regulating mitogen-activated protein kinase (MAPK) signaling pathways. The present study investigated the effects of MAPK inhibitors on cell growth and death as well as changes in ROS and glutathione (GSH) levels in H2O2-treated Calu-6 and A549 lung cancer cells. H2O2 inhibited growth and induced death of Calu-6 and A549 lung cancer cells. All MAPK inhibitors appeared to enhance growth inhibition in H2O2-treated Calu-6 and A549 lung cancer cells and increased the percentage of Annexin V-FITC-positive cells in these cancer cells. Among the MAPK inhibitors, a JNK inhibitor significantly augmented the loss of mitochondrial membrane potential (MMP; ΔΨm) in H2O2-treated Calu-6 and A549 lung cancer cells. Intracellular ROS levels were significantly increased in the H2O2-treated cells at 1 and 24 h. Only the JNK inhibitor increased ROS levels in the H2O2-treated cells at 1 h and all MAPK inhibitors raised superoxide anion levels in these cells at 24 h. In addition, H2O2 induced GSH depletion in Calu-6 and A549 cells and the JNK inhibitor significantly enhanced GSH depletion in H2O2‑treated cells. Each of the MAPK inhibitors altered ROS and GSH levels differently in the Calu-6 and A549 control cells. In conclusion, H2O2 induced growth inhibition and death in lung cancer cells through oxidative stress and depletion of GSH. The enhanced effect of MAPK inhibitors, especially the JNK inhibitor, on cell death in H2O2-treated lung cancer cells was correlated with increased O2•- levels and GSH depletion.

NCI collaborates with Multiple Myeloma Research Foundation

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The National Cancer Institute (NCI) announced a collaboration with the Multiple Myeloma Research Foundation (MMRF) to incorporate MMRF's wealth of genomic and clinical data on the disease into the NCI Genomic Data Commons (GDC), a publicly available datab

Lung Cancer: Glossary

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... professional support team today. Learn More . Find more lung cancer resources. Learn More Donate Today! What is Lung ... to Give How Your Support Helps Events Lung Cancer Awareness © Lung Cancer Alliance. The information presented in this website ...

What Is Lung Cancer?

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... Shareable Graphics Infographics “African-American Men and Lung Cancer” “Lung Cancer Is the Biggest Cancer Killer in Both ... starts in the lungs, it is called lung cancer. Lung cancer begins in the lungs and may spread ...

Molecular biology of the lung cancer

International Nuclear Information System (INIS)

Panov, S.Z.

2005-01-01

Background. Lung cancer is one of the most common malignant diseases and leading cause of cancer death worldwide. The advances in molecular biology and genetics, including the modern microarray technology and rapid sequencing techniques, have enabled a remarkable progress into elucidating the lung cancer ethiopathogenesis. Numerous studies suggest that more than 20 different genetic and epigenetic alterations are accumulating during the pathogenesis of clinically evident pulmonary cancers as a clonal, multistep process. Thus far, the most investigated alterations are the inactivational mutations and losses of tumour suppressor genes and the overexpression of growth-promoting oncogenes. More recently, the acquired epigenetic inactivation of tumour suppressor genes by promoter hypermethylation has been recognized. The early clonal genetic abnormalities that occur in preneoplastic bronchial epithelium damaged by smoking or other carcinogenes are being identified. The molecular distinctions between small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), as well as between tumors with different clinical outcomes have been described. These investigations lead to the h allmarks of lung cancer . Conclusions. It is realistic to expect that the molecular and cell culture-based investigations will lead to discoveries of new clinical applications with the potential to provide new avenues for early diagnosis, risk assessment, prevention, and most important, new more effective treatment approaches for the lung cancer patients. (author)

Lung Cancer

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Lung cancer is one of the most common cancers in the world. It is a leading cause of cancer death in men and women in the United States. Cigarette smoking causes most lung cancers. The more cigarettes you smoke per day and ...

Chlorella vulgaris Induces Apoptosis of Human Non-Small Cell Lung Carcinoma (NSCLC) Cells.

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Zhang, Zhi-Dong; Liang, Kai; Li, Kun; Wang, Guo-Quan; Zhang, Ke-Wei; Cai, Lei; Zhai, Shui-Ting; Chou, Kuo-Chen

2017-01-01

Chlorella vulgaris (C. vulgaris), a unicellular green microalga, has been widely used as a food supplement and reported to have antioxidant and anticancer properties. The current study was designed to assess the cytotoxic, apoptotic, and DNA-damaging effects of C. vulgaris growth factor (CGF), hot water C. vulgaris extracts, inlung tumor A549 and NCI-H460 cell lines. A549 cells, NCI-H460 cells, and normal human fibroblasts were treated with CGF at various concentrations (0-300 μg/ml) for 24 hr. The comet assay and γH2AX assay showed DNA damage in A549 and NCI-H460 cells upon CGF exposure. Evaluation of apoptosis by the TUNEL assay and DNA fragmentation analysis by agarose gel electrophoresis showed that CGF induced apoptosis in A549 and NCI-H460 cells. Chlorella vulgaris hot water extract induced apoptosis and DNA damage in human lung carcinoma cells. CGF can thus be considered a potential cytotoxic or genotoxic drug for treatment of lung carcinoma. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The CD44(high tumorigenic subsets in lung cancer biospecimens are enriched for low miR-34a expression.

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Saroj K Basak

Full Text Available Cellular heterogeneity is an integral part of cancer development and progression. Progression can be associated with emergence of cells that exhibit high phenotypic plasticity (including "de-differentiation" to primitive developmental states, and aggressive behavioral properties (including high tumorigenic potentials. We observed that many biomarkers that are used to identify Cancer Stem Cells (CSC can label cell subsets in an advanced clinical stage of lung cancer (malignant pleural effusions, or MPE. Thus, CSC-biomarkers may be useful for live sorting functionally distinct cell subsets from individual tumors, which may enable investigators to hone in on the molecular basis for functional heterogeneity. We demonstrate that the CD44(hi (CD44-high cancer cell subsets display higher clonal, colony forming potential than CD44(lo cells (n=3 and are also tumorigenic (n=2/2 when transplanted in mouse xenograft model. The CD44(hi subsets express different levels of embryonal (de-differentiation markers or chromatin regulators. In archived lung cancer tissues, ALDH markers co-localize more with CD44 in squamous cell carcinoma (n=5/7 than Adeno Carcinoma (n=1/12. MPE cancer cells and a lung cancer cell line (NCI-H-2122 exhibit chromosomal abnormalities and 1p36 deletion (n=3/3. Since miR-34a maps to the 1p36 deletion site, low miR-34a expression levels were detected in these cells. The colony forming efficiency of CD44(hi cells, characteristic property of CSC, can be inhibited by mir-34a replacement in these samples. In addition the highly tumorigenic CD44(hi cells are enriched for cells in the G2 phase of cell cycle.

RANK rewires energy homeostasis in lung cancer cells and drives primary lung cancer.

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Rao, Shuan; Sigl, Verena; Wimmer, Reiner Alois; Novatchkova, Maria; Jais, Alexander; Wagner, Gabriel; Handschuh, Stephan; Uribesalgo, Iris; Hagelkruys, Astrid; Kozieradzki, Ivona; Tortola, Luigi; Nitsch, Roberto; Cronin, Shane J; Orthofer, Michael; Branstetter, Daniel; Canon, Jude; Rossi, John; D'Arcangelo, Manolo; Botling, Johan; Micke, Patrick; Fleur, Linnea La; Edlund, Karolina; Bergqvist, Michael; Ekman, Simon; Lendl, Thomas; Popper, Helmut; Takayanagi, Hiroshi; Kenner, Lukas; Hirsch, Fred R; Dougall, William; Penninger, Josef M

2017-10-15

Lung cancer is the leading cause of cancer deaths. Besides smoking, epidemiological studies have linked female sex hormones to lung cancer in women; however, the underlying mechanisms remain unclear. Here we report that the receptor activator of nuclear factor-kB (RANK), the key regulator of osteoclastogenesis, is frequently expressed in primary lung tumors, an active RANK pathway correlates with decreased survival, and pharmacologic RANK inhibition reduces tumor growth in patient-derived lung cancer xenografts. Clonal genetic inactivation of KRas G12D in mouse lung epithelial cells markedly impairs the progression of KRas G12D -driven lung cancer, resulting in a significant survival advantage. Mechanistically, RANK rewires energy homeostasis in human and murine lung cancer cells and promotes expansion of lung cancer stem-like cells, which is blocked by inhibiting mitochondrial respiration. Our data also indicate survival differences in KRas G12D -driven lung cancer between male and female mice, and we show that female sex hormones can promote lung cancer progression via the RANK pathway. These data uncover a direct role for RANK in lung cancer and may explain why female sex hormones accelerate lung cancer development. Inhibition of RANK using the approved drug denosumab may be a therapeutic drug candidate for primary lung cancer. © 2017 Rao et al.; Published by Cold Spring Harbor Laboratory Press.

Epidemiology of Lung Cancer

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Brock, Malcolm V.; Ford, Jean G.; Samet, Jonathan M.; Spivack, Simon D.

2013-01-01

Background: Ever since a lung cancer epidemic emerged in the mid-1900s, the epidemiology of lung cancer has been intensively investigated to characterize its causes and patterns of occurrence. This report summarizes the key findings of this research. Methods: A detailed literature search provided the basis for a narrative review, identifying and summarizing key reports on population patterns and factors that affect lung cancer risk. Results: Established environmental risk factors for lung cancer include smoking cigarettes and other tobacco products and exposure to secondhand tobacco smoke, occupational lung carcinogens, radiation, and indoor and outdoor air pollution. Cigarette smoking is the predominant cause of lung cancer and the leading worldwide cause of cancer death. Smoking prevalence in developing nations has increased, starting new lung cancer epidemics in these nations. A positive family history and acquired lung disease are examples of host factors that are clinically useful risk indicators. Risk prediction models based on lung cancer risk factors have been developed, but further refinement is needed to provide clinically useful risk stratification. Promising biomarkers of lung cancer risk and early detection have been identified, but none are ready for broad clinical application. Conclusions: Almost all lung cancer deaths are caused by cigarette smoking, underscoring the need for ongoing efforts at tobacco control throughout the world. Further research is needed into the reasons underlying lung cancer disparities, the causes of lung cancer in never smokers, the potential role of HIV in lung carcinogenesis, and the development of biomarkers. PMID:23649439

Readability of Online Patient Educational Resources Found on NCI-Designated Cancer Center Web Sites.

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Rosenberg, Stephen A; Francis, David; Hullett, Craig R; Morris, Zachary S; Fisher, Michael M; Brower, Jeffrey V; Bradley, Kristin A; Anderson, Bethany M; Bassetti, Michael F; Kimple, Randall J

2016-06-01

The NIH and Department of Health & Human Services recommend online patient information (OPI) be written at a sixth grade level. We used a panel of readability analyses to assess OPI from NCI-Designated Cancer Center (NCIDCC) Web sites. Cancer.gov was used to identify 68 NCIDCC Web sites from which we collected both general OPI and OPI specific to breast, prostate, lung, and colon cancers. This text was analyzed by 10 commonly used readability tests: the New Dale-Chall Readability Formula, Flesch Reading Ease scale, Flesch-Kinaid Grade Level, FORCAST scale, Fry Readability Graph, Simple Measure of Gobbledygook test, Gunning Frequency of Gobbledygook index, New Fog Count, Raygor Readability Estimate Graph, and Coleman-Liau Index. We tested the hypothesis that the readability of NCIDCC OPI was written at the sixth grade level. Secondary analyses were performed to compare readability of OPI between comprehensive and noncomprehensive centers, by region, and to OPI produced by the American Cancer Society (ACS). A mean of 30,507 words from 40 comprehensive and 18 noncomprehensive NCIDCCs was analyzed (7 nonclinical and 3 without appropriate OPI were excluded). Using a composite grade level score, the mean readability score of 12.46 (ie, college level: 95% CI, 12.13-12.79) was significantly greater than the target grade level of 6 (middle-school: Preadability metrics (P<.05). ACS OPI provides easier language, at the seventh to ninth grade level, across all tests (P<.01). OPI from NCIDCC Web sites is more complex than recommended for the average patient. Copyright © 2016 by the National Comprehensive Cancer Network.

Lung cancer - small cell

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Cancer - lung - small cell; Small cell lung cancer; SCLC ... About 15% of all lung cancer cases are SCLC. Small cell lung cancer is slightly more common in men than women. Almost all cases of SCLC are ...

Ratio Based Biomarkers for the Prediction of Cancer Survival | NCI Technology Transfer Center | TTC

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The NCI seeks licensees or co-development partners for this technology, which describes compositions, methods and kits for identifying, characterizing biomolecules expressed in a sample that are associated with the presence, the development, or progression of cancer.

18FDG-PET predicts pharmacodynamic response to OSI-906, a dual IGF-1R/IR inhibitor, in preclinical mouse models of lung cancer.

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McKinley, Eliot T; Bugaj, Joseph E; Zhao, Ping; Guleryuz, Saffet; Mantis, Christine; Gokhale, Prafulla C; Wild, Robert; Manning, H Charles

2011-05-15

To evaluate 2-deoxy-2-[(18)F]fluoro-d-glucose positron emission tomography imaging ((18)FDG-PET) as a predictive, noninvasive, pharmacodynamic (PD) biomarker of response following administration of a small-molecule insulin-like growth factor-1 receptor and insulin receptor (IGF-1R/IR) inhibitor, OSI-906. In vitro uptake studies of (3)H-2-deoxy glucose following OSI-906 exposure were conducted evaluating correlation of dose with inhibition of IGF-1R/IR as well as markers of downstream pathways and glucose metabolism. Similarly, in vivo PD effects were evaluated in human tumor cell line xenografts propagated in athymic nude mice by (18)FDG-PET at 2, 4, and 24 hours following a single treatment of OSI-906 for the correlation of inhibition of receptor targets and downstream markers. Uptake of (3)H-2-deoxy glucose and (18)FDG was significantly diminished following OSI-906 exposure in sensitive tumor cells and subcutaneous xenografts (NCI-H292) but not in an insensitive model lacking IGF-1R expression (NCI-H441). Diminished PD (18)FDG-PET, collected immediately following the initial treatment agreed with inhibition of pIGF-1R/pIR, reduced PI3K (phosphoinositide 3-kinase) and MAPK (mitogen activated protein kinase) pathway activity, and predicted tumor growth arrest as measured by high-resolution ultrasound imaging. (18)FDG-PET seems to serve as a rapid, noninvasive PD marker of IGF-1R/IR inhibition following a single dose of OSI-906 and should be explored clinically as a predictive clinical biomarker in patients undergoing IGF-1R/IR-directed cancer therapy. ©2011 AACR.

Intersections of lung progenitor cells, lung disease and lung cancer.

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Kim, Carla F

2017-06-30

The use of stem cell biology approaches to study adult lung progenitor cells and lung cancer has brought a variety of new techniques to the field of lung biology and has elucidated new pathways that may be therapeutic targets in lung cancer. Recent results have begun to identify the ways in which different cell populations interact to regulate progenitor activity, and this has implications for the interventions that are possible in cancer and in a variety of lung diseases. Today's better understanding of the mechanisms that regulate lung progenitor cell self-renewal and differentiation, including understanding how multiple epigenetic factors affect lung injury repair, holds the promise for future better treatments for lung cancer and for optimising the response to therapy in lung cancer. Working between platforms in sophisticated organoid culture techniques, genetically engineered mouse models of injury and cancer, and human cell lines and specimens, lung progenitor cell studies can begin with basic biology, progress to translational research and finally lead to the beginnings of clinical trials. Copyright ©ERS 2017.

Intersections of lung progenitor cells, lung disease and lung cancer

Directory of Open Access Journals (Sweden)

Carla F. Kim

2017-06-01

Full Text Available The use of stem cell biology approaches to study adult lung progenitor cells and lung cancer has brought a variety of new techniques to the field of lung biology and has elucidated new pathways that may be therapeutic targets in lung cancer. Recent results have begun to identify the ways in which different cell populations interact to regulate progenitor activity, and this has implications for the interventions that are possible in cancer and in a variety of lung diseases. Today's better understanding of the mechanisms that regulate lung progenitor cell self-renewal and differentiation, including understanding how multiple epigenetic factors affect lung injury repair, holds the promise for future better treatments for lung cancer and for optimising the response to therapy in lung cancer. Working between platforms in sophisticated organoid culture techniques, genetically engineered mouse models of injury and cancer, and human cell lines and specimens, lung progenitor cell studies can begin with basic biology, progress to translational research and finally lead to the beginnings of clinical trials.

Gigantol Inhibits Epithelial to Mesenchymal Process in Human Lung Cancer Cells

Directory of Open Access Journals (Sweden)

Thitita Unahabhokha

2016-01-01

Full Text Available Lung cancer remains a leading public health problem as evidenced by its increasing death rate. The main cause of death in lung cancer patients is cancer metastasis. The metastatic behavior of lung cancer cells becomes enhanced when cancer cells undergo epithelial to mesenchymal transition (EMT. Gigantol, a bibenzyl compound extracted from the Thai orchid, Dendrobium draconis, has been shown to have promising therapeutic potential against cancer cells, which leads to the hypothesis that gigantol may be able to inhibit the fundamental EMT process in cancer cells. This study has demonstrated for the first time that gigantol possesses the ability to suppress EMT in non-small cell lung cancer H460 cells. Western blot analysis has revealed that gigantol attenuates the activity of ATP-dependent tyrosine kinase (AKT, thereby inhibiting the expression of the major EMT transcription factor, Slug, by both decreasing its transcription and increasing its degradation. The inhibitory effects of gigantol on EMT result in a decrease in the level of migration in H460 lung cancer cells. The results of this study emphasize the potential of gigantol for further development against lung cancer metastasis.

Colon cancer proliferating desulfosinigrin in wasabi (Wasabia japonica).

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Weil, Marvin J; Zhang, Yanjun; Nair, Muraleedharan G

2004-01-01

A reduced incidence of different types of cancer has been linked to consumption of Brassica vegetables, and there is evidence that glucosinolates (GSLs) and their hydrolysis products play a role in reducing cancer risk. Wasabi (Wasabia japonica) and horseradish (Armoracia rusticana), both Brassica vegetables, are widely used condiments both in Japanese cuisine and in the United States. Desulfosinigrin (DSS) (1) was isolated from a commercially available wasabi powder and from fresh wasabi roots. Sinigrin (2) was isolated from horseradish roots. DSS and sinigrin were evaluated for their inhibitory effects on cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes, on lipid peroxidation, and on the proliferation of human colon (HCT-116), breast (MCF-7), lung (NCIH460), and central nervous system (CNS, SF-268) cancer cell lines. DSS did not inhibit COX enzymes or lipid peroxidation at 250 microg/ml. Sinigrin inhibited lipid peroxidation by 71% at 250 microg/ml. However, DSS promoted the growth of HCT-116 (colon) and NCI H460 (lung) human cancer cells as determined by the MTT assay in a concentration-dependent manner. At 3.72 microg/ml, a 27% increase in the number of viable human HCT-116 colon cancer cells was observed; the corresponding increases at 7.50 and 15 microg/ml were 42 and 69%, respectively. At 60 microg/ml, DSS doubled the number of HCT-16 colon cancer cells. For NCI H460 human lung cancer cells, DSS at 60 microg/ml increased the cell number by 20%. Sinigrin showed no proliferating effect on the tumor cells tested. This is the first report of the tumor cell-proliferating activity by a desulfoglucosinolate, the biosynthetic precursor of GSLs found in Brassica spp.

Staging of Lung Cancer

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... LUNG CANCER MINI-SERIES #2 Staging of Lung Cancer Once your lung cancer is diagnosed, staging tells you and your health care provider about ... at it under a microscope. The stages of lung cancer are listed as I, II, III, and IV ...

CellMiner: a relational database and query tool for the NCI-60 cancer cell lines

Directory of Open Access Journals (Sweden)

Reinhold William C

2009-06-01

Full Text Available Abstract Background Advances in the high-throughput omic technologies have made it possible to profile cells in a large number of ways at the DNA, RNA, protein, chromosomal, functional, and pharmacological levels. A persistent problem is that some classes of molecular data are labeled with gene identifiers, others with transcript or protein identifiers, and still others with chromosomal locations. What has lagged behind is the ability to integrate the resulting data to uncover complex relationships and patterns. Those issues are reflected in full form by molecular profile data on the panel of 60 diverse human cancer cell lines (the NCI-60 used since 1990 by the U.S. National Cancer Institute to screen compounds for anticancer activity. To our knowledge, CellMiner is the first online database resource for integration of the diverse molecular types of NCI-60 and related meta data. Description CellMiner enables scientists to perform advanced querying of molecular information on NCI-60 (and additional types through a single web interface. CellMiner is a freely available tool that organizes and stores raw and normalized data that represent multiple types of molecular characterizations at the DNA, RNA, protein, and pharmacological levels. Annotations for each project, along with associated metadata on the samples and datasets, are stored in a MySQL database and linked to the molecular profile data. Data can be queried and downloaded along with comprehensive information on experimental and analytic methods for each data set. A Data Intersection tool allows selection of a list of genes (proteins in common between two or more data sets and outputs the data for those genes (proteins in the respective sets. In addition to its role as an integrative resource for the NCI-60, the CellMiner package also serves as a shell for incorporation of molecular profile data on other cell or tissue sample types. Conclusion CellMiner is a relational database tool for

Metabolic cooperation between co-cultured lung cancer cells and lung fibroblasts.

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Koukourakis, Michael I; Kalamida, Dimitra; Mitrakas, Achilleas G; Liousia, Maria; Pouliliou, Stamatia; Sivridis, Efthimios; Giatromanolaki, Alexandra

2017-11-01

Cooperation of cancer cells with stromal cells, such as cancer-associated fibroblasts (CAFs), has been revealed as a mechanism sustaining cancer cell survival and growth. In the current study, we focus on the metabolic interactions of MRC5 lung fibroblasts with lung cancer cells (A549 and H1299) using co-culture experiments and studying changes of the metabolic protein expression profile and of their growth and migration abilities. Using western blotting, confocal microscopy and RT-PCR, we observed that in co-cultures MRC5 respond by upregulating pyruvate dehydrogenase (PDH) and the monocarboxylate transporter MCT1. In contrast, cancer cells increase the expression of glucose transporters (GLUT1), LDH5, PDH kinase and the levels of phosphorylated/inactivated pPDH. H1299 cells growing in the same culture medium with fibroblasts exhibit a 'metastasis-like' phenomenon by forming nests within the fibroblast area. LDH5 and pPDH were drastically upregulated in these nests. The growth rate of both MRC5 and cancer cells increased in co-cultures. Suppression of LDHA or PDK1 in cancer cells abrogates the stimulatory signal from cancer cells to fibroblasts. Incubation of MRC5 fibroblasts with lactate resulted in an increase of LDHB and of PDH expression. Silencing of PDH gene in fibroblasts, or silencing of PDK1 or LDHA gene in tumor cells, impedes cancer cell's migration ability. Overall, a metabolic cooperation between lung cancer cells and fibroblasts has been confirmed in the context of direct Warburg effect, thus the fibroblasts reinforce aerobic metabolism to support the intensified anaerobic glycolytic pathways exploited by cancer cells.

Synergistic Effect of Subtoxic-dose Cisplatin and TRAIL to Mediate Apoptosis by Down-regulating Decoy Receptor 2 and Up-regulating Caspase-8, Caspase-9 and Bax Expression on NCI-H460 and A549 Cells

Directory of Open Access Journals (Sweden)

Xiaoyan Zhang

2013-05-01

Full Text Available Objective(s: Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL can selectively induce apoptosis in tumor cells, more than half of tumors including non-small cell lung cancer (NSCLC exhibit TRAIL-resistance. The purpose of this study was to determine whether subtoxic-dose cisplatin and TRAIL could synergistically enhance apoptosis on NSCLC cells and investigate its underlying mechanisms. Materials and Methods:NCI-H460 and A549 cells were treated with TRAIL alone, cisplatin alone or combination treatment in this study. The cytotoxicity was evaluated according to Sulforhodamine B assay, and apoptosis was examined using Hoechst 33342 staining and flow cytometry. The mRNA and protein levels of TRAIL receptors and apoptotic proteins including caspase-8, caspase-9, Bcl-2 and Bax were determined by RT-PCR and Western blotting, respectively. Results:Our results showed that NCI-H460 cells were sensitive to TRAIL, whereas A549 cells were resistant. However, subtoxic-dose cisplatin could enhance the both cells to TRAIL-mediated cell proliferation inhibition and apoptosis. The underlying mechanisms might be associated with the down-regulation of DcR2 and up-regulation of Caspase-8, Caspase-9 and Bax. Conclusion:Subtoxic-dose cisplatin could enhance both TRAIL- sensitive and TRAIL- resistant NSCLC cells to TRAIL-mediated apoptosis. These findings motivated further studies to evaluate such a combinatory therapeutic strategy against NSCLC in the animal models.

Genetics Home Reference: lung cancer

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... Share: Email Facebook Twitter Home Health Conditions Lung cancer Lung cancer Printable PDF Open All Close All Enable Javascript ... cancer, childhood Additional NIH Resources (3 links) National Cancer Institute: Lung Cancer Overview National Cancer Institute: Lung Cancer Prevention ...

Diet and lung cancer

DEFF Research Database (Denmark)

Fabricius, P; Lange, Peter

2003-01-01

Lung cancer is the leading cause of cancer-related deaths worldwide. While cigarette smoking is of key importance, factors such as diet also play a role in the development of lung cancer. MedLine and Embase were searched with diet and lung cancer as the key words. Recently published reviews and l...... are only ameliorated to a minor degree by a healthy diet.......Lung cancer is the leading cause of cancer-related deaths worldwide. While cigarette smoking is of key importance, factors such as diet also play a role in the development of lung cancer. MedLine and Embase were searched with diet and lung cancer as the key words. Recently published reviews...... and large well designed original articles were preferred to form the basis for the present article. A diet rich in fruit and vegetables reduces the incidence of lung cancer by approximately 25%. The reduction is of the same magnitude in current smokers, ex-smokers and never smokers. Supplementation...

Epidemiology of Lung Cancer.

Science.gov (United States)

Schwartz, Ann G; Cote, Michele L

2016-01-01

Lung cancer continues to be one of the most common causes of cancer death despite understanding the major cause of the disease: cigarette smoking. Smoking increases lung cancer risk 5- to 10-fold with a clear dose-response relationship. Exposure to environmental tobacco smoke among nonsmokers increases lung cancer risk about 20%. Risks for marijuana and hookah use, and the new e-cigarettes, are yet to be consistently defined and will be important areas for continued research as use of these products increases. Other known environmental risk factors include exposures to radon, asbestos, diesel, and ionizing radiation. Host factors have also been associated with lung cancer risk, including family history of lung cancer, history of chronic obstructive pulmonary disease and infections. Studies to identify genes associated with lung cancer susceptibility have consistently identified chromosomal regions on 15q25, 6p21 and 5p15 associated with lung cancer risk. Risk prediction models for lung cancer typically include age, sex, cigarette smoking intensity and/or duration, medical history, and occupational exposures, however there is not yet a risk prediction model currently recommended for general use. As lung cancer screening becomes more widespread, a validated model will be needed to better define risk groups to inform screening guidelines.

Polymorphisms of Selected DNA Repair Genes and Lung Cancer in Chromium Exposure.

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Halasova, E; Matakova, T; Skerenova, M; Krutakova, M; Slovakova, P; Dzian, A; Javorkova, S; Pec, M; Kypusova, K; Hamzik, J

2016-01-01

Chromium is a well-known mutagen and carcinogen involved in lung cancer development. DNA repair genes play an important role in the elimination of genetic changes caused by chromium exposure. In the present study, we investigated the polymorphisms of the following DNA repair genes: XRCC3, participating in the homologous recombination repair, and hMLH1 and hMSH2, functioning in the mismatch repair. We focused on the risk the polymorphisms present in the development of lung cancer regarding the exposure to chromium. We analyzed 106 individuals; 45 patients exposed to chromium with diagnosed lung cancer and 61 healthy controls. Genotypes were determined by a PCR-RFLP method. We unravelled a potential for increased risk of lung cancer development in the hMLH1 (rs1800734) AA genotype in the recessive model. In conclusion, gene polymorphisms in the DNA repair genes underscores the risk of lung cancer development in chromium exposed individuals.

NCI Requests Targets for Monoclonal Antibody Production and Characterization | Office of Cancer Clinical Proteomics Research

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In an effort to provide well-characterized monoclonal antibodies to the scientific community, NCI's Antibody Characterization Program requests cancer-related protein targets for affinity production and distribution. Submissions will be accepted through July 9, 2012.

Radiation Therapy for Lung Cancer

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... is almost always due to smoking. TREATING LUNG CANCER Lung cancer treatment depends on several factors, including the ... org TARGETING CANCER CARE Radiation Therapy for Lung Cancer Lung cancer is the second most common cancer in ...

An NCI perspective on creating sustainable biospecimen resources.

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Vaught, Jimmie; Rogers, Joyce; Myers, Kimberly; Lim, Mark David; Lockhart, Nicole; Moore, Helen; Sawyer, Sherilyn; Furman, Jeffrey L; Compton, Carolyn

2011-01-01

High-quality biospecimens with appropriate clinical annotation are critical in the era of personalized medicine. It is now widely recognized that biospecimen resources need to be developed and operated under established scientific, technical, business, and ethical/legal standards. To date, such standards have not been widely practiced, resulting in variable biospecimen quality that may compromise research efforts. The National Cancer Institute (NCI) Office of Biorepositories and Biospecimen Research (OBBR) was established in 2005 to coordinate NCI's biospecimen resource activities and address those issues that affect access to the high-quality specimens and data necessary for its research enterprises as well as the broader translational research field. OBBR and the NCI Biorepository Coordinating Committee developed NCI's "Best Practices for Biospecimen Resources" after consultation with a broad array of experts. A Biospecimen Research Network was established to fund research to develop additional evidence-based practices. Although these initiatives will improve the overall availability of high-quality specimens and data for cancer research, OBBR has been authorized to implement a national biobanking effort, cancer HUman Biobank (caHUB). caHUB will address systematically the gaps in knowledge needed to improve the state-of-the-science and strengthen the standards for human biobanking. This commentary outlines the progressive efforts by NCI in technical, governance, and economic considerations that will be important as the new caHUB enterprise is undertaken.

Interplay between the lung microbiome and lung cancer.

Science.gov (United States)

Mao, Qixing; Jiang, Feng; Yin, Rong; Wang, Jie; Xia, Wenjie; Dong, Gaochao; Ma, Weidong; Yang, Yao; Xu, Lin; Hu, Jianzhong

2018-02-28

The human microbiome confers benefits or disease susceptibility to the human body through multiple pathways. Disruption of the symbiotic balance of the human microbiome is commonly found in systematic diseases such as diabetes, obesity, and chronic gastric diseases. Emerging evidence has suggested that dysbiosis of the microbiota may also play vital roles in carcinogenesis at multiple levels, e.g., by affecting metabolic, inflammatory, or immune pathways. Although the impact of the gut microbiome on the digestive cancer has been widely explored, few studies have investigated the interplay between the microbiome and lung cancer. Some recent studies have shown that certain microbes and microbiota dysbiosis are correlated with development of lung cancer. In this mini-review, we briefly summarize current research findings describing the relationship between the lung microbiome and lung cancer. We further discuss the potential mechanisms through which the lung microbiome may play a role in lung carcinogenesis and impact lung cancer treatment. A better knowledge of the interplay between the lung microbiome and lung cancer may promote the development of innovative strategies for early prevention and personalized treatment in lung cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

Best Performers Announced for the NCI-CPTAC DREAM Proteogenomics Computational Challenge | Office of Cancer Clinical Proteomics Research

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The National Cancer Institute (NCI) Clinical Proteomic Tumor Analysis Consortium (CPTAC) is pleased to announce that teams led by Jaewoo Kang (Korea University), and Yuanfang Guan with Hongyang Li (University of Michigan) as the best performers of the NCI-CPTAC DREAM Proteogenomics Computational Challenge. Over 500 participants from 20 countries registered for the Challenge, which offered $25,000 in cash awards contributed by the NVIDIA Foundation through its Compute the Cure initiative.

Incidence of non-lung solid cancers in Czech uranium miners: A case-cohort study

International Nuclear Information System (INIS)

Kulich, M.; Rericha, V.; Rericha, R.; Shore, D.L.; Sandler, D.P.

2011-01-01

Objectives: Uranium miners are chronically exposed to radon and its progeny, which are known to cause lung cancer and may be associated with leukemia. This study was undertaken to evaluate risk of non-lung solid cancers among uranium miners in Pribram region, Czech Republic. Methods: A retrospective stratified case-cohort study in a cohort of 22,816 underground miners who were employed between 1949 and 1975. All incident non-lung solid cancers were ascertained among miners who worked underground for at least 12 months (n=1020). A subcohort of 1707 subjects was randomly drawn from the same population by random sampling stratified on age. The follow-up period lasted from 1977 to 1996. Results: Relative risks comparing 180 WLM (90th percentile) of cumulative lifetime radon exposure to 3 WLM (10th percentile) were 0.88 for all non-lung solid cancers combined (95% CI 0.73-1.04, n=1020), 0.87 for all digestive cancers (95% CI 0.69-1.09, n=561), 2.39 for gallbladder cancer (95% CI 0.52-10.98, n=13), 0.79 for larynx cancer (95% CI 0.38-1.64, n=62), 2.92 for malignant melanoma (95% CI 0.91-9.42, n=23), 0.84 for bladder cancer (95% CI 0.43-1.65, n=73), and 1.13 for kidney cancer (95% CI 0.62-2.04, n=66). No cancer type was significantly associated with radon exposure; only malignant melanoma and gallbladder cancer showed elevated but non-significant association with radon. Conclusions: Radon was not significantly associated with incidence of any cancer of interest, although a positive association of radon with malignant melanoma and gallbladder cancer cannot be entirely ruled out. - Research highlights: → Uranium miners are chronically exposed to radon. → We evaluate risk of non-lung solid cancers among uranium miners. → No cancer type was significantly associated with radon exposure. → Malignant melanoma and gallbladder cancer showed non-significant elevated risk.

Lung cancer in elderly

International Nuclear Information System (INIS)

Wagnerova, M.

2007-01-01

Lung cancer is the leading cause of cancer deaths in Europe and USA. The median age of diagnosis is currently 69 years, however this is gradually increasing with the aging population. Patients over age of 70 represent 40 % of all patients with non-small cell lung cancer. Age alone has not been found to be a significant prognostic factor in many malignancies, including lung cancer with performance status and stage being of greater importance. In lung cancer it is also evident that older patients gain equivalent benefit from cancer therapies as their younger counterparts. Elderly patients are under-treated in all aspects of their disease course from histological diagnosis to active therapy with surgical resection, radiotherapy or chemotherapy, irrespective of performance status or co-morbidities. Elderly patients are also underrepresented in lung cancer clinical trials. In this review is presented knowledge about lung cancer in elderly. (author)

Incidence of non-lung solid cancers in Czech uranium miners: a case-cohort study.

Science.gov (United States)

Kulich, M; Reřicha, V; Reřicha, R; Shore, D L; Sandler, D P

2011-04-01

Uranium miners are chronically exposed to radon and its progeny, which are known to cause lung cancer and may be associated with leukemia. This study was undertaken to evaluate risk of non-lung solid cancers among uranium miners in Příbram region, Czech Republic. A retrospective stratified case-cohort study in a cohort of 22,816 underground miners who were employed between 1949 and 1975. All incident non-lung solid cancers were ascertained among miners who worked underground for at least 12 months (n=1020). A subcohort of 1707 subjects was randomly drawn from the same population by random sampling stratified on age. The follow-up period lasted from 1977 to 1996. Relative risks comparing 180 WLM (90th percentile) of cumulative lifetime radon exposure to 3 WLM (10th percentile) were 0.88 for all non-lung solid cancers combined (95% CI 0.73-1.04, n=1020), 0.87 for all digestive cancers (95% CI 0.69-1.09, n=561), 2.39 for gallbladder cancer (95% CI 0.52-10.98, n=13), 0.79 for larynx cancer (95% CI 0.38-1.64, n=62), 2.92 for malignant melanoma (95% CI 0.91-9.42, n=23), 0.84 for bladder cancer (95% CI 0.43-1.65, n=73), and 1.13 for kidney cancer (95% CI 0.62-2.04, n=66). No cancer type was significantly associated with radon exposure; only malignant melanoma and gallbladder cancer showed elevated but non-significant association with radon. Radon was not significantly associated with incidence of any cancer of interest, although a positive association of radon with malignant melanoma and gallbladder cancer cannot be entirely ruled out. Copyright © 2011 Elsevier Inc. All rights reserved.

miR-375 is highly expressed and possibly transactivated by achaete-scute complex homolog 1 in small-cell lung cancer cells

Institute of Scientific and Technical Information of China (English)

Huijie Zhao; Lei Zhu; Yujuan Jin; Hongbin Ji; Xiumin Yan; Xueliang Zhu

2012-01-01

In this study,we identified five miRNAs highly expressed in the small-cell lung cancer (SCLC) cell line NCI-H209.Among them,the expression levels of miR-375 were dramatically elevated in all SCLC cell lines examined,coincident with the expression of the transcription factor achaete-scute complex homolog 1 (ASCL1).Moreover,miR-375 was upregulated and correlated with ASCL1 in the cell lines generated from mouse SCLC-like tumors as well.Dual-luciferase assays further showed that ASCL1 activated the expression of miR-375 by binding to the three E-box elements in the miR-375 promoter.These results imply a role of ASCL1 in SCLC via the upregulation of miR-375.

Anti-lung cancer effects of novel ginsenoside 25-OCH(3)-PPD.

Science.gov (United States)

Wang, Wei; Rayburn, Elizabeth R; Hang, Jie; Zhao, Yuqing; Wang, Hui; Zhang, Ruiwen

2009-09-01

20(S)-25-methoxyl-dammarane-3beta, 12beta, 20-triol (25-OCH(3)-PPD), a newly identified natural product from Panax notoginseng, exhibits activity against a variety of cancer cells. Herein, we report the effects of this compound on human A549, H358, and H838 lung cancer cells, and compare these effects with a control lung epithelial cell line, BEAS-2B. 25-OCH(3)-PPD decreased survival, inhibited proliferation, and induced apoptosis and G1 cell cycle arrest in the lung cancer cell lines. The P. notoginseng compound also decreased the levels of proteins associated with cell proliferation and cell survival. Moreover, 25-OCH(3)-PPD inhibited the growth of A549 lung cancer xenograft tumors. 25-OCH(3)-PPD demonstrated low toxicity to non-cancer cells, and no observable toxicity was seen when the compound was administered to animals. In conclusion, our preclinical data indicate that 25-OCH(3)-PPD is a potential therapeutic agent in vitro and in vivo, and further preclinical and clinical development of this agent for lung cancer is warranted.

Diet and lung cancer

DEFF Research Database (Denmark)

Fabricius, P; Lange, Peter

2003-01-01

Lung cancer is the leading cause of cancer-related deaths worldwide. While cigarette smoking is of key importance, factors such as diet also play a role in the development of lung cancer. MedLine and Embase were searched with diet and lung cancer as the key words. Recently published reviews...... and large well designed original articles were preferred to form the basis for the present article. A diet rich in fruit and vegetables reduces the incidence of lung cancer by approximately 25%. The reduction is of the same magnitude in current smokers, ex-smokers and never smokers. Supplementation...... with vitamins A, C and E and beta-carotene offers no protection against the development of lung cancer. On the contrary, beta-carotene supplementation has, in two major randomised intervention trials, resulted in an increased mortality. Smoking remains the leading cause of lung cancer. The adverse effects...

In vitro growth inhibition and cytotoxicity of Euphorbia caducifolia against four human cancer cell lines and its phytochemical characterisation.

Science.gov (United States)

Bano, Shaista; Siddiqui, Bina Shaheen; Farooq, Ahsana Dar; Begum, Sabira; Siddiqui, Faheema; Kashif, Muhammad; Azhar, Mudassar

2017-12-01

Several Euphorbia species have been used in folklore as cancer remedies, however, scientific studies on the cytotoxicity (in vitro studies) of Euphorbia caducifolia are lacking. In present study, anticancer potential of E. caducifolia aerial parts ethanol extract and its fractions were evaluated against human lung (NCI-H460), breast (MCF-7), prostate (PC-3) and cervical (HeLa) cancer cell lines, using sulphorhodamine-B in vitro cytotoxicity (in vitro studies) assay. The ethanol extract demonstrated growth inhibitory effect against all aforementioned cancer cell lines with IC 50 , 19-135 μg/mL and LC 50 , ~220 μg/mL, and its petroleum ether fraction obtained on bioactivity guided fraction showed highest activity with IC 50 , 28-70 μg/mL and LC 50 , 71 μg/mL against NCI-H460 and MCF-7 cell lines. Its phytochemicals were analysed by gas chromatography-mass spectrometry (GC-MS). The present study provides scientific justification for its traditional use against cancer.

Lung cancer in women

Directory of Open Access Journals (Sweden)

Barrera-Rodriguez R

2012-12-01

Full Text Available Raúl Barrera-Rodriguez,1 Jorge Morales-Fuentes2 1Biochemistry and Environmental Medicine Laboratory, National Institute of Respiratory Disease, 2Lung Cancer Medical Service, National Institute of Respiratory Disease, Tlalpan, Mexico City, Distrito Federal, Mexico Both authors contributed equally to this workAbstract: Recent biological advances in tumor research provide clear evidence that lung cancer in females is different from that in males. These differences appear to have a direct impact on the clinical presentation, histology, and outcomes of lung cancer. Women are more likely to present with lung adenocarcinoma, tend to receive a diagnosis at an earlier age, and are more likely to be diagnosed with localized disease. Women may also be more predisposed to molecular aberrations resulting from the carcinogenic effects of tobacco, but do not appear to be more susceptible than men to developing lung cancer. The gender differences found in female lung cancer make it mandatory that gender stratification is used in clinical trials in order to improve the survival rates of patients with lung cancer.Keywords: lung cancer, adenocarcinoma, women, genetic susceptibility, genetic differences, tobacco

Synthesis, characterization, and in vivo efficacy evaluation of PGG–docetaxel conjugate for potential cancer chemotherapy

Directory of Open Access Journals (Sweden)

Jiang X

2012-02-01

Full Text Available Danbo Yang1, Sang Van2, Yingyi Shu1, Xiaoqing Liu1, Yangfeng Ge1, Xinguo Jiang3, Yi Jin2, Lei Yu1,21Biomedical Engineering and Technology Institute, Institutes for Advanced Interdisciplinary Research, East China Normal University, Shanghai, People’s Republic of China; 2Biomedical Group, Nitto Denko Technical Corporation, CA, USA; 3School of Pharmacy, Fudan University, Shanghai, People’s Republic of ChinaAim: This work is intended to develop and evaluate a biopolymeric poly(L-γ-glutamyl-glutamine (PGG–docetaxel (DTX conjugate that can spontaneously self-assemble in aqueous solutions to become nanoparticles.Methods: DTX was covalently attached to hydrophilic PGG by direct esterification, and the conjugate was characterized by proton nuclear magnetic resonance spectroscopy, molecular weight gel permeation chromatography, solubility, size distribution and morphology, and hemolysis. Conjugated DTX was found to have 2000 times improved water solubility compared with free DTX. Dynamic light scattering, transmission electron microscopy, and atomic force microscopy revealed the particle size, distribution and morphology of the PGG–DTX conjugate. In addition, the conjugate was further tested for in vitro cytotoxicity and in vivo antitumor efficacy on the human non-small cell lung cancer cell line NCI-H460.Results: Conjugated DTX was found to have 2000 times improved water solubility compared with free DTX. The conjugate formed nanoparticles with an average diameter of 30 nm in spherical shape and unimodal particle size distribution. The conjugate exhibited about 2% hemolysis at 10 mg/mL, compared with 56% for Tween 80® at 0.4 mg/mL, and 33% for Cremophor EL® at 10 mg/mL. In addition, the conjugate was further tested for in vitro cytotoxicity and in vivo antitumor efficacy on the human non-small cell lung cancer cell line NCI-H460. As expected, conjugated DTX exhibited lower cytotoxicity compared to that of free DTX, in concentration

Proteasome inhibitors block DNA repair and radiosensitize non-small cell lung cancer.

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Kyle R Cron

Full Text Available Despite optimal radiation therapy (RT, chemotherapy and/or surgery, a majority of patients with locally advanced non-small cell lung cancer (NSCLC fail treatment. To identify novel gene targets for improved tumor control, we performed whole genome RNAi screens to identify knockdowns that most reproducibly increase NSCLC cytotoxicity. These screens identified several proteasome subunits among top hits, including the topmost hit PSMA1, a component of the core 20 S proteasome. Radiation and proteasome inhibition showed synergistic effects. Proteasome inhibition resulted in an 80-90% decrease in homologous recombination (HR, a 50% decrease in expression of NF-κB-inducible HR genes BRCA1 and FANCD2, and a reduction of BRCA1, FANCD2 and RAD51 ionizing radiation-induced foci. IκBα RNAi knockdown rescued NSCLC radioresistance. Irradiation of mice with NCI-H460 xenografts after inducible PSMA1 shRNA knockdown markedly increased murine survival compared to either treatment alone. Proteasome inhibition is a promising strategy for NSCLC radiosensitization via inhibition of NF-κB-mediated expression of Fanconi Anemia/HR DNA repair genes.

Other cancers in lung cancer families are overwhelmingly smoking-related cancers

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Hongyao Yu

2017-06-01

Full Text Available Familial risks of lung cancer are well-established, but whether lung cancer clusters with other discordant cancers is less certain, particularly beyond smoking-related sites, which may provide evidence on genetic contributions to lung cancer aetiology. We used a novel approach to search for familial associations in the Swedish Family-Cancer Database. This involved assessment of familial relative risk for cancer X in families with increasing numbers of lung cancer patients and, conversely, relative risks for lung cancer in families with increasing numbers of patients with cancers X. However, we lacked information on smoking. The total number of lung cancers in the database was 125 563. We applied stringent statistical criteria and found that seven discordant cancers were associated with lung cancer among family members, and six of these were known to be connected with smoking: oesophageal, upper aerodigestive tract, liver, cervical, kidney and urinary bladder cancers. A further novel finding was that cancer of unknown primary also associated with lung cancer. We also factored in histological evidence and found that anal and connective tissue cancers could be associated with lung cancer for reasons other than smoking. For endometrial and prostate cancers, suggestive negative associations with lung cancer were found. Although we lacked information on smoking it is prudent to conclude that practically all observed discordant associations of lung cancer were with cancers for which smoking is a risk factor.

Lung cancer-A global perspective.

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McIntyre, Amanda; Ganti, Apar Kishor

2017-04-01

Lung cancer is the leading cause of cancer deaths worldwide. While tobacco exposure is responsible for the majority of lung cancers, the incidence of lung cancer in never smokers, especially Asian women, is increasing. There is a global variation in lung cancer biology with EGFR mutations being more common in Asian patients, while Kras mutation is more common in Caucasians. This review will focus on the global variations in lung cancer and its treatment. © 2017 Wiley Periodicals, Inc.

Computed Tomography (CT) Scans and Cancer

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... Reporting & Auditing Grant Transfer Grant Closeout Contracts & Small Business Training Cancer Training at NCI (Intramural) Resources for ... companies (and Medicare) do not currently reimburse the costs of this procedure. Also, because CT ... the effectiveness of low-dose helical CT for lung cancer ...

Effect of Flavopiridol on Radiation-induced Apoptosis of Human Laryngeal and Lung Cancer Cells

International Nuclear Information System (INIS)

Kim, Suzy; Kwon, Eun Kyung; Lee, B. S.; Lee, Seung Hee; Park, B. S.; Wu, Hong Gyun

2007-01-01

Purpose: To investigate the flavopiridol effect on radiation-induced apoptosis and expression of apoptosisrelated genes of human laryngeal and lung cancer cells. Materials and Methods: A human laryngeal cancer cell line, AMC-HN3 and a human lung cancer cell line, NCI-H460, were used in the study. The cells were divided into four groups according to the type of treatment: 1) control groups; 2) cells that were only irradiated; 3) cells treated only with flavopiridol; 4) cells treated with flavopiridol and radiation simultaneously. The cells were irradiated with 10 Gy of X-rays using a 4 MV linear accelerator. Flavopiridol was administered to the media at a concentration of 100 nM for 24 hours. We compared the fraction of apoptotic cells of each group 24 hours after the initiation of treatment. The fraction of apoptotic cells was detected by measurement of the sub-G1 fractions from a flow cytometric analysis. The expression of apoptosis-regulating genes, including cleaved caspase-3, cleaved PARP (poly (ADP-ribose) polymerase), p53, p21, cyclin D1, and phosphorylated Akt (protein kinase B) were analyzed by Western blotting. Results: The sub-G1 fraction of cells was significantly increased in the combination treatment group, as compared to cells exposed to radiation alone or flavopiridol alone. Western blotting also showed an increased expression of cleaved caspase-3 and cleaved PARP expression in cells of the combination treatment group, as compared with cells exposed to radiation alone or flavopiridol alone. Treatment with flavopiridol down regulated cyclin D1 expression of both cell lines but its effect on p53 and p21 expression was different according to each individual cell line. Flavopiridol did not affect the expression of phophorylated Akt in both cell lines. Conclusion: Treatment with flavopiridol increased radiation-induced apoptosis of both the human laryngeal and lung cancer cell lines. Flavopiridol effects on p53 and p21 expression were different according

The non-coding RNAs of the H19-IGF2 imprinted loci: a focus on biological roles and therapeutic potential in Lung Cancer.

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Matouk, Imad J; Halle, David; Gilon, Michal; Hochberg, Abraham

2015-04-09

Since it was first described, the imprinted cluster 11p15.5 has been reported to be deregulated in a variety of pediatric and adult cancers including that of the lung. Both protein coding and non-coding genes functioning as oncogenes or as tumor suppressor genes reside within this cluster. Oncomirs that can function as oncogenes or as tumor suppressors have also been reported. While a complete account of the role played by the 11p15.5 imprinted cluster in lung cancer is beyond the scope of this review, we will focus on the role of the non-coding RNAs processed from the H19-IGF2 loci. A special emphasis will be given to the H19/miR-675 gene locus. Their potential diagnostic and therapeutic use in lung cancer will be described.

Monoclonal Antibody L1Mab-13 Detected Human PD-L1 in Lung Cancers.

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Yamada, Shinji; Itai, Shunsuke; Nakamura, Takuro; Yanaka, Miyuki; Chang, Yao-Wen; Suzuki, Hiroyoshi; Kaneko, Mika K; Kato, Yukinari

2018-04-01

Programmed cell death ligand-1 (PD-L1) is a type I transmembrane glycoprotein expressed on antigen-presenting cells. It is also expressed in several tumor cells such as melanoma and lung cancer cells. A strong correlation has been reported between human PD-L1 (hPD-L1) expression in tumor cells and negative prognosis in cancer patients. Here, a novel anti-hPD-L1 monoclonal antibody (mAb) L 1 Mab-13 (IgG 1 , kappa) was produced using a cell-based immunization and screening (CBIS) method. We investigated hPD-L1 expression in lung cancer using flow cytometry, Western blot, and immunohistochemical analyses. L 1 Mab-13 specifically reacted hPD-L1 of hPD-L1-overexpressed Chinese hamster ovary (CHO)-K1 cells and endogenous hPD-L1 of KMST-6 (human fibroblast) in flow cytometry and Western blot. Furthermore, L 1 Mab-13 reacted with lung cancer cell lines (EBC-1, Lu65, and Lu99) in flow cytometry and stained lung cancer tissues in a membrane-staining pattern in immunohistochemical analysis. These results indicate that a novel anti-hPD-L1 mAb, L 1 Mab-13, is very useful for detecting hPD-L1 of lung cancers in flow cytometry, Western blot, and immunohistochemical analyses.

Lung cancer - non-small cell

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Cancer - lung - non-small cell; Non-small cell lung cancer; NSCLC; Adenocarcinoma - lung; Squamous cell carcinoma - lung ... Research shows that smoking marijuana may help cancer cells grow. But there is no direct link between ...

78 FR 53763 - Proposed Collection; 60-day Comment Request Cancer Trials Support Unit (CTSU) (NCI)

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2013-08-30

... proposed data collection projects, the National Cancer Institute (NCI), National Institutes of Health (NIH), will publish periodic summaries of proposed projects to be submitted to the Office of Management and... proposed collection of information, including the validity of the methodology and assumptions used; (3...

NCI's Role in Immunotherapy Research

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... Reporting & Auditing Grant Transfer Grant Closeout Contracts & Small Business Training Cancer Training at NCI (Intramural) Resources for ... promising immunotherapies to the clinic more efficiently and cost effectively. For ... of the checkpoint inhibitor pembrolizumab in patients with ...

Lung cancer mimicking lung abscess formation on CT images.

Science.gov (United States)

Taira, Naohiro; Kawabata, Tsutomu; Gabe, Atsushi; Ichi, Takaharu; Kushi, Kazuaki; Yohena, Tomofumi; Kawasaki, Hidenori; Yamashiro, Toshimitsu; Ishikawa, Kiyoshi

2014-01-01

Male, 64 FINAL DIAGNOSIS: Lung pleomorphic carcinoma Symptoms: Cough • fever - Clinical Procedure: - Specialty: Oncology. Unusual clinical course. The diagnosis of lung cancer is often made based on computed tomography (CT) image findings if it cannot be confirmed on pathological examinations, such as bronchoscopy. However, the CT image findings of cancerous lesions are similar to those of abscesses.We herein report a case of lung cancer that resembled a lung abscess on CT. We herein describe the case of 64-year-old male who was diagnosed with lung cancer using surgery. In this case, it was quite difficult to distinguish between the lung cancer and a lung abscess on CT images, and a lung abscess was initially suspected due to symptoms, such as fever and coughing, contrast-enhanced CT image findings showing a ring-enhancing mass in the right upper lobe and the patient's laboratory test results. However, a pathological diagnosis of lung cancer was confirmed according to the results of a rapid frozen section biopsy of the lesion. This case suggests that physicians should not suspect both a lung abscesses and malignancy in cases involving masses presenting as ring-enhancing lesions on contrast-enhanced CT.

NCI Holds on to Defelice Cup | Poster

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NCI kept the Defelice Cup trophy this year after beating Leidos Biomedical Research, 15 to 9, at the 10th annual Ronald H. Defelice Golf Tournament held on Columbus Day. Sixteen players on each team battled it out at the yearly contractor vs. government tournament held at Rattlewood Golf Course in Mount Airy, Md. NCI leads the series 6–4. “The score was the highest NCI margin

Radiosensitization of C225 on human non-small cell lung cancer cell line H-520

International Nuclear Information System (INIS)

Zhang Yingdong; Wang Junjie; Liu Feng; Zhao Yong

2008-01-01

Objective: To investigate the efficacy of C225 (cetuximab), a chimeric human-mouse anti-epithelial growth factor receptor monoclonal antibody, combined with 60 Co gamma irradiation against human non-small cell lung cancer cell line H-520. Methods: H-520 cells were treated either with different dose of 60 Co irradiation (1,2,4,6,8 and 10 Gy)alone or together with C225 (100 nmol/L). Colony forming capacity was determined to create the survival curve 10 days after the treatment. Cells in different groups were harvested 72 hours after irradiation for apoptosis analysis or 48 hours after irradiation for cell cycle analysis by flow cytometry assay. Results: The clone number in combinational treatment group was less than that in irradiation only group, which suggested that the cell survival rate in the combinational treatment group was significantly decreased comparing with irradiation only group (F=6.36, P O + G 1 phases for C225 treatment, in G 2 + M phases for 60 Co irradiation, and in both G 0 + G 1 and G 2 + M phases for C225 in combination with 60 Co irradiation. Conclusions: C225 has radiosensitizing effects on H-520 cells, which may through the enhancement of 60 Co irradiation-induced cell death and cell cycle arrest. This study provides a supportive evidence for clinical treatment in non-small cell lung cancer. (authors)

Ternary copper(II) complex: NCI60 screening, toxicity studies, and evaluation of efficacy in xenograft models of nasopharyngeal carcinoma

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Chu, Tai-Lin; Abdul Aziz, Norazlin; Mohd Kornain, Noor-Kaslina; Samiulla, D. S.; Lo, Kwok-Wai; Ng, Chew-Hee

2018-01-01

Copper(II) ternary complex, [Cu(phen)(C-dmg)(H2O)]NO3 was evaluated against a panel of cell lines, tested for in vivo efficacy in nasopharyngeal carcinoma xenograft models as well as for toxicity in NOD scid gamma mice. The Cu(II) complex displayed broad spectrum cytotoxicity against multiple cancer types, including lung, colon, central nervous system, melanoma, ovarian, and prostate cancer cell lines in the NCI-60 panel. The Cu(II) complex did not cause significant induction of cytochrome P450 (CYP) 3A and 1A enzymes but moderately inhibited CYP isoforms 1A2, 2C9, 2C19, 2D6, 2B6, 2C8 and 3A4. The complex significantly inhibited tumor growth in nasopharyngeal carcinoma xenograft bearing mice models at doses which were well tolerated without causing significant or permanent toxic side effects. However, higher doses which resulted in better inhibition of tumor growth also resulted in toxicity. PMID:29329342

Iso-suillin from Suillus flavus Induces Apoptosis in Human Small Cell Lung Cancer H446 Cell Line.

Science.gov (United States)

Zhao, Jun-Xia; Zhang, Qing-Shuang; Chen, Ying; Yao, Sheng-Jie; Yan, Yong-Xin; Wang, Ying; Zhang, Jin-Xiu; Wang, Li-An

2016-05-20

The suillin isoform iso-suillin is a natural substance isolated from a petroleum ether extract of the fruiting bodies of the mushroom Suillus flavus. Previous studies have found its inhibition effect on some cancer cells, and we aimed to study its effects on human small cell lung cancer H446 cell line. Cell viability was measured by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay. Cellular morphological changes (apoptosis and necrosis) were evaluated using an electron microscope and Hoechst 33258 staining detected by the inverted microscope. Flow cytometry was used to detect cell apoptosis, cell cycle distribution, and mitochondrial membrane potential. Protein expression was determined by Western blotting analysis. Here, we describe the ability of iso-suillin to inhibit the growth of H446 cells in time- and dose-dependent way. Iso-suillin had no obvious impact on normal human lymphocyte proliferation at low concentrations (9.09, 18.17, or 36.35 μmol/L) but promoted lymphocyte proliferation at a high concentration (72.70 μmol/L). After treatment of different concentrations of iso-suillin (6.82, 13.63, or 20.45 μmol/L), the apoptosis rate of H446 cells increased with increasing concentrations of iso-suillin (16.70%, 35.54%, and 49.20%, respectively, all P iso-suillin could induce H446 cell apoptosis through the mitochondrial pathway and the death-receptor pathway. Therefore, iso-suillin might have a potential application as a novel drug for lung cancer treatment.

Osimertinib induces autophagy and apoptosis via reactive oxygen species generation in non-small cell lung cancer cells

International Nuclear Information System (INIS)

Tang, Zheng-Hai; Cao, Wen-Xiang; Su, Min-Xia; Chen, Xiuping; Lu, Jin-Jian

2017-01-01

Osimertinib (OSI), also known as AZD9291, is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that has been approved for the treatment of non-small cell lung cancer (NSCLC) patients harboring EGFR T790M mutation. Herein, we indicated for the first time that OSI increased the accumulations of cytoplasmic vacuoles, the expression of phosphatidylethanolamine-modified microtubule-associated protein light-chain 3 (LC3-II), and the formation of GFP-LC3 puncta in various cancer cells. The OSI-induced expression of LC3-II was further increased when combined treatment with chloroquine (CQ), an autophagy inhibitor, and the mRFP-EGFP-LC3 plasmid-transfected cells exposed to OSI led to the production of more red-fluorescent puncta than green-fluorescent puncta, indicating OSI induced autophagic flux in the NSCLC cells. Knockdown of EGFR showed no effect on the OSI-induced expression of LC3-II in NCI-H1975 cells. In addition, OSI increased reactive oxygen species (ROS) generation and scavenge of ROS via pretreatment with N-acetyl-L-cysteine (NAC), catalase (CAT), or vitamin E (Vita E) significantly inhibited OSI-induced the accumulations of cytoplasmic vacuoles, the expression of LC3-II, as well as the formation of GFP-LC3 puncta. Combinative treatment with CQ could not remarkably change the OSI-induced cell viability decrease, whereas the OSI-induced cell viability decrease and apoptosis could be reversed through pretreatment with NAC, CAT, and Vita E, respectively. Taken together, this is the first report that OSI induces an accompanied autophagy and the generation of ROS is critical for the OSI-induced autophagy, cell viability decrease, and apoptosis in NSCLC cells. - Highlights: • Osimertinib induced the expressions of cytoplasmic vacuoles and autophagic markers in different cancer cells. • Osimertinib induced autophagic flux in NSCLC NCI-H1975 and HCC827 cell lines. • ROS generation contributed to osimertinib-induced cytoplasmic

Osimertinib induces autophagy and apoptosis via reactive oxygen species generation in non-small cell lung cancer cells

Energy Technology Data Exchange (ETDEWEB)

Tang, Zheng-Hai; Cao, Wen-Xiang; Su, Min-Xia; Chen, Xiuping; Lu, Jin-Jian, E-mail: jinjianlu@umac.mo

2017-04-15

Osimertinib (OSI), also known as AZD9291, is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that has been approved for the treatment of non-small cell lung cancer (NSCLC) patients harboring EGFR T790M mutation. Herein, we indicated for the first time that OSI increased the accumulations of cytoplasmic vacuoles, the expression of phosphatidylethanolamine-modified microtubule-associated protein light-chain 3 (LC3-II), and the formation of GFP-LC3 puncta in various cancer cells. The OSI-induced expression of LC3-II was further increased when combined treatment with chloroquine (CQ), an autophagy inhibitor, and the mRFP-EGFP-LC3 plasmid-transfected cells exposed to OSI led to the production of more red-fluorescent puncta than green-fluorescent puncta, indicating OSI induced autophagic flux in the NSCLC cells. Knockdown of EGFR showed no effect on the OSI-induced expression of LC3-II in NCI-H1975 cells. In addition, OSI increased reactive oxygen species (ROS) generation and scavenge of ROS via pretreatment with N-acetyl-L-cysteine (NAC), catalase (CAT), or vitamin E (Vita E) significantly inhibited OSI-induced the accumulations of cytoplasmic vacuoles, the expression of LC3-II, as well as the formation of GFP-LC3 puncta. Combinative treatment with CQ could not remarkably change the OSI-induced cell viability decrease, whereas the OSI-induced cell viability decrease and apoptosis could be reversed through pretreatment with NAC, CAT, and Vita E, respectively. Taken together, this is the first report that OSI induces an accompanied autophagy and the generation of ROS is critical for the OSI-induced autophagy, cell viability decrease, and apoptosis in NSCLC cells. - Highlights: • Osimertinib induced the expressions of cytoplasmic vacuoles and autophagic markers in different cancer cells. • Osimertinib induced autophagic flux in NSCLC NCI-H1975 and HCC827 cell lines. • ROS generation contributed to osimertinib-induced cytoplasmic

Persistence of Gamma-H2AX Foci in Irradiated Bronchial Cells Correlates with Susceptibility to Radiation Associated Lung Cancer in Mice

Science.gov (United States)

Ochola, Donasian O.; Sharif, Rabab; Bedford, Joel S.; Keefe, Thomas J.; Kato, Takamitsu A.; Fallgren, Christina M.; Demant, Peter; Costes, Sylvain V.; Weil, Michael M.

2018-01-01

The risk of developing radiation-induced lung cancer differs between different strains of mice, but the underlying cause of the strain differences is unknown. Strains of mice also differ in their ability to efficiently repair DNA double strand breaks resulting from radiation exposure. We phenotyped mouse strains from the CcS/Dem recombinant congenic strain set for their efficacy in repairing DNA double strand breaks during protracted radiation exposures. We monitored persistent gamma-H2AX radiation induced foci (RIF) 24 hours after exposure to chronic gamma-rays as a surrogate marker for repair deficiency in bronchial epithelial cells for 17 of the CcS/Dem strains and the BALB/cHeN founder strain. We observed a very strong correlation R2 = 79.18%, P cancer percent incidence measured in the same strains. Interestingly, spontaneous levels of foci in non-irradiated strains also showed good correlation with lung cancer incidence (R2=32.74%, P =0.013). These results suggest that genetic differences in DNA repair capacity largely account for differing susceptibilities to radiation-induced lung cancer among CcS/Dem mouse strains and that high levels of spontaneous DNA damage is also a relatively good marker of cancer predisposition. In a smaller pilot study, we found that the repair capacity measured in peripheral blood leucocytes also correlated well with radiogenic lung cancer susceptibility, raising the possibility that such phenotyping assay could be used to detect radiogenic lung cancer susceptibility in humans.

iASPP is over-expressed in human non-small cell lung cancer and regulates the proliferation of lung cancer cells through a p53 associated pathway

International Nuclear Information System (INIS)

Chen, Jinfeng; Xie, Fei; Zhang, Lijian; Jiang, Wen G

2010-01-01

iASPP is a key inhibitor of tumour suppressor p53 and is found to be up-regulated in certain malignant conditions. The present study investigated the expression of iASPP in clinical lung cancer, a leading cancer type in the world, and the biological impact of this molecule on lung cancer cells. iASPP protein levels in lung cancer tissues were evaluated using an immunohistochemical method. In vitro, iASPP gene expression was suppressed with a lentvirus-mediated shRNA method and the biological impact after knocking down iASSP on lung cancer cell lines was investigated in connection with the p53 expression status. We showed here that the expression of iASPP was significantly higher in lung cancer tissues compared with the adjacent normal tissues. iASPP shRNA treatment resulted in a down-regulation of iASPP in lung cancer cells. There was a subsequent reduction of cell proliferation of the two lung tumour cell lines A459 and 95D both of which had wild-type p53 expression. In contrast, reduction of iASPP in H1229 cells, a cell with little p53 expression, had no impact on its growth rate. iASPP regulates the proliferation and motility of lung cancer cells. This effect is intimately associated with the p53 pathway. Together with the pattern of the over-expression in clinical lung cancers, it is concluded that iASPP plays an pivotal role in the progression of lung cancer and is a potential target for lung cancer therapy

Stages of Small Cell Lung Cancer

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... Lung Cancer Prevention Lung Cancer Screening Research Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Small Cell Lung Cancer Go to Health Professional Version Key Points Small ...

The Danish Lung Cancer Registry

DEFF Research Database (Denmark)

Jakobsen, Erik; Rasmussen, Torben Riis

2016-01-01

AIM OF DATABASE: The Danish Lung Cancer Registry (DLCR) was established by the Danish Lung Cancer Group. The primary and first goal of the DLCR was to improve survival and the overall clinical management of Danish lung cancer patients. STUDY POPULATION: All Danish primary lung cancer patients since...... 2000 are included into the registry and the database today contains information on more than 50,000 cases of lung cancer. MAIN VARIABLES: The database contains information on patient characteristics such as age, sex, diagnostic procedures, histology, tumor stage, lung function, performance...... the results are commented for local, regional, and national audits. Indicator results are supported by descriptive reports with details on diagnostics and treatment. CONCLUSION: DLCR has since its creation been used to improve the quality of treatment of lung cancer in Denmark and it is increasingly used...

Cannabis smoking and lung cancer risk: Pooled analysis in the International Lung Cancer Consortium

OpenAIRE

Zhang, L.R.; Morgenstern, H.; Greenland, S.; Chang, S.C.; Lazarus, P.; Teare, M.D.; Woll, P.J.; Orlow, I.; Cox, B.; Brhane, Y.; Liu, G.; Hung, R.J.

2015-01-01

To investigate the association between cannabis smoking and lung cancer risk, data on 2,159 lung cancer cases and 2,985 controls were pooled from 6 case-control studies in the US, Canada, UK, and New Zealand within the International Lung Cancer Consortium. Study-specific associations between cannabis smoking and lung cancer were estimated using unconditional logistic regression adjusting for sociodemographic factors, tobacco smoking status and pack-years; odds-ratio estimates were pooled usin...

Exercise and relaxation intervention for patients with advanced lung cancer

DEFF Research Database (Denmark)

Adamsen, Lis; Stage, M; Laursen, J

2012-01-01

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

Diagnostic Imaging of Lung Cancer

Directory of Open Access Journals (Sweden)

Kemal Kara

2012-12-01

Full Text Available Lung cancer is the most common cause of cancer related death in men and women. It is frequently seen among men than in women and male-female ratio is 1.5:1. Common epidemiological factors that increase risk of lung cancer is smoking. Early age to start smoking, high number of smoking cigarettes per a day and depth of inhalation increase risk of lung cancer. 25% of patients with lung cancer are nonsmokers that passively exposed to cigarette smoke. Occupational exposure to substances such as asbestos, arsenic, nickel, beryllium, mustard gas increases the risk of lung cancer. The well defined risk factor is exposure to asbestos. In addition advanced age, diffuse pulmonary fibrosis, chronic obstructive pulmonary disease (COPD and genetic predisposition are the risk factors that increases lung cancer. [TAF Prev Med Bull 2012; 11(6.000: 749-756

Attitudes and Stereotypes in Lung Cancer versus Breast Cancer.

Directory of Open Access Journals (Sweden)

N Sriram

Full Text Available Societal perceptions may factor into the high rates of nontreatment in patients with lung cancer. To determine whether bias exists toward lung cancer, a study using the Implicit Association Test method of inferring subconscious attitudes and stereotypes from participant reaction times to visual cues was initiated. Participants were primarily recruited from an online survey panel based on US census data. Explicit attitudes regarding lung and breast cancer were derived from participants' ratings (n = 1778 regarding what they thought patients experienced in terms of guilt, shame, and hope (descriptive statements and from participants' opinions regarding whether patients ought to experience such feelings (normative statements. Participants' responses to descriptive and normative statements about lung cancer were compared with responses to statements about breast cancer. Analyses of responses revealed that the participants were more likely to agree with negative descriptive and normative statements about lung cancer than breast cancer (P<0.001. Furthermore, participants had significantly stronger implicit negative associations with lung cancer compared with breast cancer; mean response times in the lung cancer/negative conditions were significantly shorter than in the lung cancer/positive conditions (P<0.001. Patients, caregivers, healthcare providers, and members of the general public had comparable levels of negative implicit attitudes toward lung cancer. These results show that lung cancer was stigmatized by patients, caregivers, healthcare professionals, and the general public. Further research is needed to investigate whether implicit and explicit attitudes and stereotypes affect patient care.

Correlation between atopic manifestation and lung toxicity following chest irradiation for breast cancer

International Nuclear Information System (INIS)

Hirota, Saeko; Shimizu, Tadafumi; Kubota, Satoshi

2007-01-01

The purpose of this study was to identify the impact of atopic manifestations on the occurrence of the lung toxicity following chest irradiation for breast cancer. Collection of 1,173 patients who had undergone radiotherapy on their 1,177 chest walls or postsurgical mammary glands at 9 institutions including ours. They received treatment consecutively from December 1980 through October 2005, with which we formed the basis of this analysis. Patients with any of the following medical history were defined as having atopic manifestations (n=111): asthma, allergic rhinitis, atopic dermatitis, contact dermatitis, and allergy to food or drug. Of them, patients who were observed for at least 6 months or who suffered from lung toxicity at any time, were classified as Group A (n=85). On the other hand, patients in our institute who were observed for at least 6 months or who suffered from lung toxicity at any time regardless of atopic manifestations, were classified as Group B (n=113), and patients without any atopic manifestation were classified as Group C (n=92). Grade 3 or higher lung toxicity in National Cancer Institute, Common Toxicity Criteria for Adverse Events (NCI-CTCAE) (v 3.0), occurred in 8.2%, id est (i.e.) 7 cases, of Group A, 2.7% of Group B, and 1.1% of Group C (p=0.0293 Group C against Group A). Three cases were classified as classical pneumonitis, and the other 4 sporadic pneumonitis such as Cryptogenic Organizing Pneumonia and Chronic Eosinophilic Pneumonia. Both of the histologically proven COP and CEP patients showed atopic manifestations in our institute. The detail clinical features are described in the main text. Having atopic manifestations suggests that there may be risk of lung toxicity following chest irradiation for breast cancer. (author)

Globo H expression is associated with driver mutations and PD-L1 expressions in stage I non-small cell lung cancer.

Science.gov (United States)

Yang, Ching-Yao; Lin, Mong-Wei; Chang, Yih-Leong; Wu, Chen-Tu

2017-12-12

Globo H is a tumor-associated carbohydrate antigen exclusively expressed in cancer cells rather than normal tissue. Globo H has been found on many cancers of epithelial origins, and become an attractive target for cancer vaccine. We aimed to study the expression of Globo H in non-small cell lung cancer (NSCLC) patients, and correlated its expression with common driver mutations, clinical outcomes, and status of immune checkpoint, programmed death-ligand 1 (PD-L1). The study enrolled 228 patients with surgically resected stage I NSCLC, including 139 patients with adenocarcinoma (ADC) and 89 patients with squamous cell carcinoma (SqCC). Using immunohistochemistry, tumors with moderate to strong membranous staining in ⩾ 1% tumor cells per section were scored as positive Globo H expression. Driver mutations including EGFR, KRAS, BRAF were detected by direct sequencing, while ALK, PI3KCA, FGFR1 and PD-L1 expression was detected by immunohistochemical (IHC) staining. Positive Globo H expression was detected in 88 of the 228 (38.6%) patients. These included 51 of 139 (36.7%) patients with ADC and 37 of 89 (41.6%) patients with SqCC. Positive Globo H expression was significantly associated with EGFR mutation and PD-L1 expression in the ADC group, and PI3KCA overexpression in the SqCC group. The survival analysis showed that Globo H expression was not an independent prognostic factor in stage I NSCLC. Globo H expression was correlated with specific driver mutations in ADC and SqCC NSCLC tumors, as well as PD-L1 status. Immunotherapy targeting Globo H may have potential application in lung cancer treatment.

Discrepancy of biologic behavior influenced by bone marrow derived cells in lung cancer.

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Zhang, Jie; Niu, Xiao-Min; Liao, Mei-Lin; Liu, Yun; Sha, Hui-Fang; Zhao, Yi; Yu, Yong-Feng; Tan, Qiang; Xiang, Jia-Qing; Fang, Jing; Lv, Dan-Dan; Li, Xue-Bing; Lu, Shun; Chen, Hai-Quan

2010-11-01

Disseminated cancer cells may initially require local nutrients and growth factors to thrive and survive in bone marrow. However, data on the influence of bone marrow derived cells (BMDC, also called bone stromal cells in some publications) on lung cancer cells is largely unexplored. This study explored the mechanism of how bone stromal factors contribute to the bone tropism in lung cancer. The difference among lung cancer cell lines in their abilities to metastasize to bone was found using the SCID animal model. Supernatant of bone marrow aspiration (BM) and condition medium from human bone stromal cells (BSC) were used to study the activity of bone stromal factors. We found bone stromal factors significantly increased the proliferation, invasion, adhesion and expression of angiogenosis-related factors, and inhibited the apoptosis for high bone metastasis H460 lung cancer cells. These biologic effects were not seen in SPC-A1 or A549 cells, which are low bone metastasis lung cancer cells. Adhesion of H460 cells to surface coated with bone stromal cells can activate some signal transduction pathways, and alter the expression of adhesion associated factors, including integrin β 3 and ADAMTS-1, two potential targets related with bone metastasis. We concluded that bone marrow derived cells had a profound effect on biological behavior of lung cancers, therefore favoring the growth of lung cancer cells in bone.

Lung Cancer Indicators Recurrence

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This study describes prognostic factors for lung cancer spread and recurrence, as well as subsequent risk of death from the disease. The investigators observed that regardless of cancer stage, grade, or type of lung cancer, patients in the study were more

Telomerase in lung cancer diagnostics

International Nuclear Information System (INIS)

Kovkarova, E.; Stefanovski, T.; Dimov, A.; Naumovski, J.

2003-01-01

Background. Telomerase is a ribonucleoprotein that looks after the telomeric cap of the linear chromosomes maintaining its length. It is over expressed in tumour tissues, but not in normal somatic cells. Therefore the aim of this study was to determine the telomerase activity in lung cancer patients as novel marker for lung cancer detection evaluating the influence of tissue/cell obtaining technique. Material and methods. Using the TRAP (telomeric repeat amplification protocol), telomerase activity was determined in material obtained from bronchobiopsy (60 lung cancer patients compared with 20 controls) and washings from transthoracic fine needle aspiration biopsy performed in 10 patients with peripheral lung tumours. Results. Telomerase activity was detected in 75% of the lung cancer bronchobyopsies, and in 100% in transthoracic needle washings. Conclusions. Measurement of telomerase activity can contribute in fulfilling the diagnosis of lung masses and nodules suspected for lung cancer. (author)

Plant collecting program in Southeast Asia under the sponsorship of the United States National Cancer Institute (NCI) (1986-1991)

NARCIS (Netherlands)

Soejarto, D.D.

1992-01-01

Under the funding from the United States National Cancer Institute (NCI)¹, a program was undertaken to collect plant samples in Southeast Asia to be tested for their cancer- and AIDS-arresting properties, for the period of September 1, 1986 through August 31, 1991. The program was implemented with

Lung cancer in younger patients

DEFF Research Database (Denmark)

Abbasowa, Leda; Madsen, Poul Henning

2016-01-01

INTRODUCTION: Lung cancer remains a leading cause of cancer-related death. The incidence increases with age and the occurrence in young patients is relatively low. The clinicopathological features of lung cancer in younger patients have not been fully explored previously. METHODS: To assess the age...... differences in the clinical characteristics of lung cancer, we conducted a retrospective analysis comparing young patients ≤ 65 years of age with an elderly group > 65 years of age. Among 1,232 patients evaluated due to suspicion of lung cancer in our fast-track setting from January-December 2013, 312 newly...... diagnosed lung cancer patients were included. RESULTS: Patients ≤ 65 years had a significantly higher representation of females (p = 0.0021), more frequent familial cancer aggregation (p = 0.028) and a lower incidence of squamous cell carcinoma (p = 0.0133). When excluding pure carcinoid tumours...

Targeting apoptosis pathways in lung cancer

NARCIS (Netherlands)

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

2013-01-01

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

Increased mean lung density: Another independent predictor of lung cancer?

Energy Technology Data Exchange (ETDEWEB)

Sverzellati, Nicola, E-mail: nicola.sverzellati@unipr.it [Department of Department of Surgical Sciences, Section of Diagnostic Imaging, University of Parma, Padiglione Barbieri, University Hospital of Parma, V. Gramsci 14, 43100 Parma (Italy); Randi, Giorgia, E-mail: giorgia.randi@marionegri.it [Department of Epidemiology, Mario Negri Institute, Via La Masa 19, 20156 Milan (Italy); Spagnolo, Paolo, E-mail: paolo.spagnolo@unimore.it [Respiratory Disease Unit, Center for Rare Lung Disease, Department of Oncology, Hematology and Respiratory Disease, University of Modena and Reggio Emilia, Via del Pozzo 71, 44124 Modena (Italy); Marchianò, Alfonso, E-mail: alfonso.marchiano@istitutotumori.mi.it [Department of Radiology, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan (Italy); Silva, Mario, E-mail: mac.mario@hotmail.it [Department of Department of Surgical Sciences, Section of Diagnostic Imaging, University of Parma, Padiglione Barbieri, University Hospital of Parma, V. Gramsci 14, 43100 Parma (Italy); Kuhnigk, Jan-Martin, E-mail: Jan-Martin.Kuhnigk@mevis.fraunhofer.de [Fraunhofer MEVIS, Universitaetsallee 29, 28359 Bremen (Germany); La Vecchia, Carlo, E-mail: carlo.lavecchia@marionegri.it [Department of Occupational Health, University of Milan, Via Venezian 1, 20133 Milan (Italy); Zompatori, Maurizio, E-mail: maurizio.zompatori@unibo.it [Department of Radiology, Cardio-Thoracic Section, S. Orsola-Malpighi Hospital, Via Albertoni 15, 40138 Bologna (Italy); Pastorino, Ugo, E-mail: ugo.pastorino@istitutotumori.mi.it [Department of Surgery, Section of Thoracic Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan (Italy)

2013-08-15

Objectives: To investigate the relationship between emphysema phenotype, mean lung density (MLD), lung function and lung cancer by using an automated multiple feature analysis tool on thin-section computed tomography (CT) data. Methods: Both emphysema phenotype and MLD evaluated by automated quantitative CT analysis were compared between outpatients and screening participants with lung cancer (n = 119) and controls (n = 989). Emphysema phenotype was defined by assessing features such as extent, distribution on core/peel of the lung and hole size. Adjusted multiple logistic regression models were used to evaluate independent associations of CT densitometric measurements and pulmonary function test (PFT) with lung cancer risk. Results: No emphysema feature was associated with lung cancer. Lung cancer risk increased with decreasing values of forced expiratory volume in 1 s (FEV{sub 1}) independently of MLD (OR 5.37, 95% CI: 2.63–10.97 for FEV{sub 1} < 60% vs. FEV{sub 1} ≥ 90%), and with increasing MLD independently of FEV{sub 1} (OR 3.00, 95% CI: 1.60–5.63 for MLD > −823 vs. MLD < −857 Hounsfield units). Conclusion: Emphysema per se was not associated with lung cancer whereas decreased FEV{sub 1} was confirmed as being a strong and independent risk factor. The cross-sectional association between increased MLD and lung cancer requires future validations.

Axin gene methylation status correlates with radiosensitivity of lung cancer cells

International Nuclear Information System (INIS)

Yang, Lian-He; Stoecker, Maggie; Wang, Endi; Xu, Ke; Wang, En-Hua; Han, Yang; Li, Guang; Xu, Hong-Tao; Jiang, Gui-Yang; Miao, Yuan; Zhang, Xiu-Peng; Zhao, Huan-Yu; Xu, Zheng-Fan

2013-01-01

We previously reported that Axin1 (Axin) is down-regulated in many cases of lung cancer, and X-ray irradiation increased Axin expression and inhibited lung cancer cells. The mechanisms, however, were not clear. Four lung cancer cell lines were used to detect the methylation status of Axin with or without X-ray treatment. Real-time PCR was used to quantify the expression of Axin, and western blot analysis was applied to measure protein levels of Axin, β-catenin, Cyclin D1, MMP-7, DNMTS, MeCP2 and acetylated histones. Flow cytometric analysis, colony formation assay, transwell assay and xenograft growth experiment were used to study the biological behavior of the cells with hypermethylated or unmethylated Axin gene after X-ray treatment. Hypermethylated Axin gene was detected in 2 of 4 cell lines, and it correlated inversely with Axin expression. X-ray treatment significantly up-regulated Axin expression in H446 and H157 cells, which possess intrinsic hypermethylation of the Axin gene (P<0.01), but did not show up-regulation in LTE and H460 cells, which have unmethylated Axin gene. 2Gy X-ray significantly reduced colony formation (from 71% to 10.5%) in H157 cells, while the reduction was lower in LTE cells (from 71% to 20%). After X-ray irradiation, xenograft growth was significantly decreased in H157 cells (from 1.15 g to 0.28 g) in comparison with LTE cells (from 1.06 g to 0.65 g). Significantly decreased cell invasiveness and increased apoptosis were also observed in H157 cells treated with X-ray irradiation (P<0.01). Down-regulation of DNMTs and MeCP2 and up-regulation of acetylated histones could be detected in lung cancer cells. X-ray-induced inhibition of lung cancer cells may be mediated by enhanced expression of Axin via genomic DNA demethylation and histone acetylation. Lung cancer cells with a different methylation status of the Axin gene showed different radiosensitivity, suggesting that the methylation status of the Axin gene may be one important factor

Rare lung cancers

International Nuclear Information System (INIS)

Berzinec, P.

2013-01-01

The RARECARE Project (Rare Cancers in the Europe) supported by the European Union defined the rare cancers by the incidence rate of less than 6/100 000. There are several variants of lung cancer which are rare according to this definition. From the clinical point of view the most interesting are the rare adenocarcinomas and large cell neuroendocrine carcinoma. There are important differences in the diagnostic probability of EGFR and ALK mutations in the mutinous and non-mucin ous adenocarcinomas, in the signet ring cell adenocarcinomas, and large cell carcinomas. The optimal chemotherapy for neuroendocrine large cell carcinomas remains undefined. There is only very limited number of clinical trials aimed on the rare lung cancers and actually none phase III trial. Rare lung cancers continue to be a challenge both for the laboratory and the clinical research. (author)

Lung Cancer in uranium miners

International Nuclear Information System (INIS)

Zhou Chundi; Fan Jixiong; Wang Liuhu; Huang Yiehan; Nie Guanghua

1987-01-01

This paper analyese the clinical data of 39 uranium miners with lung cancer and of 20 patients with lung cancer who have not been exposed to uranium as control. The age of uranium miners with lung cancer was 36∼61 with an average of 48.8, nine years earlier than that of the control group (57.3). In the uranium miner patients the right lung was more susceptible to cancer than the left, the ratio being 2.5:1. However, in the control group the right lung had an equal incidence of cancer as the left lung. The relative frequency of small cell anaplastic carcinoma in uranium miner was higher than that in the control group. In the miner patients the mean occupation history was 11.1 ± 5.2 years; the exposure dose to radon and its daughters in 50% patients was 0.504J(120 WLM). The etiologic factor of lung cancer in uranium miners is strongly attributed, in addition to smoking, to the exposure to radon and its daughters in uranium mines

Multi-Modal Imaging in a Mouse Model of Orthotopic Lung Cancer

OpenAIRE

Patel, Priya; Kato, Tatsuya; Ujiie, Hideki; Wada, Hironobu; Lee, Daiyoon; Hu, Hsin-pei; Hirohashi, Kentaro; Ahn, Jin Young; Zheng, Jinzi; Yasufuku, Kazuhiro

2016-01-01

Background Investigation of CF800, a novel PEGylated nano-liposomal imaging agent containing indocyanine green (ICG) and iohexol, for real-time near infrared (NIR) fluorescence and computed tomography (CT) image-guided surgery in an orthotopic lung cancer model in nude mice. Methods CF800 was intravenously administered into 13 mice bearing the H460 orthotopic human lung cancer. At 48 h post-injection (peak imaging agent accumulation time point), ex vivo NIR and CT imaging was performed. A cli...

The generalizability of NCI-sponsored clinical trials accrual among women with gynecologic malignancies.

Science.gov (United States)

Mishkin, Grace; Minasian, Lori M; Kohn, Elise C; Noone, Anne-Michelle; Temkin, Sarah M

2016-12-01

Enrollment of a representative population to cancer clinical trials ensures scientific reliability and generalizability of results. This study evaluated the similarity of patients enrolled in NCI-supported group gynecologic cancer trials to the incident US population. Accrual to NCI-sponsored ovarian, uterine, and cervical cancer treatment trials between 2003 and 2012 were examined. Race, ethnicity, age, and insurance status were compared to the analogous US patient population estimated using adjusted SEER incidence data. There were 18,913 accruals to 156 NCI-sponsored gynecologic cancer treatment trials, ovarian (56%), uterine (32%), and cervical cancers (12%). Ovarian cancer trials included the least racial, ethnic and age diversity. Black women were notably underrepresented in ovarian trials (4% versus 11%). Hispanic patients were underrepresented in ovarian and uterine trials (4% and 5% versus 18% and 19%, respectively), but not in cervical cancer trials (14 versus 11%). Elderly patients were underrepresented in each disease area, with the greatest underrepresentation seen in ovarian cancer patients over the age of 75 (7% versus 29%). Privately insured women were overrepresented among accrued ovarian cancer patients (87% versus 76%), and the uninsured were overrepresented among women with uterine or cervical cancers. These patterns did not change over time. Several notable differences were observed between the patients accrued to NCI funded trials and the incident population. Improving representation of racial and ethnic minorities and elderly patients on cancer clinical trials continues to be a challenge and priority. Copyright © 2016 Elsevier Inc. All rights reserved.

Selected Publications by the NCI Director

Science.gov (United States)

Dr. Norman Sharpless's written work on cancer research appears in many leading scientific journals, as well as a variety of other publications. This page lists some of the articles published by Dr. Sharpless since becoming NCI director.

ERK phosphorylation is predictive of resistance to IGF-1R inhibition in small cell lung cancer.

Science.gov (United States)

Zinn, Rebekah L; Gardner, Eric E; Marchionni, Luigi; Murphy, Sara C; Dobromilskaya, Irina; Hann, Christine L; Rudin, Charles M

2013-06-01

New therapies are critically needed to improve the outcome for patients with small cell lung cancer (SCLC). Insulin-like growth factor 1 receptor (IGF-1R) inhibition is a potential treatment strategy for SCLC: the IGF-1R pathway is commonly upregulated in SCLC and has been associated with inhibition of apoptosis and stimulation of proliferation through downstream signaling pathways, including phosphatidylinositol-3-kinase-Akt and mitogen-activated protein kinase. To evaluate potential determinants of response to IGF-1R inhibition, we assessed the relative sensitivity of 19 SCLC cell lines to OSI-906, a small molecule inhibitor of IGF-1R, and the closely related insulin receptor. Approximately one third of these cell lines were sensitive to OSI-906, with an IC50 OSI-906. Interestingly, OSI-906 sensitive lines expressed significantly lower levels of baseline phospho-ERK relative to resistant lines (P = 0.006). OSI-906 treatment resulted in dose-dependent inhibition of phospho-IGF-1R and phospho-Akt in both sensitive and resistant cell lines, but induced apoptosis and cell-cycle arrest only in sensitive lines. We tested the in vivo efficacy of OSI-906 using an NCI-H187 xenograft model and two SCLC patient xenografts in mice. OSI-906 treatment resulted in 50% tumor growth inhibition in NCI-H187 and 30% inhibition in the primary patient xenograft models compared with mock-treated animals. Taken together our data support IGF-1R inhibition as a viable treatment strategy for a defined subset of SCLC and suggest that low pretreatment levels of phospho-ERK may be indicative of sensitivity to this therapeutic approach. ©2013 AACR

THE NCI STUDIES ON RADIATION DOSES AND CANCER RISKS IN THE MARSHALL ISLANDS ASSOCIATED WITH EXPOSURE TO RADIOACTIVE FALLOUT

OpenAIRE

Simon, Steven L.

2012-01-01

The U.S. National Cancer Institute (NCI, National Institutes of Health) was requested by the U.S. Congress in 2004 to assess the number of radiation-related illnesses to be expected among the people of the Marshall Islands from nuclear tests conducted there during 1946-1958. A thorough analysis conducted by the NCI concluded that 20 of the 66 nuclear devices tested in or near the Marshall Islands resulted in measurable fallout deposition on one or more of the inhabited atolls of the Marshall ...

General Information about Small Cell Lung Cancer

Science.gov (United States)

... Lung Cancer Prevention Lung Cancer Screening Research Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Small Cell Lung Cancer Go to Health Professional Version Key Points Small ...

Effects of Src on Proliferation and Invasion of Lung Cancer Cells

Directory of Open Access Journals (Sweden)

Rui ZHENG

2011-04-01

Full Text Available Background and objective It has been proven that Src played pivotal roles in carcinogenesis, cancer progression and metastasis. The aim of this study is to explore the roles of Src phosphorylation on lung cancer cells. Methods Western blot and immunoprecipitation was used to detect the expression and phosphorylation of Src in lung cancer cells. MTT and Boyden chamber assay was used to examine the effects of inhibition of Src phosphorylation on proliferation and invasion of lung cancer cells in vitro, respectively. Results pp60src was expressed in all lung cancer cell lines in this study. All 5 non-small cell lung cancer (NSCLC cell lines had increased autophosphorylated tyrosine-418, while nearly no phosphorylated Src in small cell lung cancer SBC5 cell line was detected. The effect of inhibition of Src tyrosine kinase on cell proliferation varied among the lung cancer cell lines. Submicromolar Src tyrosine kinase inhibitor (≤1 μM remarkably suppressed the proliferation of PC-9 and A549 cells in a dose dependent manner (P < 0.05, while the same concentration of Src tyrosine kinase inhibitor had no significant effect on proliferation of H226, PC14PE6 and RERFLCOK cells. Invasiveness of lung cancer cells was significantly suppressed by Src tyrosine kinase in a dose-dependent manner (P < 0.05. Conclusion Phosphorylation of Src, but not over-expression, plays a pivotal role in proliferation and invasion of NSCLC cell lines in vitro.

Radon exposure and lung cancer

International Nuclear Information System (INIS)

Planinic, J.; Vukovic, B.; Faj, Z.; Radolic, V.; Suveljak, B.

2003-01-01

Although studies of radon exposure have established that Rn decay products are a cause of lung cancer among miners, the lung cancer risk to the general population from indoor radon remains unclear and controversial. Our epidemiological investigation of indoor radon influence on lung cancer incidence was carried out for 201 patients from the Osijek town. Ecological method was applied by using the town map with square fields of 1 km 2 and the town was divided into 24 fields. Multiple regression study for the lung cancer rate on field, average indoor radon exposure and smoking showed a positive linear double regression for the mentioned variables. Case-control study showed that patients, diseased of lung cancer, dwelt in homes with significantly higher radon concentrations, by comparison to the average indoor radon level of control sample. (author)

A standardized bark extract of Pinus pinaster Aiton (Pycnogenol®) attenuated chronic obstructive pulmonary disease via Erk-sp1 signaling pathway.

Science.gov (United States)

Shin, Na-Rae; Ryu, Hyung-Won; Ko, Je-Won; Park, Ji-Won; Kwon, Ok-Kyoung; Oh, Sei-Ryang; Kim, Jong-Choon; Shin, In-Sik; Ahn, Kyung-Seop

2016-12-24

A standardized bark extract of Pinus pinaster Aiton (Pycnogenol ® ; PYC) used as an herbal medicine to treat various diseases in Europe and North America. This study evaluates the ability of PYC to inhibit chronic obstructive pulmonary disease (COPD) in the cigarette smoke extract (CSE)-stimulated human airway epithelial cell line NCI-H292 and in a cigarette smoke (CS) and lipopolysaccharide (LPS)-induced mouse model. To induce COPD, the mice intranasally received LPS on day 4 and were exposed to CS for 1h per day (total eight cigarettes per day) from days 1-7. The mice were administered PYC at a dose of 15mg/kg and 30mg/kg 1h before CS exposure. In the CSE-stimulated NCI-H292 cells, PYC significantly inhibited Erk phosphorylation, sp1 expression, MUC5AC, and pro-inflammatory cytokines in a concentration-dependent manner, as evidenced by a reduction in their mRNA levels. Co-treatment with PYC and Erk inhibitors markedly reduced the levels inflammatory mediators compared to only PYC-treatment. In the COPD mice model, PYC decreased the inflammatory cell count and the levels of pro-inflammatory cytokines in the broncho-alveolar lavage fluid compared with COPD mice. PYC attenuated the recruitment of inflammatory cells in the airways and decreased the expression levels of Erk phosphorylation and sp1. PYC also inhibited the expression of myeloperoxidase and matrix metalloproteinases-9 in lung tissue. Our results indicate that PYC inhibited the reduction in the inflammatory response in CSE-stimulated NCI-H292 cells and the COPD mouse model via the Erk-sp1 pathway. Therefore, we suggest that PYC has the potential to treat COPD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Gamma-aminobutyric acid, a potential tumor suppressor for small airway-derived lung adenocarcinoma.

Science.gov (United States)

Schuller, Hildegard M; Al-Wadei, Hussein A N; Majidi, Mourad

2008-10-01

Pulmonary adenocarcinoma (PAC) is the leading type of lung cancer in smokers and non-smokers that arises in most cases from small airway epithelial cells. PAC has a high mortality due to its aggressive behavior and resistance to cancer therapeutics. We have shown previously that the proliferation of human PAC cells NCI-H322 and immortalized human small airway epithelial cells HPL1D is stimulated by cyclic adenosine monophosphate (cAMP)/protein kinase A-dependent phosphorylation of cyclic adenosine monophosphate response element-binding (CREB) protein and transactivation of the epidermal growth factor receptor and that this pathway is activated by beta-1-adrenoreceptors (beta(1)-ARs) and the non-genomic estrogen receptor beta. Our current in vitro studies with HPL1D and NCI-H322 cells showed that signaling via the gamma-amino butyric acid receptor (GABA(B)R) strongly inhibited base level and isoproterenol-induced cAMP, p-CREB, cyclic adenosine monophosphate response element-luciferase activity and p-extracellular regulated kinase-1 (ERK1)/2 and effectively blocked DNA synthesis and cell migration. The inhibitory effects of gamma-amino butyric acid (GABA) were disinhibited by the GABA(B)R antagonist CGP-35348 or GABA(B)R knockdown. Immunohistochemical investigation of hamster lungs showed significant underexpression of GABA in animals with small airway-derived PACs induced by the nicotine-derived carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). These findings suggest that GABA may have tumor suppressor function in small airway epithelia and the PACs derived from them and that downregulation of GABA by NNK may contribute to the development of this cancer in smokers. Our findings suggest that marker-guided treatment with GABA or a GABA(B)R agonist of individuals with downregulated pulmonary GABA may provide a novel targeted approach for the prevention of PAC in smokers.

Antiapoptotic effects of caspase inhibitors on H2O2-treated lung cancer cells concerning oxidative stress and GSH.

Science.gov (United States)

Park, Woo Hyun

2018-04-01

Exogenous hydrogen peroxide (H 2 O 2 ) induces oxidative stress and apoptosis in cancer cells. This study evaluated the antiapoptotic effects of pan-caspase and caspase-3, -8, or -9 inhibitors on H 2 O 2 -treated Calu-6 and A549 lung cancer cells in relation to reactive oxygen species (ROS) and glutathione (GSH). Treatment with 50-500 μM H 2 O 2 inhibited the growth of Calu-6 and A549 cells at 24 h and induced apoptosis in these cells. All the tested caspase inhibitors significantly prevented cell death in H 2 O 2 -treated lung cancer cells. H 2 O 2 increased intracellular ROS levels, including that of O 2 ·- , at 1 and 24 h. It also increased the activity of catalase but decreased the activity of SOD. In addition, H 2 O 2 triggered GSH deletion in Calu-6 and A549 cells at 24 h. It reduced GSH levels in Calu-6 cells at 1 h but increased them at 24 h. Caspase inhibitors decreased O 2 ·- levels in H 2 O 2 -treated Calu-6 cells at 1 h and these inhibitors decreased ROS levels, including that of O 2 ·- , in H 2 O 2 -treated A549 cells at 24 h. Caspase inhibitors partially attenuated GSH depletion in H 2 O 2 -treated A549 cells and increased GSH levels in these cells at 24 h. However, the inhibitors did not affect GSH deletion and levels in Calu-6 cells at 24 h. In conclusion, H 2 O 2 induced caspase-dependent apoptosis in Calu-6 and A549 cells, which was accompanied by increases in ROS and GSH depletion. The antiapoptotic effects of caspase inhibitors were somewhat related to the suppression of H 2 O 2 -induced oxidative stress and GSH depletion.

Durvalumab: a potential maintenance therapy in surgery-ineligible non-small-cell lung cancer

Directory of Open Access Journals (Sweden)

Shafique MR

2018-05-01

Full Text Available Michael R Shafique, Lary A Robinson, Scott Antonia Department of Thoracic Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA Abstract: Lung cancer is the most common cancer worldwide and the most common cause of cancer-related death. Non-small-cell lung cancer comprises ~87% of newly diagnosed cases of lung cancer, and nearly one-third of these patients have stage III disease. Despite improvements in the treatment of stage IV lung cancer, particularly with the introduction and dissemination of checkpoint inhibitors, very little progress has been made in the treatment of stage III lung cancer. In this article, we discuss the general staging criteria and treatment options for stage III lung cancer. We review how concurrent radiation and chemotherapy can have immunomodulatory effects, supporting the rationale for incorporating immunotherapy into existing treatment paradigms. Finally, we discuss the results of the PACIFIC trial and implications for the treatment of stage III lung cancer. In the PACIFIC trial, adding durvalumab as a maintenance therapy following the completion of chemoradiotherapy improved progression-free survival in patients with locally advanced unresectable stage III lung cancer. On the strength of these results, durvalumab has been approved by the US Food and Drug Administration for use in this setting, representing the first advance in the treatment of stage III lung cancer in nearly a decade. Keywords: non-small-cell lung cancer, maintenance therapy, staging, immunotherapy, chemoradiation, surgery-ineligible, durvalumab

Life Outside NCI | Cancer Prevention Fellowship Program

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The CPFP Office is located at the NCI facilities in Rockville, Maryland, near the Nation’s Capital. With the convenient Metro subway reaching throughout the metropolitan area, transportation is within easy reach.

Improving clinical research and cancer care delivery in community settings: evaluating the NCI community cancer centers program.

Science.gov (United States)

Clauser, Steven B; Johnson, Maureen R; O'Brien, Donna M; Beveridge, Joy M; Fennell, Mary L; Kaluzny, Arnold D

2009-09-26

In this article, we describe the National Cancer Institute (NCI) Community Cancer Centers Program (NCCCP) pilot and the evaluation designed to assess its role, function, and relevance to the NCI's research mission. In doing so, we describe the evolution of and rationale for the NCCCP concept, participating sites' characteristics, its multi-faceted aims to enhance clinical research and quality of care in community settings, and the role of strategic partnerships, both within and outside of the NCCCP network, in achieving program objectives. The evaluation of the NCCCP is conceptualized as a mixed method multi-layered assessment of organizational innovation and performance which includes mapping the evolution of site development as a means of understanding the inter- and intra-organizational change in the pilot, and the application of specific evaluation metrics for assessing the implementation, operations, and performance of the NCCCP pilot. The assessment of the cost of the pilot as an additional means of informing the longer-term feasibility and sustainability of the program is also discussed. The NCCCP is a major systems-level set of organizational innovations to enhance clinical research and care delivery in diverse communities across the United States. Assessment of the extent to which the program achieves its aims will depend on a full understanding of how individual, organizational, and environmental factors align (or fail to align) to achieve these improvements, and at what cost.

Cannonball lung metastases as a presenting feature of ectopic hCG expression

Directory of Open Access Journals (Sweden)

Rong-Hsin Yang

2016-08-01

Full Text Available Cannonball metastases refer to well-defined spherical nodules scattered over both lungs, being a classical presentation of hematogenous tumor spreading. Striking progression of lung metastases without established primary malignancy can raise a diagnostic challenge. We herein report three cases with cannonball metastases at initial presentation. Two patients ended up having a choriocarcinoma but no awareness of the presence of primary tumors, and the third had abrupt lung metastases of endometrial cancer while she was being asymptomatic. Relentless progression was illustrated by clinical and radiographic changes. Ectopic expression of human chorionic gonadotropin (hCG would seemingly go some way responsible for fulminant cancer spreading associated with poor prognosis in our patients. The goal of this presentation is to raise awareness of ectopic hCG expression in patients presenting with similar astonishing scenarios.

Effect of BRCA1 on radiosensitivity of different lung cancer cells

International Nuclear Information System (INIS)

Zhang Huiwen; Wang Miao; Wang Yansu; Ren Hang; Xu Jiaying; Jiao Yang; Fan Saijun; Meng Qinghui

2011-01-01

Objective: To investigate the effects BRCA1 on sensitivity of lung cancer cells to γ-irradiation. Methods: A mammalian expression pcDNA3 vectors encoding a full-length of BRCA1 cDNA and BRCA1 siRNA were transfected into lung cancer cells. Western blot, MTT and clonogenic assays were used to determine BRCA1 protein expression and cell survival following γ-irradiation respectively. Results: There is a close relationship between BRCA1 level and radiosensitivity in different lung cancer cell lines. Compared with the control cells transfected with the 'empty' pcDNA3 vector and parental cells, the more survival of cells transfected with BRCA1 was observed after irradiation. The BRCA1-caused radioresistance were observed in both A549 and HTB-58 lung cancer lines. However, NIH-H2170 cells transfected with BRCA1 siRNA became more sensitive to γ-irradiation. Conclusion: This study, for the first time, demonstrates that the alteration of BRCA1 expression significantly affects radiosensitivity of lung cancer, indicating that BRCA1 may be an important mediator in radiotherapy of lung cancer cells. (authors)

Estrogen, Estrogen Receptor and Lung Cancer

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Li-Han Hsu

2017-08-01

Full Text Available Estrogen has been postulated as a contributor for lung cancer development and progression. We reviewed the current knowledge about the expression and prognostic implications of the estrogen receptors (ER in lung cancer, the effect and signaling pathway of estrogen on lung cancer, the hormone replacement therapy and lung cancer risk and survival, the mechanistic relationship between the ER and the epidermal growth factor receptor (EGFR, and the relevant clinical trials combining the ER antagonist and the EGFR antagonist, to investigate the role of estrogen in lung cancer. Estrogen and its receptor have the potential to become a prognosticator and a therapeutic target in lung cancer. On the other hand, tobacco smoking aggravates the effect of estrogen and endocrine disruptive chemicals from the environment targeting ER may well contribute to the lung carcinogenesis. They have gradually become important issues in the course of preventive medicine.

Pulmonary tuberculosis and lung cancer: simultaneous and sequential occurrence

Directory of Open Access Journals (Sweden)

Denise Rossato Silva

2013-06-01

Full Text Available OBJECTIVE: Lung cancer (LC is the leading cause of cancer-related death and represents a major public health problem worldwide. Another major cause of morbidity and mortality, especially in developing countries, is tuberculosis. The simultaneous or sequential occurrence of pulmonary tuberculosis and LC in the same patient has been reported in various case series and case-control studies. The objective of this study was to describe the characteristics of patients developing tuberculosis and LC, either simultaneously or sequentially. METHODS: This was a cross-sectional study based on the review of medical charts. RESULTS: The study involved 24 patients diagnosed with tuberculosis and LC between 2009 and 2012. The diagnoses of tuberculosis and LC occurred simultaneously in 10 patients, whereas tuberculosis was diagnosed prior to LC in 14. The median time between the two diagnoses was 5 years (interquartile range: 1-30 years. Fourteen patients (58.3% were male, 20 (83.3% were White, and 22 (91.7% were smokers or former smokers. The most common histological type was adenocarcinoma, identified in 14 cases (58.3%, followed by epidermoid carcinoma, identified in 6 (25.0%. Seven patients (29.2% presented with distant metastases at diagnosis; of those 7 patients, 5 (71% were diagnosed with LC and tuberculosis simultaneously. CONCLUSIONS: In the present study, most of the patients with tuberculosis and LC were smokers or former smokers, and tuberculosis was diagnosed either before or simultaneously with LC. Non-small cell lung cancer, especially adenocarcinoma, was the most common histological type.

Radiosensitizing effect of PSMC5, a 19S proteasome ATPase, in H460 lung cancer cells

International Nuclear Information System (INIS)

Yim, Ji-Hye; Yun, Hong Shik; Lee, Su-Jae; Baek, Jeong-Hwa; Lee, Chang-Woo; Song, Ji-Young; Um, Hong-Duck; Park, Jong Kuk; Kim, Jae-Sung; Park, In-Chul; Hwang, Sang-Gu

2016-01-01

The function of PSMC5 (proteasome 26S subunit, ATPase 5) in tumors, particularly with respect to cancer radioresistance, is not known. Here, we identified PSMC5 as a novel radiosensitivity biomarker, demonstrating that radiosensitive H460 cells were converted to a radioresistance phenotype by PSMC5 depletion. Exposure of H460 cells to radiation induced a marked accumulation of cell death-promoting reactive oxygen species, but this effect was blocked in radiation-treated H460 PSMC5-knockdown cells through downregulation of the p53-p21 pathway. Interestingly, PSMC5 depletion in H460 cells enhanced both AKT activation and MDM2 transcription, thereby promoting the degradation of p53 and p21 proteins. Furthermore, specific inhibition of AKT with triciribine or knockdown of MDM2 with small interfering RNA largely restored p21 expression in PSMC5-knockdown H460 cells. Our data suggest that PSMC5 facilitates the damaging effects of radiation in radiation-responsive H460 cancer cells and therefore may serve as a prognostic indicator for radiotherapy and molecular targeted therapy in lung cancer patients. - Highlights: • PSMC5 is a radiation-sensitive biomarker in H460 cells. • PSMC5 depletion inhibits radiation-induced apoptosis in H460 cells. • PSMC5 knockdown blocks ROS generation through inhibition of the p53-p21 pathway. • PSMC5 knockdown enhances p21 degradation via AKT-dependent MDM2 stabilization.

Cytotoxic Effects of Fascaplysin against Small Cell Lung Cancer Cell Lines

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Hamilton, Gerhard

2014-01-01

Fascaplysin, the natural product of a marine sponge, exhibits anticancer activity against a broad range of tumor cells, presumably through interaction with DNA, and/or as a highly selective cyclin-dependent kinase 4 (CDK4) inhibitor. In this study, cytotoxic activity of fascaplysin against a panel of small cell lung cancer (SCLC) cell lines and putative synergism with chemotherapeutics was investigated. SCLC responds to first-line chemotherapy with platinum-based drugs/etoposide, but relapses early with topotecan remaining as the single approved therapeutic agent. Fascaplysin was found to show high cytotoxicity against SCLC cells and to induce cell cycle arrest in G1/0 at lower and S-phase at higher concentrations, respectively. The compound generated reactive oxygen species (ROS) and induced apoptotic cell death in the chemoresistant NCI-H417 SCLC cell line. Furthermore, fascaplysin revealed marked synergism with the topoisomerase I-directed camptothecin and 10-hydroxy-camptothecin. The Poly(ADP-ribose)-Polymerase 1 (PARP1) inhibitor BYK 204165 antagonized the cytotoxic activity of fascaplysin, pointing to the involvement of DNA repair in response to the anticancer activity of the drug. In conclusion, fascaplysin seems to be suitable for treatment of SCLC, based on high cytotoxic activity through multiple routes of action, affecting topoisomerase I, integrity of DNA and generation of ROS. PMID:24608973

Alpinetin inhibits lung cancer progression and elevates sensitization drug-resistant lung cancer cells to cis-diammined dichloridoplatium

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Wu L

2015-11-01

Full Text Available Lin Wu, Wei Yang, Su-ning Zhang, Ji-bin Lu Department of Thoracic Surgery, Sheng Jing Hospital of China Medical University, Shenyang, People’s Republic of China Objective: Alpinetin is a novel flavonoid that has demonstrated potent antitumor activity in previous studies. However, the efficacy and mechanism of alpinetin in treating lung cancer have not been determined. Methods: We evaluated the impact of different doses and durations of alpinetin treatment on the cell proliferation, the apoptosis of lung cancer cells, as well as the drug-resistant lung cancer cells. Results: This study showed that the alpinetin inhibited the cell proliferation, enhanced the apoptosis, and inhibited the PI3K/Akt signaling in lung cancer cells. Moreover, alpinetin significantly increased the sensitivity of drug-resistant lung cancer cells to the chemotherapeutic effect of cis-diammined dichloridoplatium. Taken together, this study demonstrated that alpinetin significantly suppressed the development of human lung cancer possibly by influencing mitochondria and the PI3K/Akt signaling pathway and sensitized drug-resistant lung cancer cells. Conclusion: Alpinetin may be used as a potential compound for combinatorial therapy or as a complement to other chemotherapeutic agents when multiple lines of treatments have failed to reduce lung cancer. Keywords: alpinetin, cell proliferation and apoptosis, drug resistance reversal, PI3K/Akt, lung cancer

NCI-MATCH Trial Links Targeted Drugs to Mutations

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Investigators for the nationwide trial, NCI-MATCH: Molecular Analysis for Therapy Choice, announced that the trial will seek to determine whether targeted therapies for people whose tumors have specific gene mutations will be effective regardless of their cancer type. NCI-MATCH will incorporate more than 20 different study drugs or drug combinations, each targeting a specific gene mutation, in order to match each patient in the trial with a therapy that targets a molecular abnormality in their tumor.

NCI and the Precision Medicine Initiative®

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NCI's activities related to precision medicine focuses on new and expanded precision medicine clinical trials; mechanisms to overcome drug resistance to cancer treatments; and developing a shared digital repository of precision medicine trials data.

Pain management in lung cancer.

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Nurwidya, Fariz; Syahruddin, Elisna; Yunus, Faisal

2016-01-01

Lung cancer is the leading cause of cancer-related mortality worldwide. Not only burdened by the limited overall survival, lung cancer patient also suffer from various symptoms, such as pain, that implicated in the quality of life. Cancer pain is a complicated and transiently dynamic symptom that results from multiple mechanisms. This review will describe the pathophysiology of cancer pain and general approach in managing a patient with lung cancer pain. The use of opioids, nonsteroidal anti-inflammatory drugs (NSAIDs), and adjuvant analgesia, as part of the pharmacology therapy along with interventional strategy, will also be discussed.

Lung Cancer Trends

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... the Biggest Cancer Killer in Both Men and Women” Stay Informed Trends for Other Kinds of Cancer Breast Cervical Colorectal (Colon) Ovarian Prostate Skin Cancer Home Lung Cancer Trends Language: English Español (Spanish) Recommend ...

Curbing the burden of lung cancer.

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Urman, Alexandra; Hosgood, H Dean

2016-06-01

Lung cancer contributes substantially to the global burden of disease and healthcare costs. New screening modalities using low-dose computerized tomography are promising tools for early detection leading to curative surgery. However, the screening and follow-up diagnostic procedures of these techniques may be costly. Focusing on prevention is an important factor to reduce the burden of screening, treatment, and lung cancer deaths. The International Agency for Research on Cancer has identified several lung carcinogens, which we believe can be considered actionable when developing prevention strategies. To curb the societal burden of lung cancer, healthcare resources need to be focused on early detection and screening and on mitigating exposure(s) of a person to known lung carcinogens, such as active tobacco smoking, household air pollution (HAP), and outdoor air pollution. Evidence has also suggested that these known lung carcinogens may be associated with genetic predispositions, supporting the hypothesis that lung cancers attributed to differing exposures may have developed from unique underlying genetic mechanisms attributed to the exposure of interest. For instance, smokingattributed lung cancer involves novel genetic markers of risk compared with HAP-attributed lung cancer. Therefore, genetic risk markers may be used in risk stratification to identify subpopulations that are at a higher risk for developing lung cancer attributed to a given exposure. Such targeted prevention strategies suggest that precision prevention strategies may be possible in the future; however, much work is needed to determine whether these strategies will be viable.

New approaches of PARP-1 inhibitors in human lung cancer cells and cancer stem-like cells by some selected anthraquinone-derived small molecules.

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Yu-Ru Lee

Full Text Available Poly (ADP-ribose polymerase-1 (PARP-1 and telomerase, as well as DNA damage response pathways are targets for anticancer drug development, and specific inhibitors are currently under clinical investigation. The purpose of this work is to evaluate anticancer activities of anthraquinone-derived tricyclic and tetracyclic small molecules and their structure-activity relationships with PARP-1 inhibition in non-small cell lung cancer (NSCLC and NSCLC-overexpressing Oct4 and Nanog clone, which show high-expression of PARP-1 and more resistance to anticancer drug. We applied our library selected compounds to NCI's 60 human cancer cell-lines (NCI-60 in order to generate systematic profiling data. Based on our analysis, it is hypothesized that these drugs might be, directly and indirectly, target components to induce mitochondrial permeability transition and the release of pro-apoptotic factors as potential anti-NSCLC or PARP inhibitor candidates. Altogether, the most active NSC747854 showed its cytotoxicity and dose-dependent PARP inhibitory manner, thus it emerges as a promising structure for anti-cancer therapy with no significant negative influence on normal cells. Our studies present evidence that telomere maintenance should be taken into consideration in efforts not only to overcome drug resistance, but also to optimize the use of telomere-based therapeutics. These findings will be of great value to facilitate structure-based design of selective PARP inhibitors, in general, and telomerase inhibitors, in particular. Together, the data presented here expand our insight into the PARP inhibitors and support the resource-demanding lead optimization of structurally related small molecules for human cancer therapy.

New Approaches of PARP-1 Inhibitors in Human Lung Cancer Cells and Cancer Stem-Like Cells by Some Selected Anthraquinone-Derived Small Molecules

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Yu, Dah-Shyong; Huang, Kuo-Feng; Chou, Shih-Jie; Chen, Tsung-Chih; Lee, Chia-Chung; Chen, Chun-Liang; Chiou, Shih-Hwa; Huang, Hsu-Shan

2013-01-01

Poly (ADP-ribose) polymerase-1 (PARP-1) and telomerase, as well as DNA damage response pathways are targets for anticancer drug development, and specific inhibitors are currently under clinical investigation. The purpose of this work is to evaluate anticancer activities of anthraquinone-derived tricyclic and tetracyclic small molecules and their structure-activity relationships with PARP-1 inhibition in non-small cell lung cancer (NSCLC) and NSCLC-overexpressing Oct4 and Nanog clone, which show high-expression of PARP-1 and more resistance to anticancer drug. We applied our library selected compounds to NCI's 60 human cancer cell-lines (NCI-60) in order to generate systematic profiling data. Based on our analysis, it is hypothesized that these drugs might be, directly and indirectly, target components to induce mitochondrial permeability transition and the release of pro-apoptotic factors as potential anti-NSCLC or PARP inhibitor candidates. Altogether, the most active NSC747854 showed its cytotoxicity and dose-dependent PARP inhibitory manner, thus it emerges as a promising structure for anti-cancer therapy with no significant negative influence on normal cells. Our studies present evidence that telomere maintenance should be taken into consideration in efforts not only to overcome drug resistance, but also to optimize the use of telomere-based therapeutics. These findings will be of great value to facilitate structure-based design of selective PARP inhibitors, in general, and telomerase inhibitors, in particular. Together, the data presented here expand our insight into the PARP inhibitors and support the resource-demanding lead optimization of structurally related small molecules for human cancer therapy. PMID:23451039

Lung cancer mimicking lung abscess formation on CT images

OpenAIRE

Taira, Naohiro; Kawabata, Tsutomu; Gabe, Atsushi; Ichi, Takaharu; Kushi, Kazuaki; Yohena, Tomofumi; Kawasaki, Hidenori; Yamashiro, Toshimitsu; Ishikawa, Kiyoshi

2014-01-01

Patient: Male, 64 Final Diagnosis: Lung pleomorphic carcinoma Symptoms: Cough • fever Medication: — Clinical Procedure: — Specialty: Oncology Objective: Unusual clinical course Background: The diagnosis of lung cancer is often made based on computed tomography (CT) image findings if it cannot be confirmed on pathological examinations, such as bronchoscopy. However, the CT image findings of cancerous lesions are similar to those of abscesses.We herein report a case of lung cancer that resemble...

Inhibition of telomerase activity preferentially targets aldehyde dehydrogenase-positive cancer stem-like cells in lung cancer

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Iniesta Pilar

2011-08-01

Full Text Available Abstract Background Mortality rates for advanced lung cancer have not declined for decades, even with the implementation of novel chemotherapeutic regimens or the use of tyrosine kinase inhibitors. Cancer Stem Cells (CSCs are thought to be responsible for resistance to chemo/radiotherapy. Therefore, targeting CSCs with novel compounds may be an effective approach to reduce lung tumor growth and metastasis. We have isolated and characterized CSCs from non-small cell lung cancer (NSCLC cell lines and measured their telomerase activity, telomere length, and sensitivity to the novel telomerase inhibitor MST312. Results The aldehyde dehydrogenase (ALDH positive lung cancer cell fraction is enriched in markers of stemness and endowed with stem cell properties. ALDH+ CSCs display longer telomeres than the non-CSC population. Interestingly, MST312 has a strong antiproliferative effect on lung CSCs and induces p21, p27 and apoptosis in the whole tumor population. MST312 acts through activation of the ATM/pH2AX DNA damage pathway (short-term effect and through decrease in telomere length (long-term effect. Administration of this telomerase inhibitor (40 mg/kg in the H460 xenograft model results in significant tumor shrinkage (70% reduction, compared to controls. Combination therapy consisting of irradiation (10Gy plus administration of MST312 did not improve the therapeutic efficacy of the telomerase inhibitor alone. Treatment with MST312 reduces significantly the number of ALDH+ CSCs and their telomeric length in vivo. Conclusions We conclude that antitelomeric therapy using MST312 mainly targets lung CSCs and may represent a novel approach for effective treatment of lung cancer.

European position statement on lung cancer screening

DEFF Research Database (Denmark)

Oudkerk, Matthijs; Devaraj, Anand; Vliegenthart, Rozemarijn

2017-01-01

Lung cancer screening with low-dose CT can save lives. This European Union (EU) position statement presents the available evidence and the major issues that need to be addressed to ensure the successful implementation of low-dose CT lung cancer screening in Europe. This statement identified...... specific actions required by the European lung cancer screening community to adopt before the implementation of low-dose CT lung cancer screening. This position statement recommends the following actions: a risk stratification approach should be used for future lung cancer low-dose CT programmes...... need to set a timeline for implementing lung cancer screening....

Can Lung Nodules Be Cancerous?

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... lung nodules be cancerous? Answers from Eric J. Olson, M.D. Yes, lung nodules can be cancerous, ... to determine if it's cancerous. With Eric J. Olson, M.D. AskMayoExpert. Pulmonary nodules. Rochester, Minn.: Mayo ...

NCI Releases Video: Proteogenomics Research - On the Frontier of Precision Medicine | Office of Cancer Clinical Proteomics Research

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The Clinical Proteomic Tumor Analysis Consortium (CPTAC) of the National Cancer Institute (NCI), part of the National Institutes of Health, announces the release of an educational video titled “Proteogenomics Research: On the Frontier of Precision Medicine."  Launched at the HUPO2017 Global Leadership Gala Dinner, catalyzed in part by the Cancer Moonshot initiative and featuring as keynote speaker the 47th Vice President of the United States of America Joseph R.

Photodynamic therapy for multiple primary lung cancer

International Nuclear Information System (INIS)

Konaka, C.; Okunaka, T.; Sakai, H.; Furukawa, K.; Hayata, Y.; Kato, H.

1992-01-01

In recent years, multiple primary lung cancers have been reported with greater frequency. As for the treatment of multiple primary lung cancer, operative excision is usually difficult for all lesions due to problems of pulmonary function. PDT is a good therapeutic modality in the treatment of multiple primary lung cancer, especially central type lung cancer, for preservation of lung function. Since 1980, 50 patients of endoscopically-evaluated early stage lung cancers have been treated with PDT at Tokyo Medical College. Within this group, 16 patients were classified as having multiple primary lung cancers. This paper evaluates the effectiveness of PDT in the treatment of these patients with multiple primary bronchogenic carcinoma. (author). 6 refs., 2 tabs

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

Energy Technology Data Exchange (ETDEWEB)

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

2014-01-24

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

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

International Nuclear Information System (INIS)

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

2014-01-01

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

Design, Synthesis, and Pharmacological Evaluation of Novel Multisubstituted Pyridin-3-amine Derivatives as Multitargeted Protein Kinase Inhibitors for the Treatment of Non-Small Cell Lung Cancer.

Science.gov (United States)

Zhu, Wei; Chen, Hui; Wang, Yulan; Wang, Jiang; Peng, Xia; Chen, Xianjie; Gao, Yinglei; Li, Chunpu; He, Yulong; Ai, Jing; Geng, Meiyu; Zheng, Mingyue; Liu, Hong

2017-07-27

A novel series of pyridin-3-amine derivatives were designed, synthesized, and evaluated as multitargeted protein kinase inhibitors for the treatment of non-small cell lung cancer (NSCLC). Hit 1 was first disclosed by in silico screening against fibroblast growth factor receptors (FGFR), which was subsequently validated by in vitro experiments. The structure-activity relationship (SAR) of its analogues was then explored to afford novel FGFR inhibitors 2a-2p and 3a-3q. Among them, 3m showed potent inhibition against FGFR1, 2, and 3. Interestingly, compound 3m not only inhibited various phosphorylation and downstream signaling across different oncogenic forms in FGFR-overactivated cancer cells but also showed nanomolar level inhibition against several other NSCLC-related oncogene kinases, including RET, EGFR, EGFR/T790M/L858R, DDR2, and ALK. Finally, in vivo pharmacology evaluations of 3m showed significant antitumor activity (TGI = 66.1%) in NCI-H1581 NSCLC xenografts with a good pharmacokinetic profile.

NCI Scientists Awarded National Medal of Technology and Innovation by President Obama | Poster

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Two NCI scientists received the National Medal of Technology and Innovation, the nation’s highest honor for technological achievement. The award was announced by President Obama in October. The honorees, John Schiller, Ph.D., Laboratory of Cellular Oncology (LCO), Center for Cancer Research, NCI, and Douglas Lowy, M.D., also from LCO and NCI deputy director, received their medals at a White House ceremony on Nov. 20.

Customizing Therapies for Lung Cancer | Center for Cancer Research

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Lung cancer is the leading cause of cancer-related death in both men and women. Although there have been modest improvements in short-term survival over the last few decades, five-year survival rates for lung cancer remain low at only 16 percent. Treatment for lung cancer depends on the stage of the disease at diagnosis, but generally consists of some combination of surgery,

HOXA9 inhibits migration of lung cancer cells and its hypermethylation is associated with recurrence in non-small cell lung cancer.

Science.gov (United States)

Hwang, Jung-Ah; Lee, Bo Bin; Kim, Yujin; Hong, Seung-Hyun; Kim, Young-Ho; Han, Joungho; Shim, Young Mog; Yoon, Chae-Yeong; Lee, Yeon-Su; Kim, Duk-Hwan

2015-06-01

This study was aimed at understanding the clinicopathological significance of HOXA9 hypermethylation in non-small cell lung cancer (NSCLC). HOXA9 hypermethylation was characterized in six lung cancer cell lines, and its clinicopathological significance was analyzed using methylation-specific PCR in 271 formalin-fixed paraffin-embedded tissues and 27 fresh-frozen tumor and matched normal tissues from 298 NSCLC patients, and Ki-67 expression was analyzed using immunohistochemistry. The promoter region of HOXA9 was highly methylated in six lung cancer cell lines, but not in normal bronchial epithelial cells. The loss of expression was restored by treatment of the cells with a demethylating agent, 5-aza-2'-deoxycytidine (5-Aza-dC). Transient transfection of HOXA9 into H23 lung cancer cells resulted in the inhibition of cell migration but not proliferation. Conversely, sequence-specific siRNA-mediated knockdown of HOXA9 enhanced cell migration. The mRNA levels of HOXA9 in 27 fresh-frozen tumor tissues were significantly lower than in matched normal tissues (Precurrence-free survival (hazard ratio=3.98, 95% confidence interval = 1.07-17.09, P=0.01) in never-smokers, after adjusting for age, sex, tumor size, adjuvant therapy, pathologic stage, and histology. In conclusion, the present study suggests that HOXA9 inhibits migration of lung cancer cells and its hypermethylation is an independent prognostic factor for recurrence-free survival in never-smokers with NSCLC. © 2014 Wiley Periodicals, Inc.

Profile of lung cancer in kuwait.

Science.gov (United States)

El-Basmy, Amani

2013-01-01

Lung cancer is the most frequent cancer in males and the fourth most frequent site in females, worldwide. This study is the first to explore the profile of lung cancer in Kuwait. Cases of primary lung cancer (Kuwaiti) in Kuwait cancer Registry (KCR) were grouped in 4 periods (10 years each) from 1970-2009. Epidemiological measures; age standardized incidence rate (ASIR) with 95% confidence intervals (CI), Standardized rate ratio (SRR) and Cumulative risk and Forecasting to year 2020-2029 used for analysis. Between years, 2000-2009 lung cancer ranked the 4th and the 9th most frequent cancer in males and females respectively. M:F ratio 1:3. Mean age at diagnosis (95%CI) was 65.2 (63.9-66.4) years. The estimated risk of developing lung cancer before the age of 75 years in males is 1.8% (1/56), and 0.6 (1/167) in females. The ASIR for male cases was 11.7, 17.1, 17.0, 14.0 cases/100,000 population in the seventies, eighties, nineties and in 2000-2009 respectively. Female ASIR was 2.3, 8.4, 5.1, 4.4 cases/100,000 population in the same duration. Lung cancer is the leading cause cancer death in males 168 (14.2%) and the fifth cause of death due to cancer in females accounting for 6.1% of all cancer deaths. The ASMR (95%CI) was 8.1 (6.6-10.0) deaths/100,000 population and 2.8 (1.3-4.3) deaths/100,000 population in males and females respectively. The estimated Mortality to incidence Ratio was 0.6. The incidence of lung cancer between years 2000-2009 is not different from that reported in the seventies. KCR is expecting the number of lung cancer cases to increase.

Intranuclear Delivery of a Novel Antibody-Derived Radiosensitizer Targeting the DNA-Dependent Protein Kinase Catalytic Subunit

Energy Technology Data Exchange (ETDEWEB)

Xiong Hairong [Institute of Molecular Medicine and Genetics, Georgia Health Sciences University, Augusta, GA (Georgia); State Key Laboratory of Virology, Institute of Medical Virology, Wuhan University School of Medicine, Wuhan (China); Lee, Robert J. [Division of Pharmaceutics, College of Pharmacy, Ohio State University, Columbus, OH (United States); Haura, Eric B. [Thoracic Oncology and Experimental Therapeutics Programs, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (United States); Edwards, John G. [Apeliotus Technologies, Inc., Atlanta, GA (United States); Dynan, William S. [Institute of Molecular Medicine and Genetics, Georgia Health Sciences University, Augusta, GA (Georgia); Li Shuyi, E-mail: sli@georgiahealth.edu [Institute of Molecular Medicine and Genetics, Georgia Health Sciences University, Augusta, GA (Georgia); Apeliotus Technologies, Inc., Atlanta, GA (United States)

2012-07-01

Purpose: To inhibit DNA double-strand break repair in tumor cells by delivery of a single-chain antibody variable region fragment (ScFv 18-2) to the cell nucleus. ScFv 18-2 binds to a regulatory region of the DNA-dependent protein kinase (DNA-PK), an essential enzyme in the nonhomologous end-joining pathway, and inhibits DNA end-joining in a cell-free system and when microinjected into single cells. Development as a radiosensitizer has been limited by the lack of a method for intranuclear delivery to target cells. We investigated a delivery method based on folate receptor-mediated endocytosis. Methods and Materials: A recombinant ScFv 18-2 derivative was conjugated to folate via a scissile disulfide linker. Folate-ScFv 18-2 was characterized for its ability to be internalized by tumor cells and to influence the behavior of ionizing radiation-induced repair foci. Radiosensitization was measured in a clonogenic survival assay. Survival curves were fitted to a linear-quadratic model, and between-group differences were evaluated by an F test. Sensitization ratios were determined based on mean inhibitory dose. Results: Human KB and NCI-H292 lung cancer cells treated with folate-conjugated ScFv 18-2 showed significant radiosensitization (p < 0.001). Sensitization enhancement ratios were 1.92 {+-} 0.42 for KB cells and 1.63 {+-} 0.13 for NCI-H292 cells. Studies suggest that treatment inhibits repair of radiation-induced DSBs, as evidenced by the persistence of {gamma}-H2AX-stained foci and by inhibition of staining with anti-DNA-PKcs phosphoserine 2056. Conclusions: Folate-mediated endocytosis is an effective method for intranuclear delivery of an antibody-derived DNA repair inhibitor.

Radioimmunoscintigraphy in lung cancer diagnosing

International Nuclear Information System (INIS)

Hadjikostova, H.

1999-01-01

As the lung cancer is the leading cause of death from cancer at males, the exact staging is essential. Monoclonal antibodies marked with radionuclides like 131 I, 111 In, 99m Tc, etc., allow detecting and staging the small cell lung cancer with sensibility 90%, specificity 45% and accuracy 85%. It is suggested this method to be applied simultaneously with computerized tomography. The diagnostic possibility of radioimmunoscintigraphy (RIS) in earlier detection, recurrence or metastasis as well as follow up the effect of therapy performed at patients with lung cancer are reviewed. RIS is performed with IODOMAB-R-2 (Sorin Biomedica) 131 I antiCEA Mob F(ab') 2 , dose 92.5-185 MBq. Planar images were performed 72 hours after i.v. injection. Four patients with epidermoid squamous cell cancer were examined. Positive results were obtained at 3 patients and one false negative. In general sensitivity of radioimmunoscintigraphy of lung cancer is 75-90%. However there are difficulties at its application linked with necessity of permanent availability of radiolabelled antibodies with high specific activity at the moment of their injection. Despite all radioimmunoscintigraphy is developing as an useful diagnostic method for evaluation and follow up of lung cancer patients

Optical and Functional Imaging in Lung Cancer

NARCIS (Netherlands)

K.H. van der Leest (Cor)

2010-01-01

textabstractLung cancer is the second most common cancer in men and women, and is the leading cause of cancer related death. In industrialized countries the mortality rate of lung cancer is higher than the mortality rate of breast, colorectal and prostate cancer combined 1. When lung cancer is

Lung cancer screening: Update

International Nuclear Information System (INIS)

Kim, Hyea Young

2015-01-01

Lung cancer is the leading cause of cancer deaths worldwide as well as in Korea. A recent National Lung Screening Trial in U.S. revealed that low-dose CT (LDCT) screening reduced lung cancer specific mortality by 20% in high risk individuals as compared to chest radiograph screening. Based on this evidence, several expert societies in U.S. and Korean multisociety collaborative committee developed guidelines for recommendation of lung cancer screening using annual LDCT in high risk populations. In most of the societies high risk groups are defined as persons aged 55 to 74 years, who are current smokers with history of smoking of more than 30 packs per year or ex-smokers, who quit smoking up to 15 or more years ago. The benefits of LDCT screening are modestly higher than the harms in high risk individuals. The harms included a high rate of false-positive findings, over-diagnosis and radiation-related deaths. Invasive diagnostic procedure due to false positive findings may lead to complications. LDCT should be performed in qualified hospitals and interpreted by expert radiologists. Recently, the American College of Radiology released the current version of Lung cancer CT screening Reporting and Data Systems. Education and actions to stop smoking must be offered to current smokers

Lung cancer screening: Update

Energy Technology Data Exchange (ETDEWEB)

Kim, Hyea Young [Dept. of Radiology, Center for Lung Cancer, National Cancer Center, Goyang (Korea, Republic of)

2015-09-15

Lung cancer is the leading cause of cancer deaths worldwide as well as in Korea. A recent National Lung Screening Trial in U.S. revealed that low-dose CT (LDCT) screening reduced lung cancer specific mortality by 20% in high risk individuals as compared to chest radiograph screening. Based on this evidence, several expert societies in U.S. and Korean multisociety collaborative committee developed guidelines for recommendation of lung cancer screening using annual LDCT in high risk populations. In most of the societies high risk groups are defined as persons aged 55 to 74 years, who are current smokers with history of smoking of more than 30 packs per year or ex-smokers, who quit smoking up to 15 or more years ago. The benefits of LDCT screening are modestly higher than the harms in high risk individuals. The harms included a high rate of false-positive findings, over-diagnosis and radiation-related deaths. Invasive diagnostic procedure due to false positive findings may lead to complications. LDCT should be performed in qualified hospitals and interpreted by expert radiologists. Recently, the American College of Radiology released the current version of Lung cancer CT screening Reporting and Data Systems. Education and actions to stop smoking must be offered to current smokers.

Bidi smoking and lung cancer.

Science.gov (United States)

Prasad, Rajendra; Singhal, Sanjay; Garg, Rajiv

2009-04-01

This article discusses the role of bidi smoking as a risk factor for lung cancer. A review of the documented evidence is presented. The literature from Pubmed has been searched using the key words 'beedi smoking', 'bidi smoking' and 'lung cancer'. The bibliographies of all papers found were further searched for additional relevant articles. After this thorough search, eight studies were found. The evidence suggests that bidi smoking poses a higher risk for lung cancer than cigarette smoking and risk further increases with both the length of time and amount of bidi smoking. The focus of tobacco control programs should be expanded to all types of tobacco use, including bidis, to reduce the increasing problem of lung cancer.

Current questions in HIV-associated lung cancer.

Science.gov (United States)

Shcherba, Marina; Shuter, Jonathan; Haigentz, Missak

2013-09-01

In this review, we explore current questions regarding risk factors contributing to frequent and early onset of lung cancer among populations with HIV infection, treatment, and outcomes of lung cancer in HIV-infected patients as well as challenges in a newly evolving era of lung cancer screening. Lung cancer, seen in three-fold excess in HIV-infected populations, has become the most common non-AIDS defining malignancy in the highly active antiretroviral therapy era. HIV-associated lung cancer appears to be associated with young age at diagnosis, cigarette smoking, advanced stage at presentation, and a more aggressive clinical course. There is no unified explanation for these observations, and aside from traditional risk factors, HIV-related immunosuppression and biological differences might play a role. In addition to smoking cessation interventions, screening and early cancer detection in HIV-infected populations are of high clinical importance, although evidence supporting lung cancer screening in this particularly high-risk subset is currently lacking, as are prospective studies of lung cancer therapy. There is an urgent need for prospective clinical trials in HIV-associated lung cancer to improve understanding of lung cancer pathogenesis and to optimize patient care. Several clinical trials are in progress to address questions in cancer biology, screening, and treatment for this significant cause of mortality in persons with HIV infection.

What You Need to Know about Lung Cancer

Science.gov (United States)

... Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin Cancer ... Publications Reports What You Need To Know About™ Lung Cancer This booklet is about lung cancer. Learning about ...

Impact of Toxicity Grade and Scoring System on the Relationship Between Mean Lung Dose and Risk of Radiation Pneumonitis in a Large Cohort of Patients With Non-Small Cell Lung Cancer

International Nuclear Information System (INIS)

Tucker, Susan L.; Jin Hekun; Wei Xiong

2010-01-01

Purpose: To compute the risk of radiation pneumonitis (RP) as a function of mean lung dose (MLD), with RP scored using three grading systems and analyzed at four threshold levels of toxicity in a large cohort of patients with non-small cell lung cancer (NSCLC) treated with definitive radiotherapy (RT). Methods and Materials: On the basis of medical records and radiographic images, RP was scored retrospectively in 442 patients with NSCLC who had ≥6 months of follow-up after the end of RT. The severity of RP was scored for each patient using the National Cancer Institute (NCI) Common Toxicity Criteria, version 2.0 (CTC2.0); the NCI Common Terminology Criteria for Adverse Events, version 3.0 (CTCAE3.0); and the grading system of the Radiation Therapy Oncology Group (RTOG). For each grading system and for each of four levels of toxicity (Grade ≥1, ≥2, ≥3, ≥4), the Lyman, logistic, and log-logistic normal tissue complication probability (NTCP) models were fitted to the data as functions of MLD. The parameter estimates from the model fits are listed in table form, and the RP risk estimates are presented graphically for the Lyman and log-logistic NTCP models. Results: The results presented here illustrate the impact of scoring system and level of toxicity on the relationship between MLD and RP risk. Conclusions: These results facilitate quantitative comparisons between our data and studies of RP risk reported by others, and several examples of such comparisons are provided.

Human Monoclonal Antibodies Targeting Glypican-2 in Neuroblastoma | NCI Technology Transfer Center | TTC

Science.gov (United States)

Researchers at the National Cancer Institute’s Laboratory of Molecular Biology (NCI LMB) have developed and isolated several single domain monoclonal human antibodies against GPC2. NCI seeks parties interested in licensing or co-developing GPC2 antibodies and/or conjugates.

Arctigenin enhances chemosensitivity to cisplatin in human nonsmall lung cancer H460 cells through downregulation of survivin expression.

Science.gov (United States)

Wang, Huan-qin; Jin, Jian-jun; Wang, Jing

2014-01-01

Arctigenin, a dibenzylbutyrolactone lignan, enhances cisplatin-mediated cell apoptosis in cancer cells. Here, we sought to investigate the effects of arctigenin on cisplatin-treated non-small-cell lung cancer (NSCLC) H460 cells. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and annexin-V/propidium iodide staining were performed to analyze the proliferation and apoptosis of H460 cells. Arctigenin dose-dependently suppressed cell proliferation and potentiated cell apoptosis, coupled with increased cleavage of caspase-3 and poly(ADP-ribose) polymerase. Moreover, arctigenin sensitized H460 cells to cisplatin-induced proliferation inhibition and apoptosis. Arctigenin alone or in combination with cisplatin had a significantly lower amount of survivin. Ectopic expression of survivin decreased cell apoptosis induced by arctigenin (P arctigenin (P arctigenin has a therapeutic potential in combina-tion with chemotherapeutic agents for NSLC. © 2013 Wiley Periodicals, Inc.

Pathological review of lung cancer among A-bomb survivors at Hiroshima Atomic-bomb Hospital

International Nuclear Information System (INIS)

Nambu, Shigeru; Akamizu, Hiroshi; Kuramoto, Kiyoshi; Hamada, Tadao.

1989-01-01

Autopsy findings were reviewed in 161 A-bomb survivors with lung cancer during the period 1956-1987. The overall ratio of male to female was 2.1. In the group of A-bomb survivors exposed at ≤2,000 m from the hypocenter, the ratio of male to female in the incidence of lung cancer was 1.3. According to age groups, it was the highest in people in their seventies. Histology revealed that the incidence was 41.6% for adenocarcinoma, 29.2% for squamous cell carcinoma, 19.9% for small cell carcinoma, 6.8% for large cell carcinoma, and 2.5% for adenosquamous cell carcinoma. The incidence of small cell carcinoma was relatively high in the ≤2,000 m group. For females in the ≤2,000 m group, the incidence of adenocarcinoma was relatively low, and the incidences of squamous cell carcinoma and small cell carcinoma tended to be high. The incidence of histologic type of lung cancer varied with time: squamous cell carcinoma and small cell carcinoma were the most predominant during the period 1957-1967; since 1968, it has been gradually replacing by adenocarcinoma. In the ≤2,000 m group, however, small cell carcinoma has still been more predominant even since 1984. For 8 A-bomb survivors exposed at the age of 20 years or less, 7 had adenocarcinoma, showing a significantly higher incidence than those exposed at older ages. (Namekawa, K)

Expression and promoter DNA methylation of MLH1 in colorectal cancer and lung cancer.

Science.gov (United States)

Ma, Yunxia; Chen, Yuan; Petersen, Iver

2017-04-01

Aberrant DNA methylation is a common molecular feature in human cancer. The aims of this study were to analyze the methylation status of MLH1, one of the DNA mismatch repair (MMR) genes, in human colorectal and lung cancer and to evaluate its clinical relevance. The expression of MLH1 was analyzed in 8 colorectal cancer (CRC) and 8 lung cancer cell lines by real-time RT-PCR and western blotting. The MLH1 protein expression was evaluated by immunohistochemistry on tissue microarrays including 121 primary CRC and 90 lung cancer patient samples. In cancer cell lines, the methylation status of MLH1 promoter and exon 2 was investigated by bisulfite sequencing (BS). Methylation-specific-PCR (MSP) was used to evaluate methylation status of MLH1. The expression of MLH1 mRNA was detected in 8 CRC cell lines as well as normal colonic fibroblast cells CCD-33Co. At protein levels, MLH1 was lost in one CRC cell line HCT-116 and normal cells CCD-33Co. No methylation was found in the promoter and exon 2 of MLH1 in CRC cell lines. MLH1 was expressed in 8 lung cancer cell lines at both mRNA and protein levels. Compared to cancer cells, normal bronchial epithelial cells (HBEC) had lower expression of MLH1 protein. In primary CRC, 54.5% of cases exhibited positive staining, while 47.8% of lung tumors were positive for MLH1 protein. MSP analysis showed that 58 out of 92 (63.0%) CRC and 41 out of 73 (56.2%) lung cancer exhibited MLH1 methylation. In CRC, the MLH1 methylation was significantly associated with tumor invasion in veins (P=0.012). However, no significant links were found between MLH1 expression and promoter methylation in both tumor entities. MLH1 methylation is a frequent molecular event in CRC and lung cancer patients. In CRC, methylation of MLH1 could be linked to vascular invasiveness. Copyright © 2017 Elsevier GmbH. All rights reserved.

Improving clinical research and cancer care delivery in community settings: evaluating the NCI community cancer centers program

Directory of Open Access Journals (Sweden)

Fennell Mary L

2009-09-01

Full Text Available Abstract Background In this article, we describe the National Cancer Institute (NCI Community Cancer Centers Program (NCCCP pilot and the evaluation designed to assess its role, function, and relevance to the NCI's research mission. In doing so, we describe the evolution of and rationale for the NCCCP concept, participating sites' characteristics, its multi-faceted aims to enhance clinical research and quality of care in community settings, and the role of strategic partnerships, both within and outside of the NCCCP network, in achieving program objectives. Discussion The evaluation of the NCCCP is conceptualized as a mixed method multi-layered assessment of organizational innovation and performance which includes mapping the evolution of site development as a means of understanding the inter- and intra-organizational change in the pilot, and the application of specific evaluation metrics for assessing the implementation, operations, and performance of the NCCCP pilot. The assessment of the cost of the pilot as an additional means of informing the longer-term feasibility and sustainability of the program is also discussed. Summary The NCCCP is a major systems-level set of organizational innovations to enhance clinical research and care delivery in diverse communities across the United States. Assessment of the extent to which the program achieves its aims will depend on a full understanding of how individual, organizational, and environmental factors align (or fail to align to achieve these improvements, and at what cost.

Small Molecular TRAIL Inducer ONC201 Induces Death in Lung Cancer Cells: A Preclinical Study

OpenAIRE

Feng, Yuan; Zhou, Jihong; Li, Zhanhua; Jiang, Ying; Zhou, Ying

2016-01-01

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) selectively targets cancer cells. The present preclinical study investigated the anti-cancer efficiency of ONC201, a first-in-class small molecule TRAIL inducer, in lung cancer cells. We showed that ONC201 was cytotoxic and anti-proliferative in both established (A549 and H460 lines) and primary human lung cancer cells. It was yet non-cytotoxic to normal lung epithelial cells. Further, ONC201 induced exogenous apoptosis act...

Epidemiology, aetiology, diagnosis and screening of lung cancer

International Nuclear Information System (INIS)

Berzinec, P.

2006-01-01

Lung cancer is the leading cause of cancer death globally. Smoking causes about 90 % of all lung cancer cases. Passive, i.e. involuntary smoking has been confirmed to enhance the risk of lung cancer in exposed people. Individual susceptibility is one of important factors in lung cancer formation. New knowledge in epidemiology and aetiology of lung cancer gives new possibilities in diagnostic and screening of this disease. Results of large randomised trials aimed at new technologies in lung cancer screening will be available in a few years. (author)

The distribution of a new /sup 111/In-Bleomycin complex in tumor cells by autoradiography

International Nuclear Information System (INIS)

Hou, D.Y.; Maruyama, Y.

1987-01-01

A new radioactive form of Bleomycin (/sup 111/In-BLMC) was effective for tumor imaging and therapy in mouse glioma and human small cell lung cancer (SCLC) cells. The distribution of drug in tumor cells was investigated by autoradiography. Human small cell lung cancer (N417 and H526, NCI) were exposed to /sup 111/ InCl/sub 3/ and (25-150 μCi/ml) or /sup 111/In-BLMC (25-150 μCi) carried by 15-25 μg BLM/ml) in 37 0 C for 1 hr, 3 hr or 24 hr, washed with fresh medium, and spread. The slides were smeared with NTB/sub 2/ or NTB/sub 3/ emulsion by using wet-mounting or dry-mounting technique and developed 3-14 days. The /sup 111/In-BLMC localized on the cell nucleus (47.8%) and nuclear membrane (29.2%); /sup 111/InCl/sub 3/ located mainly in the cytoplasm (45.8%). This indicates that the mechanism of killing of tumor cells may be related to the drug uptake and distribution of /sup 111/In-BLMC. A nuclear and nuclear membrane localization would favor damage to chromosomes and DNA

Creating Start-up Companies around NCI Inventions | Poster

Science.gov (United States)

By Karen Surabian, Thomas Stackhouse, and Rose Freel, Contributing Writers, and Rosemarie Truman, Guest Writer The National Cancer Institute (NCI), led by the Technology Transfer Center (TTC),  the Avon Foundation, and The Center for Advancing Innovation have partnered to create a “first-of-a-kind” Breast Cancer Start-up Challenge.

DZNep, inhibitor of S-adenosylhomocysteine hydrolase, down-regulates expression of SETDB1 H3K9me3 HMTase in human lung cancer cells.

Science.gov (United States)

Lee, Ju-Kyung; Kim, Keun-Cheol

2013-09-06

3-Deazaneplanocin A (DZNep), an epigenetic anticancer drug, leads to the indirect suppression of S-adenosyl methionine-dependent cellular methylations by inhibiting S-adenosyl homocystein (AdoHcy) hydrolase. Although it is well known that DZNep targets the degradation of EZH2 protein, H3K27me3 HMTase, there are still uncertainties about the regulation of other types of HMTases during cell death. In this study, we describe that SETDB1 gene expression was regulated by DZNep treatment in human lung cancer cells. We confirm that DZNep induced growth inhibition and increased the dead cell population of lung cancer cells. DZNep treatment affected histone methylations, including H3K27me3 and H3K9me3, but not H3K4me3. Reduced levels of H3K27me3 and H3K9me3 were related with the decreased EZH2 and SETDB1 proteins. Real time PCR analysis showed that SETDB1 gene expression was decreased by DZNep treatment, but no effect was observed for EZH2 gene expression. We cloned the promoter region of SETDB1 and SUV39H1 genes, and performed luciferase assays. The promoter activity of SETDB1 gene was down regulated by DZNep treatment, whereas no effect on SUV39H1 promoter activity was observed. In conclusion, we suggest that DZNep regulates not only on H3K27me3 HMTase EZH2, but also H3K9 HMTase SETDB1 gene expression at the transcription level, implicating that the mechanism of action of DZNep targets multiple HMTases during the death of lung cancer cells. Copyright © 2013 Elsevier Inc. All rights reserved.

NCI investment in nanotechnology: achievements and challenges for the future.

Science.gov (United States)

Dickherber, Anthony; Morris, Stephanie A; Grodzinski, Piotr

2015-01-01

Nanotechnology offers an exceptional and unique opportunity for developing a new generation of tools addressing persistent challenges to progress in cancer research and clinical care. The National Cancer Institute (NCI) recognizes this potential, which is why it invests roughly $150 M per year in nanobiotechnology training, research and development. By exploiting the various capacities of nanomaterials, the range of nanoscale vectors and probes potentially available suggests much is possible for precisely investigating, manipulating, and targeting the mechanisms of cancer across the full spectrum of research and clinical care. NCI has played a key role among federal R&D agencies in recognizing early the value of nanobiotechnology in medicine and committing to its development as well as providing training support for new investigators in the field. These investments have allowed many in the research community to pursue breakthrough capabilities that have already yielded broad benefits. Presented here is an overview of how NCI has made these investments with some consideration of how it will continue to work with this research community to pursue paradigm-changing innovations that offer relief from the burdens of cancer. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

Screening for lung cancer

DEFF Research Database (Denmark)

Infante, Maurizio V; Pedersen, Jesper H

2010-01-01

In lung cancer screening with low-dose spiral computed tomography (LDCT), the proportion of stage I disease is 50-85%, and the survival rate for resected stage I disease can exceed 90%, but proof of real benefit in terms of lung cancer mortality reduction must come from the several randomized...

Comparison of quick recovery outcome of inhalable doxorubicin and cisplatin in lung cancer patients: a randomized, double-blind, single-center trial.

Science.gov (United States)

Li, Zhen; Song, Min; He, Zhun; Zong, Ling; Jiang, Bo; Zhang, Tao; Hu, Zhiliang

2018-05-01

Systematic chemotherapy has required high time span for recovery in cancer patients, serious toxic effects, and increased the time of cancer-free survival of patient but decreased the overall survival time of patients irrespective of diseased condition(s). To compare the quick recovery of inhalable doxorubicin and cisplatin in the lung cancer patients. A total of 240 patients with non-small cell lung cancer (NSCLC) patients were randomly divided into two groups of 120 each. Patients had inhaled 25 mg/m 2 doxorubicin (DON group) or 10 mg/m 2 cisplatin (CPN group) once in a day for 21 days. Volume, diameter, type, and a number of lung nodes, pulmonary function, and 21-day lung cancer risk assessment were evaluated. One-way ANOVA following Bonferroni multiple comparison tests was performed at 95% of confidence level. DON and CPN both groups had shrunken the lung cancer nodule, decreased solid nodules and non-solid nodules, and increased partially solid nodules. The DON group (5.88 ± 3.98%) had strongly decreased nodule size than the CPN group (4.15 ± 2.92%; p < 0.0001, q = 3.721). The incidence of nodular size reduction was 9.47 ± 1.13% higher for doxorubicin than cisplatin. The CPN group had 36.53 ± 0.66% and the DON group had 34.65 ± 0.7% lung cancer risk assessment after 21 days (p < 0.0001, q = 3.785). Inhalable doxorubicin might be an effective therapy in NSCLC patients with acceptable hematologic and non-hematologic toxic effects. researchregistry3382, dated 28 December 2014 ( www.researchregistry.com ).

Multi-Modal Imaging in a Mouse Model of Orthotopic Lung Cancer.

Science.gov (United States)

Patel, Priya; Kato, Tatsuya; Ujiie, Hideki; Wada, Hironobu; Lee, Daiyoon; Hu, Hsin-Pei; Hirohashi, Kentaro; Ahn, Jin Young; Zheng, Jinzi; Yasufuku, Kazuhiro

2016-01-01

Investigation of CF800, a novel PEGylated nano-liposomal imaging agent containing indocyanine green (ICG) and iohexol, for real-time near infrared (NIR) fluorescence and computed tomography (CT) image-guided surgery in an orthotopic lung cancer model in nude mice. CF800 was intravenously administered into 13 mice bearing the H460 orthotopic human lung cancer. At 48 h post-injection (peak imaging agent accumulation time point), ex vivo NIR and CT imaging was performed. A clinical NIR imaging system (SPY®, Novadaq) was used to measure fluorescence intensity of tumor and lung. Tumor-to-background-ratios (TBR) were calculated in inflated and deflated states. The mean Hounsfield unit (HU) of lung tumor was quantified using the CT data set and a semi-automated threshold-based method. Histological evaluation using H&E, the macrophage marker F4/80 and the endothelial cell marker CD31, was performed, and compared to the liposomal fluorescence signal obtained from adjacent tissue sections. The fluorescence TBR measured when the lung is in the inflated state (2.0 ± 0.58) was significantly greater than in the deflated state (1.42 ± 0.380 (n = 7, p<0.003). Mean fluorescent signal in tumor was highly variable across samples, (49.0 ± 18.8 AU). CT image analysis revealed greater contrast enhancement in lung tumors (a mean increase of 110 ± 57 HU) when CF800 is administered compared to the no contrast enhanced tumors (p = 0.0002). Preliminary data suggests that the high fluorescence TBR and CT tumor contrast enhancement provided by CF800 may have clinical utility in localization of lung cancer during CT and NIR image-guided surgery.

Bricklayers and lung cancer risk

NARCIS (Netherlands)

Cremers, Jan

2014-01-01

The article ‘Lung cancer risk among bricklayers in a pooled analysis of case–control studies’ in the International Journal of Cancer publishes findings of an epidemiological study (in the frame of a SYNERGY-project) dedicated to the lung cancer risk among bricklayers. The authors conclude that a

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

DEFF Research Database (Denmark)

Stahel, R; Thatcher, N; Früh, M

2011-01-01

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

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

DEFF Research Database (Denmark)

Stahel, R; Thatcher, N; Früh, M

2011-01-01

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

Interest in internet lung cancer support among rural cardiothoracic patients.

Science.gov (United States)

Quin, Jacquelyn; Stams, Victor; Phelps, Beth; Boley, Theresa; Hazelrigg, Stephen

2010-05-01

The Internet may provide an alternative option for rural lung cancer patients who lack access to on-site cancer support; however, Internet access and use among rural patients is unknown. An anonymous waiting-room survey was administered to all outpatient cardiothoracic surgery patients over 3 mo. Survey questions included age, gender, and diagnosis, possession of a home computer and Internet service, estimated Internet use, and use of the Internet for health information. Patients with known or suspected lung cancer were asked to indicate their interest in on-site and Internet cancer support. There were 597 returned surveys (response rate 96%). The mean age was 64.6 y (SE 0.55), and 58% were men. Diagnoses included known or possible lung cancer (15.4%), lung disease (9.5%), heart disease (30.4%), other diagnoses (13.9%), and undetermined (30.6%). There were 343 patients (57.4%) with a home computer and 299 (50.1%) with home Internet service. Average Internet use was 8.5 h per wk (n = 298), and 225 patients used the Internet for health information. Of the 92 patients with lung cancer, 10 indicated interest in on-site support services while 37 expressed interest in Internet-based support. Based on survey results, a slight majority of rural patients have a home computer and Internet access. Internet use for health information appears relatively common. Overall interest for support services among lung cancer patients appears modest with a greater interest in Internet-based services compared with on-site support. Copyright 2010 Elsevier Inc. All rights reserved.

Review of radon and lung cancer risk

International Nuclear Information System (INIS)

Samet, J.M.; Hornung, R.W.

1990-01-01

Radon, a long-established cause of lung cancer in uranium and other underground miners, has recently emerged as a potentially important cause of lung cancer in the general population. The evidence for widespread exposure of the population to radon and the well-documented excess of lung cancer among underground miners exposed to radon decay products have raised concern that exposure to radon progeny might also be a cause of lung cancer in the general population. To date, epidemiological data on the lung cancer risk associated with environmental exposure to radon have been limited. Consequently, the lung cancer hazard posed by radon exposure in indoor air has been addressed primarily through risk estimation procedures. The quantitative risks of lung cancer have been estimated using exposure-response relations derived from the epidemiological investigations of uranium and other underground miners. We review five of the more informative studies of miners and recent risk projection models for excess lung cancer associated with radon. The principal models differ substantially in their underlying assumptions and consequently in the resulting risk projections. The resulting diversity illustrates the substantial uncertainty that remains concerning the most appropriate model of the temporal pattern of radon-related lung cancer. Animal experiments, further follow-up of the miner cohorts, and well-designed epidemiological studies of indoor exposure should reduce this uncertainty. 18 references

Isolated lung events following radiation for early stage breast cancer: incidence and predictors for primary lung vs metastatic breast cancer

International Nuclear Information System (INIS)

Van Buren, Teresa A; Harris, Jay R; Sugarbaker, David J; Schneider, Lindsey; Healey, Elizabeth A

1995-01-01

Purpose: 1) To define the incidence of isolated lung events in a cohort of women treated with conservative surgery (CS) and radiation therapy (RT) for early stage breast cancer. 2) Among such patients, to define the relative distribution of primary lung cancer, metastatic breast cancer, and indeterminate lesions; and to identify any predictors for a diagnosis of lung vs metastatic breast cancer. 3) To examine the cohort with respect to whether a higher than expected incidence of lung cancer is seen following breast irradiation. Materials and Methods: Between 1968 and 1986, 1865 patients with clinical stage I-II breast cancer were treated with CS and RT; the median follow-up for surviving patients is 129 months. The study population was limited to patients who developed a subsequent isolated lung event as the first site of distant disease. Isolated lung event was defined as disease limited to the thoracic cavity, without evidence of either uncontrolled local breast disease or metastatic disease elsewhere. Diagnosis of the lung event as a primary lung cancer, a metastatic breast lesion, or an indeterminate lesion was documented from the viewpoint of 1) the pathologic analysis and 2) the clinical impression at the time of the lung event. Results: Sixty six of the 1865 patients (3.5%) developed an isolated lung event. The relative distribution of the pathologic and clinical diagnoses is shown below: The 66 lung events were characterized either as a solitary pulmonary nodule (27), multiple nodules (23), pleural effusion alone (10), unknown (2), or miscellaneous other findings (4). Among the 47 patients for whom pathology was available, the diagnosis remained indeterminate for 24 (51%). For patients with a definitive pathologic diagnosis, 69% ((9(13))) of smokers had a new lung cancer compared to 20% ((2(10))) of non-smokers (p=0.036), and 67% ((10(15))) of patients with a solitary pulmonary nodule had lung cancer compared to 14% ((1(7))) for other lung presentations (p

Risks of Lung Cancer Screening

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... in women. Different factors increase or decrease the risk of lung cancer. Anything that increases your chance ... been studied to see if they decrease the risk of dying from lung cancer. The following screening ...

Maternal lung cancer and testicular cancer risk in the offspring.

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Kaijser, Magnus; Akre, Olof; Cnattingius, Sven; Ekbom, Anders

2003-07-01

It has been hypothesized that smoking during pregnancy could increase the offspring's risk for testicular cancer. This hypothesis is indirectly supported by both ecological studies and studies of cancer aggregations within families. However, results from analytical epidemiological studies are not consistent, possibly due to methodological difficulties. To further study the association between smoking during pregnancy and testicular cancer, we did a population-based cohort study on cancer risk among offspring of women diagnosed with lung cancer. Through the use of the Swedish Cancer Register and the Swedish Second-Generation Register, we identified 8,430 women who developed lung cancer between 1958 and 1997 and delivered sons between 1941 and 1979. Cancer cases among the male offspring were then identified through the Swedish Cancer Register. Standardized incidence ratios were computed, using 95% confidence intervals. We identified 12,592 male offspring of mothers with a subsequent diagnosis of lung cancer, and there were 40 cases of testicular cancer (standardized incidence ratio, 1.90; 95% confidence interval, 1.35-2.58). The association was independent of maternal lung cancer subtype, and the risk of testicular cancer increased stepwise with decreasing time interval between birth and maternal lung cancer diagnosis. Our results support the hypothesis that exposure to cigarette smoking in utero increases the risk of testicular cancer.

Global Proteome Analysis of the NCI-60 Cell Line Panel

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Amin Moghaddas Gholami

2013-08-01

Full Text Available The NCI-60 cell line collection is a very widely used panel for the study of cellular mechanisms of cancer in general and in vitro drug action in particular. It is a model system for the tissue types and genetic diversity of human cancers and has been extensively molecularly characterized. Here, we present a quantitative proteome and kinome profile of the NCI-60 panel covering, in total, 10,350 proteins (including 375 protein kinases and including a core cancer proteome of 5,578 proteins that were consistently quantified across all tissue types. Bioinformatic analysis revealed strong cell line clusters according to tissue type and disclosed hundreds of differentially regulated proteins representing potential biomarkers for numerous tumor properties. Integration with public transcriptome data showed considerable similarity between mRNA and protein expression. Modeling of proteome and drug-response profiles for 108 FDA-approved drugs identified known and potential protein markers for drug sensitivity and resistance. To enable community access to this unique resource, we incorporated it into a public database for comparative and integrative analysis (http://wzw.tum.de/proteomics/nci60.

NCI Helps Children’s Hospital of Philadelphia to Identify and Treat New Target in Pediatric Cancer | Poster

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There may be a new, more effective method for treating high-risk neuroblastoma, according to scientists at the Children’s Hospital of Philadelphia and collaborators in the Cancer and Inflammation Program at NCI at Frederick. Together, the groups published a study describing a previously unrecognized protein on neuroblastoma cells, called GPC2, as well as the creation of a

Pharmacologically directed strategies in academic anticancer drug discovery based on the European NCI compounds initiative.

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Hendriks, Hans R; Govaerts, Anne-Sophie; Fichtner, Iduna; Burtles, Sally; Westwell, Andrew D; Peters, Godefridus J

2017-07-11

The European NCI compounds programme, a joint initiative of the EORTC Research Branch, Cancer Research Campaign and the US National Cancer Institute, was initiated in 1993. The objective was to help the NCI in reducing the backlog of in vivo testing of potential anticancer compounds, synthesised in Europe that emerged from the NCI in vitro 60-cell screen. Over a period of more than twenty years the EORTC-Cancer Research Campaign panel reviewed ∼2000 compounds of which 95 were selected for further evaluation. Selected compounds were stepwise developed with clear go/no go decision points using a pharmacologically directed programme. This approach eliminated quickly compounds with unsuitable pharmacological properties. A few compounds went into Phase I clinical evaluation. The lessons learned and many of the principles outlined in the paper can easily be applied to current and future drug discovery and development programmes. Changes in the review panel, restrictions regarding numbers and types of compounds tested in the NCI in vitro screen and the appearance of targeted agents led to the discontinuation of the European NCI programme in 2017 and its transformation into an academic platform of excellence for anticancer drug discovery and development within the EORTC-PAMM group. This group remains open for advice and collaboration with interested parties in the field of cancer pharmacology.

Lung cancer after internal alpha-exposure of the lung from incorporated plutonium

International Nuclear Information System (INIS)

Mikhail, S.

2004-01-01

Several epidemiological studies among workers of first Russian nuclear complex Mayak which produced weapon-grade plutonium showed significant increase of lung cancer mortality. The estimated shape of the dose-response was linear with both alpha and gamma dose but risk coefficients for gamma-exposure are on the edge of the significance level. This study was performed in the cohort of male Mayak nuclear workers initially hired in 1948-1958 with known levels of plutonium exposure. Number of observed lung cancer cases available for analyses in this cohort was 217. The relative risk of death from lung cancer among smokers was 10.7 (5.5-25.2) comparatively to non-smokers. This is in good correspondence with results of other studies. The excess relative risk per one Gray was 63. (4.1-9.7) for internal alpha-exposure and 0.18 (0.01-0.5) for external gamma-exposure. According to a model this gives 16:112:60:29 cases of lung cancer attributed to background, smoking, internal alpha-and external gamma-exposure, correspondingly. The relative risks of death from lung cancer were also estimated in a nested case-control study with lung cancer deaths as cases. Controls were selected from the cohort and matched for birth year to account for trend in lung cancer mortality with time. The analyses with nested case-control approach gave relative risks for smoking 14.7 (6.8-38.9). Relative risk of lung cancer among non-smokers after accumulating 0.34 Gy of alpha-exposure to lung was 3.7 (1.7-9.0). It should be emphasized that in fact after accumulation 0.3-0.4 Gy of absorbed dose 3-4 fold increase in lung cancer mortality was observed. This dose is very close to the dose which would be produced after intake of plutonium in quantities which are permissible today. (Author)

Bioaerosols from a Food Waste Composting Plant Affect Human Airway Epithelial Cell Remodeling Genes

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Chang, Ming-Wei; Lee, Chung-Ru; Hung, Hsueh-Fen; Teng, Kuo-Sheng; Huang, Hsin; Chuang, Chun-Yu

2013-01-01

The composting procedure in food waste plants generates airborne bioaerosols that have the potential to damage human airway epithelial cells. Persistent inflammation and repair responses induce airway remodeling and damage to the respiratory system. This study elucidated the expression changes of airway remodeling genes in human lung mucoepidermoid NCI-H292 cells exposed to bioaerosols from a composting plant. Different types of microorganisms were detectable in the composting plant, using the agar culture method. Real-time polymerase chain reaction was used to quantify the level of Aspergillus fumigatus and the profile of remodeling genes. The real-time PCR results indicated that the amount of A. fumigatus in the composting hall was less than 102 conidia. The endotoxins in the field bioaerosols were determined using a limulus amebocyte lysate test. The endotoxin levels depended on the type of particulate matter (PM), with coarse particles (2.5–10 μm) having higher endotoxin levels than did fine particles (0.5–2.5 μm). After exposure to the conditioned medium of field bioaerosol samples, NCI-H292 cells showed increased pro-inflammatory interleukin (IL)-6 release and activated epidermal growth factor receptor (EGFR), transforming growth factor (TGF)-β1 and cyclin-dependent kinase inhibitor 1 (p21WAF1/CIP1) gene expression, but not of matrix metallopeptidase (MMP)-9. Airborne endotoxin levels were higher inside the composting hall than they were in other areas, and they were associated with PM. This suggested that airborne bioaerosols in the composting plant contained endotoxins and microorganisms besides A. fumigatus that cause the inflammatory cytokine secretion and augment the expression of remodeling genes in NCI-H292 cells. It is thus necessary to monitor potentially hazardous materials from bioaerosols in food composting plants, which could affect the health of workers. PMID:24368426

Bioaerosols from a food waste composting plant affect human airway epithelial cell remodeling genes.

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Chang, Min-Wei; Lee, Chung-Ru; Hung, Hsueh-Fen; Teng, Kuo-Sheng; Huang, Hsin; Chuang, Chun-Yu

2013-12-24

The composting procedure in food waste plants generates airborne bioaerosols that have the potential to damage human airway epithelial cells. Persistent inflammation and repair responses induce airway remodeling and damage to the respiratory system. This study elucidated the expression changes of airway remodeling genes in human lung mucoepidermoid NCI-H292 cells exposed to bioaerosols from a composting plant. Different types of microorganisms were detectable in the composting plant, using the agar culture method. Real-time polymerase chain reaction was used to quantify the level of Aspergillus fumigatus and the profile of remodeling genes. The real-time PCR results indicated that the amount of A. fumigatus in the composting hall was less than 10(2) conidia. The endotoxins in the field bioaerosols were determined using a limulus amebocyte lysate test. The endotoxin levels depended on the type of particulate matter (PM), with coarse particles (2.5-10 μm) having higher endotoxin levels than did fine particles (0.5-2.5 μm). After exposure to the conditioned medium of field bioaerosol samples, NCI-H292 cells showed increased pro-inflammatory interleukin (IL)-6 release and activated epidermal growth factor receptor (EGFR), transforming growth factor (TGF)-β1 and cyclin-dependent kinase inhibitor 1 (p21 WAF1/CIP1) gene expression, but not of matrix metallopeptidase (MMP)-9. Airborne endotoxin levels were higher inside the composting hall than they were in other areas, and they were associated with PM. This suggested that airborne bioaerosols in the composting plant contained endotoxins and microorganisms besides A. fumigatus that cause the inflammatory cytokine secretion and augment the expression of remodeling genes in NCI-H292 cells. It is thus necessary to monitor potentially hazardous materials from bioaerosols in food composting plants, which could affect the health of workers.

Spine Metastases in Lung Cancer

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O.Yu. Stolyarova

2015-10-01

Full Text Available The purpose and the objectives of the study were to determine the incidence of metastatic lesions to various parts of the spine, the assessment of the association with other clinical signs of lung cancer (localization, form, histology, degree of differentiation, staging, nature of extraosseous metastasis, to investigate the effect of these parameters on the survi­val of the patients. Material and methods. The study included 1071 patients with lung cancer aged 24 to 86 years. None of the examined patients has been operated previously for lung cancer, and after arriving at a diagnosis, all patients received radiation therapy, 73 % of them — combined radiochemothe­rapy. Results. Metastasis in the vertebral bodies and vertebral joints occurs in 13 % of patients with lung cancer and in 61 % of patients with bone form of the disease, the ratio of the defeat of thoracic, sacral, lumbar and cervical spine was 6 : 4 : 2 : 1. The development of metastases in the spine is mostly associa­ted with the localization of the tumor in the upper lobe of the lung, the peripheral form of the disease, with non-small cell histologic variants (adenocarcinoma and squamous cell carcinoma. The number of metastases in the spinal column directly correlates with the degree of metastatic involvement of the inguinal lymph nodes, abdominal wall and the liver, has an impact on the invasion of lung tumor into the esophagus and the trachea. The life expectancy of the deceased persons with spine metastases is less than that of other patients with the lung cancer, but the overall survival rate in these groups of patients is not very different. Conclusions. Clinical features of lung cancer with metastases in the spine necessitate the development of medical technology of rational radiochemotherapy in such patients.

Detection of five tumor markers in lung cancer by trypsin digestion of sputum method

International Nuclear Information System (INIS)

Lin Min; Nong Tianlei; Liu Daying

2011-01-01

To explore the detection of five tumor markers by trypsin digestion of sputum in the diagnosis of lung cancer, the samples of sputum in patients with lung cancer and benign lung disease were digested by trypsin and used to measure five tumor markers. The results showed that the sputum were well digested by 6% trypsin at pH8 and no affect on the determination of tumor markers. The CEA, CA125, CA153, CA211 and NSE levels in lung cancer group were significantly higher than that of in benign group (P<0.05). The sputum CEA and CA125 levels were significantly higher than that of the serum levels (P<0.05). The detection of sputum CEA, CA125, CA153, CA211 and NSE levels have clinical value in the diagnosis of lung cancer. When combined with other diagnostic methods,it might be helpful for further diagnosis in non confirmed lung cancer patients. (authors)

Mortality and survival of lung cancer in Denmark: Results from the Danish Lung Cancer Group 2000-2012

DEFF Research Database (Denmark)

Jakobsen, Erik; Rasmussen, Torben Riis; Green, Anders

2016-01-01

Background In the 1990s outcomes in Danish lung cancer patients were poor compared with the other Nordic countries. The five-year survival was only about 5%, only 10% of patients were operated on and less than 60% received active surgical or oncologic treatment. This paper describes trends...... in mortality and survival of lung cancer in Denmark from 2000 to 2012. Methods The study population comprised 52 435 patients with a diagnosis of cancer of the trachea and the lung, primarily ascertained from the Danish Lung Cancer Register and grouped into three cohorts by year of diagnosis. The outcome...... for all strata by gender, comorbidity, stage and surgery status and was accompanied by corresponding improvements in both absolute and relative survival. Conclusions The mortality has been significantly declining and the prognosis correspondingly improving in lung cancer in Denmark since the turn...

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

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

2017-01-01

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

Metachronous Lung Cancer: Clinical Characteristics and Effects of Surgical Treatment.

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Rzechonek, Adam; Błasiak, Piotr; Muszczyńska-Bernhard, Beata; Pawełczyk, Konrad; Pniewski, Grzegorz; Ornat, Maciej; Grzegrzółka, Jędrzej; Brzecka, Anna

2018-01-01

The occurrence of a second lung tumor after surgical removal of lung cancer usually indicates a lung cancer metastasis, but sometimes a new lesion proves to be a new primary lung cancer, i.e., metachronous lung cancer. The goal of the present study was to conduct a clinical evaluation of patients with metachronous lung cancer and lung cancer metastasis, and to compare the early and distant outcomes of surgical treatment in both cancer types. There were 26 age-matched patients with lung cancer metastases and 23 patients with metachronous lung cancers, who underwent a second lung cancer resection. We evaluated the histological type of a resected cancer, the extent of thoracosurgery, the frequency of early postoperative complications, and the probability of 5-year survival after the second operation. The findings were that metachronous lung cancer was adenocarcinoma in 52% of patients, with a different histopathological pattern from that of the primary lung cancer in 74% of patients. In both cancer groups, mechanical resections were the most common surgery type (76% of all cases), with anatomical resections such as segmentectomy, lobectomy, or pneumectomy being much rarer conducted. The incidence of early postoperative complications in metachronous lung cancer and lung cancer metastasis (30% vs. 31%, respectively) and the probability of 5-year survival after resection of either cancer tumor (60.7% vs. 50.9%, respectively) were comparable. In conclusion, patients undergoing primary lung cancer surgery require a long-term follow-up due to the risk of metastatic or metachronous lung cancer. The likelihood of metachronous lung cancer and pulmonary lung cancer metastases, the incidence of postoperative complications, and the probability of 5-year survival after resection of metachronous lung cancer or lung cancer metastasis are similar.

Lung Cancer Screening (PDQ®)—Health Professional Version

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Lung cancer screening with low-dose spiral CT scans has been shown to decrease the risk of dying from lung cancer in heavy smokers. Screening with chest x-ray or sputum cytology does not reduce lung cancer mortality. Get detailed information about lung cancer screening in this clinician summary.

Nucleomedical diagnosis of lung cancer

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Ito, Yasuhiko [Kawasaki Medical School, Kurashiki, Okayama (Japan)

1982-06-01

/sup 67/Ga citrate is most often used in the diagnosis of lung cancer. As judged from reported cases, the accuracy rate was 90%, with a false negative rate being about 5%. Lung ventilation and blood flow scintigraphy are valuable in assessing the degree of damage to lung function and the therapeutic effect rather than in finding lung cancer. In aerosol scintigraphy, sup(99m)Tc labelled aerosols with different particle size depending on the purpose of diagnosis are used; the large particles deposit at the center of the trachea and small size aerosols on the periphery. Aerosol-inhaled scintigraphy is highly valuable for the diagnosis of hilus lung cancer. sup(99m)Tc methylene diphosphate is used in bone scintigraphy to detect bone metastasis. But it sometimes gives false positive results such as in the case of senile bone changes. Another valuable method of diagnosis is emission CT by which various substances having affinity for the tumor can be detected by labelling them with a proton emitting nuclear species such as 11 C, /sup 13/N, /sup 15/O and /sup 18/F. Some cases of lung cancer, and the radionuclide methods used in the diagnosis are shown.

Cytotoxic Effects of Fascaplysin against Small Cell Lung Cancer Cell Lines

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Gerhard Hamilton

2014-03-01

Full Text Available Fascaplysin, the natural product of a marine sponge, exhibits anticancer activity against a broad range of tumor cells, presumably through interaction with DNA, and/or as a highly selective cyclin-dependent kinase 4 (CDK4 inhibitor. In this study, cytotoxic activity of fascaplysin against a panel of small cell lung cancer (SCLC cell lines and putative synergism with chemotherapeutics was investigated. SCLC responds to first-line chemotherapy with platinum-based drugs/etoposide, but relapses early with topotecan remaining as the single approved therapeutic agent. Fascaplysin was found to show high cytotoxicity against SCLC cells and to induce cell cycle arrest in G1/0 at lower and S-phase at higher concentrations, respectively. The compound generated reactive oxygen species (ROS and induced apoptotic cell death in the chemoresistant NCI-H417 SCLC cell line. Furthermore, fascaplysin revealed marked synergism with the topoisomerase I-directed camptothecin and 10-hydroxy-camptothecin. The Poly(ADP-ribose-Polymerase 1 (PARP1 inhibitor BYK 204165 antagonized the cytotoxic activity of fascaplysin, pointing to the involvement of DNA repair in response to the anticancer activity of the drug. In conclusion, fascaplysin seems to be suitable for treatment of SCLC, based on high cytotoxic activity through multiple routes of action, affecting topoisomerase I, integrity of DNA and generation of ROS.

Discovery – The Link to H.Pylori Bacteria

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NCI supported research to solidify the link between H. pylori infections and stomach cancer. As a result, new cancer treatment and prevention strategies are being developed, encouraging scientists to carefully examine other cancers for viral and bacterial connections.

Lung Cancer Screening (PDQ®)—Patient Version

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Lung cancer screening with low-dose spiral CT scans has been shown to decrease the risk of dying from lung cancer in heavy smokers. Learn more about tests to detect lung cancer and their potential benefits and harms in this expert-reviewed summary.

Parity and risk of lung cancer in women.

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Paulus, Jessica K; Asomaning, Kofi; Kraft, Peter; Johnson, Bruce E; Lin, Xihong; Christiani, David C

2010-03-01

Patterns of lung cancer incidence suggest that gender-associated factors may influence lung cancer risk. Given the association of parity with risk of some women's cancers, the authors hypothesized that childbearing history may also be associated with lung cancer. Women enrolled in the Lung Cancer Susceptibility Study at Massachusetts General Hospital (Boston, Massachusetts) between 1992 and 2004 (1,004 cases, 848 controls) were available for analysis of the association between parity and lung cancer risk. Multivariate logistic regression was used to estimate adjusted odds ratios and 95% confidence intervals. After results were controlled for age and smoking history, women with at least 1 child had 0.71 times the odds of lung cancer as women without children (odds ratio = 0.71, 95% confidence interval: 0.52, 0.97). A significant linear trend was found: Lung cancer risk decreased with increasing numbers of children (P < 0.001). This inverse association was stronger in never smokers (P = 0.12) and was limited to women over age 50 years at diagnosis (P = 0.17). Age at first birth was not associated with risk. The authors observed a protective association between childbearing and lung cancer, adding to existing evidence that reproductive factors may moderate lung cancer risk in women.

Radionuclide molecular target therapy for lung cancer

International Nuclear Information System (INIS)

Zhang Fuhai; Meng Zhaowei; Tan Jian

2012-01-01

Lung cancer harms people's health or even lives severely. Currently, the morbidity and mortality of lung cancer are ascending all over the world. Accounting for 38.08% of malignant tumor caused death in male and 16% in female in cities,ranking top in both sex. Especially, the therapy of non-small cell lung cancer has not been obviously improved for many years. Recently, sodium/iodide transporter gene transfection and the therapy of molecular target drugs mediated radionuclide are being taken into account and become the new research directions in treatment of advanced lung cancer patients with the development of technology and theory for medical molecular biology and the new knowledge of lung cancer's pathogenesis. (authors)

TP53 Mutations in Nonsmall Cell Lung Cancer

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Akira Mogi

2011-01-01

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

CT imaging of coexisting pulmonary tuberculosis and lung cancer

International Nuclear Information System (INIS)

Lv Yan; Xie Ruming; Zhou Xinhua; Zhou Zhen; Xu Jinping; He Wei; Guo Lifang; Ning Fenggang

2013-01-01

Objective: To study the CT characteristics of coexisting pulmonary tuberculosis and lung cancer. Methods: One hundred and four patients of coexisting pulmonary tuberculosis and lung cancer proved by histology, cytology or clinical underwent CT examination. All patients were divided into two groups, group Ⅰ were the patients with the lung cancer after tuberculosis or both found simultaneously (group Ⅰ a with peripheral lung cancer and group Ⅰ b with central lung cancer), group Ⅱ with tuberculosis during lung cancer chemotherapy (group Ⅱ a with peripheral lung cancer and group Ⅱ b with central lung cancer). Imaging characteristics of tuberculosis and lung cancer were compared. χ"2 test and t test were used for the statistical analysis. Results: Of 104 patients, there were 92 patients (88.5%) in group Ⅰ and 12 patients (11.5%) in group Ⅱ. Seventy patients (76.1%) of lung cancer and tuberculosis were located in the same lobe and 22 patients (23.9%) in the different lobes in group Ⅰ. There was no significant difference in distribution of tuberculosis between group Ⅰ and group Ⅱ (χ"2 = 4.302, P = 0.507). The fibrous stripes, nodules of calcification and pleural adhesion of tuberculosis were statistically significant between the two groups (χ"2 = 22.737, 15.193, 27.792, P < 0.05). There were 33 central lung cancers and 71 peripheral lung cancers. In group Ⅰ a (64 patients of peripheral lung cancers), 39 patients (60.9%) had typical manifestations and most of the lesions were ≥ 3 cm (n = 49, 76.6%), solid lesions showed variable enhancement. Conclusions: Secondary tuberculosis during lung cancer chemotherapy has the same CT characteristics with the common active tuberculosis. The morphology, enhancement pattern of lesion and follow-up are helpful for the diagnosis of lung cancer after tuberculosis. (authors)

Nationwide quality improvement in lung cancer care

DEFF Research Database (Denmark)

Jakobsen, Erik Winther; Green, Anders; Oesterlind, Kell

2013-01-01

To improve prognosis and quality of lung cancer care the Danish Lung Cancer Group has developed a strategy consisting of national clinical guidelines and a clinical quality and research database. The first edition of our guidelines was published in 1998 and our national lung cancer registry...... was opened for registrations in 2000. This article describes methods and results obtained by multidisciplinary collaboration and illustrates how quality of lung cancer care can be improved by establishing and monitoring result and process indicators....

[Landscape of Lung Cancer with Oligometastasis].

Science.gov (United States)

Goto, Yasushi; Sato, Jun

2017-10-01

Lung cancer with a few to several metastases is so-called oligometastatic disease. Patient with recurrence only to limited site is also known as oligo-recurrence, and may be included as oligometastatic disease. From biological aspect, any existence of metastases is a sign of systemic disease. Due to the reports of long survival with only local treatment and without systemic disease in oligometastatic lung cancer, word of oligometastasis is used with fascinating expectation of cure to advanced lung cancer. Most of the previous reports are retrospective and no comprehensive data exists for selecting patient for local treatment to oligometastasis. Recent positive result of randomize phase II study is followed up with phase III study. Progress in treatment of advanced non-small cell lung cancer with targeted therapy to oncogenic-driver(EGFR, ALK, ROS1 and others) and immune-checkpoint inhibitor(PD-1 pathway inhibitors)makes it difficult to define the appropriate indication of local treatment to oligometastatic lung cancer.

Comparison of the prevalence of malnutrition diagnosis in head and neck, gastrointestinal and lung cancer patients by three classification methods

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Platek, Mary E.; Popp KPf, Johann V.; Possinger, Candi S.; DeNysschen, Carol A.; Horvath, Peter; Brown, Jean K.

2011-01-01

Background Malnutrition is prevalent among patients within certain cancer types. There is lack of universal standard of care for nutrition screening, lack of agreement on an operational definition and on validity of malnutrition indicators. Objective In a secondary data analysis, we investigated prevalence of malnutrition diagnosis by three classification methods using data from medical records of a National Cancer Institute (NCI)-designated comprehensive cancer center. Interventions/Methods Records of 227 patients hospitalized during 1998 with head and neck, gastrointestinal or lung cancer were reviewed for malnutrition based on three methods: 1) physician diagnosed malnutrition related ICD-9 codes; 2) in-hospital nutritional assessment summary conducted by Registered Dietitians; and 3) body mass index (BMI). For patients with multiple admissions, only data from the first hospitalization was included. Results Prevalence of malnutrition diagnosis ranged from 8.8% based on BMI to approximately 26% of all cases based on dietitian assessment. Kappa coefficients between any methods indicated a weak (kappa=0.23, BMI and Dietitians and kappa=0.28, Dietitians and Physicians) to fair strength of agreement (kappa=0.38, BMI and Physicians). Conclusions Available methods to identify patients with malnutrition in an NCI designated comprehensive cancer center resulted in varied prevalence of malnutrition diagnosis. Universal standard of care for nutrition screening that utilizes validated tools is needed. Implications for Practice The Joint Commission on the Accreditation of Healthcare Organizations requires nutritional screening of patients within 24 hours of admission. For this purpose, implementation of a validated tool that can be used by various healthcare practitioners, including nurses, needs to be considered. PMID:21242767

Peptide hormones and lung cancer.

Science.gov (United States)

Moody, T W

2006-03-01

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

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

International Nuclear Information System (INIS)

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

2012-01-01

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

[Development of the lung cancer diagnostic system].

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Lv, You-Jiang; Yu, Shou-Yi

2009-07-01

To develop a lung cancer diagnosis system. A retrospective analysis was conducted in 1883 patients with primary lung cancer or benign pulmonary diseases (pneumonia, tuberculosis, or pneumonia pseudotumor). SPSS11.5 software was used for data processing. For the relevant factors, a non-factor Logistic regression analysis was used followed by establishment of the regression model. Microsoft Visual Studio 2005 system development platform and VB.Net corresponding language were used to develop the lung cancer diagnosis system. The non-factor multi-factor regression model showed a goodness-of-fit (R2) of the model of 0.806, with a diagnostic accuracy for benign lung diseases of 92.8%, a diagnostic accuracy for lung cancer of 89.0%, and an overall accuracy of 90.8%. The model system for early clinical diagnosis of lung cancer has been established.

NCI intramural research highlighted at 2014 AACR meeting

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This year’s American Association for Cancer Research meeting featured plenary talks by two NCI scientists, Steven Rosenberg, M.D., and Louis Staudt, M.D., Ph.D., that highlighted the challenges in developing varied and potentially synergistic treatments f

Anti-cancer activity of tectona hamiltoniana-an endemic plant of Myanmar

International Nuclear Information System (INIS)

Mya, K.M.; Shyaula, S.L.

2012-01-01

Summary: The ethanolic extracts of barks and leaves of Tectona hamiltoniana (Verbenaceae) were tested for anti-cancer activity against MCF-7 (Human breast cancer) and NCI-H460 (Lung cancer) cell lines employing sulpho rhodamine B (SRB) bioassay. These extracts demonstrated cytotoxicity with GI/sub 50/ values ranging between 24-33 macro g/mL against both cell lines. Upon further fractionation, dichloromethane fraction appeared to be most active against the MCF-7 cell line (GI/sub 50/ value of 3.4+-0.9 macro g/mL) leading to the isolation of lupane type triterpenoids, betulinic acid (1), betulin aldehyde ( 2 ) and betulin (3). Compound 2 and 3, both showed significant cytotoxic effect against both cancerous cell lines (GI/sub 50/ value range 6-11 macro M). (author)

Icotinib: activity and clinical application in Chinese patients with lung cancer.

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Guan, Yong-Song; He, Qing; Li, Mei

2014-04-01

Icotinib (BPI-2009H, Conmana) is a novel oral quinazoline compound that has proven survival benefit in Chinese patients with lung cancer, for which several therapies are currently available often with unsatisfactory results. Icotinib is the first self-developed small molecular drug in China for targeted therapy of lung cancer. The authors' experience in the clinical application of icotinib is reviewed in combination with related publications in the literature. Antitumor activities were observed in non-small-cell lung cancer and others in several recent studies. On 7 June 2011, icotinib was approved by the State Food and Drug Administration of China for the treatment of local advanced or metastatic non-small-cell lung cancer based on the results of a nationwide, of 27 centers, randomized, double-blind, double-modulated, parallel-controlled, Phase III trial with single agent icotinib in lung cancer patients after failure of chemotherapy. Icotinib is a generic drug. Compared to the other two commercially available EGFR tyrosine kinase inhibitors, gefitinib and erlotinib, icotinib is similar to them in chemical structure, mechanism of activity and therapeutic effects but less expensive. Better safety as well as a wider therapeutic window has also been proven in several Chinese studies. Future studies on cost effectiveness are warranted.

Effects of Monoclonal Antibody Cetuximab on Proliferation of Non-small Cell Lung Cancer Cell lines

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Zhen CHEN

2010-08-01

Full Text Available Background and objective The epidermal growth factor receptor (EGFR monoclonal antibody cetuximab has been used widely in non-small cell lung cancer patients. The aim of this study is to explore the effect of lung cancer cells (A549, H460, H1299, SPC-A-1 which were treated by cetuximab in vitro. Methods We studied the effects of increasing concentrations of cetuximab (1 nmol/L-625 nmol/L in four human lung cancer cell lines (A549, SPC-A-1, H460, H1229. CCK8 measured the inhibition of cell proliferation in each group. A549, SPC-A-1 were marked by PI and the statuses of apoptosis were observed. Western blot were used to detect the proliferation-related signaling protein and apoptosis-related protein in A549. Results The treatment with cetuximab resulted in the effect on cell proliferation and apoptosis in a time- and dosedependent manner. The expression of activated key enzymes (p-AKT, p-EGFR, p-MAPK in EGFR signaling transduction pathway were down-regulated more obviously. Conclusion Cetuximab is an effective targeted drug in the treatment of lung cancer cell lines, tissues, most likely to contribute to the inhibition of key enzymes in EGFR signaling transduction pathway.

Proton Beam Therapy of Stage II and III Non–Small-Cell Lung Cancer

International Nuclear Information System (INIS)

Nakayama, Hidetsugu; Satoh, Hiroaki; Sugahara, Shinji; Kurishima, Koichi; Tsuboi, Koji; Sakurai, Hideyuki; Ishikawa, Shigemi; Tokuuye, Koichi

2011-01-01

Purpose: The present retrospective study assessed the role of proton beam therapy (PBT) in the treatment of patients with Stage II or III non–small-cell lung cancer who were inoperable or ineligible for chemotherapy because of co-existing disease or refusal. Patients and Methods: Between November 2001 and July 2008, PBT was given to 35 patients (5 patients with Stage II, 12 with Stage IIIA, and 18 with Stage IIIB) whose median age was 70.3 years (range, 47.4–85.4). The median proton dose given was 78.3 Gy (range, 67.1–91.3) (relative biologic effectiveness). Results: Local progression-free survival for Stage II-III patients was 93.3% at 1 year and 65.9% at 2 years during a median observation period of 16.9 months. Four patients (11.4%) developed local recurrence, 13 (37.1%) developed regional recurrence, and 7 (20.0%) developed distant metastases. The progression-free survival rate for Stage II-III patients was 59.6% at 1 year and 29.2% at 2 years. The overall survival rate of Stage II-III patients was 81.8% at 1 year and 58.9% at 2 years. Grade 3 or greater toxicity was not observed. A total of 15 patients (42.9%) developed Grade 1 and 6 (17.1%) Grade 2 toxicity. Conclusion: PBT for Stage II-III non–small-cell lung cancer without chemotherapy resulted in good local control and low toxicity. PBT has a definite role in the treatment of patients with Stage II-III non–small-cell lung cancer who are unsuitable for surgery or chemotherapy.

Proton Beam Therapy of Stage II and III Non-Small-Cell Lung Cancer

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Nakayama, Hidetsugu, E-mail: hnakayam@tokyo-med.ac.jp [Proton Medical Research Center, University of Tsukuba Graduate School of Comprehensive Human Sciences, Tsukuba, Ibaraki (Japan); Department of Radiation Oncology, Tokyo Medical University, Shinjuku, Tokyo (Japan); Satoh, Hiroaki [Department of Respiratory Medicine, University of Tsukuba Graduate School of Comprehensive Human Sciences, Tsukuba, Ibaraki (Japan); Sugahara, Shinji [Proton Medical Research Center, University of Tsukuba Graduate School of Comprehensive Human Sciences, Tsukuba, Ibaraki (Japan); Department of Radiation Oncology, Tokyo Medical University, Shinjuku, Tokyo (Japan); Kurishima, Koichi [Department of Respiratory Medicine, University of Tsukuba Graduate School of Comprehensive Human Sciences, Tsukuba, Ibaraki (Japan); Tsuboi, Koji; Sakurai, Hideyuki [Proton Medical Research Center, University of Tsukuba Graduate School of Comprehensive Human Sciences, Tsukuba, Ibaraki (Japan); Ishikawa, Shigemi [Department of Thoracic Surgery, University of Tsukuba Graduate School of Comprehensive Human Sciences, Tsukuba, Ibaraki (Japan); Tokuuye, Koichi [Proton Medical Research Center, University of Tsukuba Graduate School of Comprehensive Human Sciences, Tsukuba, Ibaraki (Japan); Department of Radiation Oncology, Tokyo Medical University, Shinjuku, Tokyo (Japan)

2011-11-15

Purpose: The present retrospective study assessed the role of proton beam therapy (PBT) in the treatment of patients with Stage II or III non-small-cell lung cancer who were inoperable or ineligible for chemotherapy because of co-existing disease or refusal. Patients and Methods: Between November 2001 and July 2008, PBT was given to 35 patients (5 patients with Stage II, 12 with Stage IIIA, and 18 with Stage IIIB) whose median age was 70.3 years (range, 47.4-85.4). The median proton dose given was 78.3 Gy (range, 67.1-91.3) (relative biologic effectiveness). Results: Local progression-free survival for Stage II-III patients was 93.3% at 1 year and 65.9% at 2 years during a median observation period of 16.9 months. Four patients (11.4%) developed local recurrence, 13 (37.1%) developed regional recurrence, and 7 (20.0%) developed distant metastases. The progression-free survival rate for Stage II-III patients was 59.6% at 1 year and 29.2% at 2 years. The overall survival rate of Stage II-III patients was 81.8% at 1 year and 58.9% at 2 years. Grade 3 or greater toxicity was not observed. A total of 15 patients (42.9%) developed Grade 1 and 6 (17.1%) Grade 2 toxicity. Conclusion: PBT for Stage II-III non-small-cell lung cancer without chemotherapy resulted in good local control and low toxicity. PBT has a definite role in the treatment of patients with Stage II-III non-small-cell lung cancer who are unsuitable for surgery or chemotherapy.

Lung cancer-associated tumor antigens and the present status of immunotherapy against non-small-cell lung cancer

International Nuclear Information System (INIS)

Yasumoto, Kosei; Hanagiri, Takeshi; Takenoyama, Mitsuhiro

2009-01-01

Despite recent advances in surgery, irradiation, and chemotherapy, the prognosis of patients with lung cancer is still poor. Therefore, the development and application of new therapeutic strategies are essential for improving the prognosis of this disease. Significant progress in our understanding of tumor immunology and molecular biology has allowed us to identify the tumor-associated antigens recognized by cytotoxic T lymphocytes. Immune responses and tumor-associated antigens against not only malignant melanoma but also lung cancer have been elucidated at the molecular level. In a theoretical sense, tumor eradication is considered possible through antigen-based immunotherapy against such diseases. However, many clinical trials of cancer vaccination with defined tumor antigens have resulted in objective clinical responses in only a small number of patients. Tumor escape mechanisms from host immune surveillance remain a major obstacle for cancer immunotherapy. A better understanding of the immune escape mechanisms employed by tumor cells is necessary before we can develop a more effective immunotherapeutic approach to lung cancer. We review recent studies regarding the identification of tumor antigens in lung cancer, tumor immune escape mechanisms, and clinical vaccine trials in lung cancer. (author)

Lung cancer symptoms and pulse oximetry in the prognostic assessment of patients with lung cancer

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Harada Cecilia M

2005-07-01

Full Text Available Abstract Background Medical oncologists continue to use performance status as a proxy for quality of life (QOL measures, as completion of QOL instruments is perceived as time consuming, may measure aspects of QOL not affected by cancer therapy, and interpretation may be unclear. The pulse oximeter is widely used in clinical practice to predict cardiopulmonary morbidity after lung resection in cancer patients, but little is known on its role outside the surgical setting. We evaluated whether the Lung Cancer Symptom Scale and pulse oximetry may contribute to the evaluation of lung cancer patients who received standard anticancer therapy. Methods We enrolled forty-one consecutive, newly diagnosed, patients with locally advanced or metastatic lung cancer in this study. We developed a survival model with the variables gender, age, histology, clinical stage, Karnofsky performance status, wasting, LCSS symptom scores, average symptom burden index, and pulse oximetry (SpO2. Results Patient and observer-rated scores were correlated, except for the fatigue subscale. The median SpO2 was 95% (range: 86 to 98, was unrelated to symptom scores, and was weakly correlated with observer cough scores. In a multivariate survival model, SpO2 > 90% and patient scores on the LCSS appetite and fatigue subscales were independent predictors of survival. Conclusion LCSS fatigue and appetite rating, and pulse oximetry should be studied further as prognostic factors in lung cancer patients.

Lung cancer

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... causing chemicals such as uranium, beryllium, vinyl chloride, nickel chromates, coal products, mustard gas, chloromethyl ethers, gasoline, and diesel exhaust Exposure to radon gas Family history of lung cancer ...

Lung cancer in the Kashmir valley

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Koul Parvaiz

2010-01-01

Full Text Available Background: Lung cancer has been found to be the second commonest cancer according to a hospital-based data from Kashmir, India. However, no incidence studies are available. Objective: To ascertain the incidence of lung cancer in Kashmir. Materials and Methods: All newly histologically diagnosed cases of lung cancer seen in various hospital and private laboratories of the Kashmir valley were registered over a period of two years (January 1, 2004 to December 31, 2005. Also included were patients attending the various oncological service areas of the institute and those diagnosed from any other laboratory outside the state. The incidence rate was calculated using the January 2005 population as the reference population estimated using the census-based projected populations. Results: Four hundred and sixty-two incident cases of lung cancer were seen during the study period. The crude incidence rate, age standardized (world and truncated age adjusted (40-69 years, world incidence rates for lung cancer per 100 000 population were 4.01, 6.48 and 15.28 respectively (males 6.55, 10.09 and 23.94 respectively and females 1.19, 2.14 and 4.65. The age adjusted rates for males in district Srinagar was 19.34 per 100 000. One hundred and fifty nine (69.8% of the 221 had a history of Hukkah smoking. Conclusions: Even though Kashmir as a whole is a low incidence area for lung cancer (ASR of < 15, Srinagar district has the highest incidence of lung cancer among the males in Kashmir. The data presented is assumed to be the closest approximation to a population-based data registry and the geographical incidence maps of ICMR need appropriate updating

Lung Cancer Screening

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... detected on a lung CT scan. If your doctor finds another health problem, you may undergo further testing and, possibly, invasive treatments that wouldn't have been pursued if you hadn't had lung cancer ... need to: Inform your doctor if you have a respiratory tract infection. If ...

Acute exacerbation of idiopathic interstitial pneumonia complicated by lung cancer, caused by treatment for lung cancer

International Nuclear Information System (INIS)

Takenaka, Kiyoshi; Okano, Tetsuya; Yoshimura, Akinobu

1999-01-01

In 64 patients with lung cancer complicated by idiopathic interstitial pneumonia (IIP), we retrospectively studied the outcome of the treatment for lung cancer and clinical features of acute exacerbation of IIP after treatment for lung cancer. The incidence of acute exacerbation of IIP was 8.7% (2 of 23 patients) after anticancer chemotherapy, 14.3% (2 of 14 patients) after operation, and 25% (2 of 8 patients) after radiation therapy. Serum C-reactive protein level was significantly higher in the patients who developed acute exacerbation of IIP than in those who did not (CRP=5.12±2.27, 2.26±2.29, respectively). On the contrary, there were no differences in the levels of serum lactate dehydrogenase, white blood cell count, erythrocyte sedimentation rate, PaO 2 , and %VC between the two groups. Pathologic presentations of surgically resected lungs did not show significant differences in the activity of IIP between the two groups. Five of 6 patients who developed acute exacerbation of IIP died within 3 months after the treatment for lung cancer. We conclude that we should evaluate the activity of IIP more precisely using new markers for activity of IIP and on that basis select patients to be treated for lung cancer. (author)

Surgical management of non-small-cell lung cancer

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Bamousa Ahmed

2008-10-01

Full Text Available Surgery plays a major role in the management of patients with lung cancer. Surgery is not only the main curative treatment modality in patients with early-stage lung cancer but it also has a significant role in the initial workup for the diagnosis and staging of lung cancer. This article describes the surgical management of patients with lung cancer. Surgical resection for lung cancer is still regarded as the most effective method for controlling the primary tumor, provided it is resectable for cure and the risks of the procedure are low. The 5-year survival rare following complete resection (R0 of a lung cancer is stage dependent [Table 1]. [1-3] Incomplete resection (R1, R2 rarely, if ever, cures the patient.

Concerns About Lung Cancer Among Prisoners.

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Renault, Luc; Perrot, Emmanuel; Pradat, Eric; Bartoli, Christophe; Greillier, Laurent; Remacle-Bonnet, Anne; Telmon, Norbert; Mazières, Julien; Molinier, Laurent; Couraud, Sébastien

2018-02-01

Few studies have looked at lung cancer in prisoners, despite this population is possibly at increased risk of malignancy. In a previous study, we found an early onset of lung cancer in prisoners. Thus, the present CARCAN study was aimed at assessing the epidemiological characteristics, management, prognosis, and incidence of lung cancer in prisoners compared to a sample of non-prisoner patients. We performed a multi-center observational case-control study. Cases were prisoners diagnosed with lung cancer from 2005 to 2013. Controls were non-prisoner lung cancer patients selected from hospital databases and randomly matched to cases (targeted case-control ratio: 1:3). Incidence rates in both groups were calculated using national statistics. Seventy-two cases and 170 controls met inclusion criteria. Cases were mainly men (99%). Mean age at diagnosis was 52.9 (± 11.0) in cases and 64.3 (± 10.1) in controls (p < 0.0001). More case patients were current smokers compared to control patients (83% vs 53%; p < 0.0001). We found no significant differences between the two groups as concerns histologic types, TNM stages at diagnosis, initially-employed treatments, times to management or survival. Incidence rates (2008-2012) in male prisoners were higher than those in the general population in all concerned age groups. There is a shift of lung cancer toward young people in prisons. However, the presentation, management, and prognosis of lung cancer are similar between prisoners and non-prisoners. These finding could justify a specific screening policy for the incarcerated populations.

College Graduate with NCI Internship Gains Experience, Carries Chemistry into Medicine | Poster

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For Jennifer Marshall, the skills learned through an internship at the National Cancer Institute (NCI) at Frederick have prepared her for the next step of her life—medical school. Marshall, who will be attending the West Virginia University School of Medicine in the fall, spent three summers in NCI at Frederick’s Summer Internship Program expanding her love and passion for

The utilization of websites for fundraising by NCI-designated cancer centers: Examining the capacity for dialogic communication with prospective donors.

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Erwin, Cathleen O; Dias, Ashley M

2016-01-01

The study employs a dialogic public relations framework to explore the utilization of the Internet for fundraising by nonprofit health care organizations-specifically, NCI-designated cancer centers. Cancer centers have been noted for effective websites and for being highly engaged in fundraising, which is characterized as relationship marketing. Results indicate all but one cancer center use websites and social media for fundraising but are limited in capacity for two-way symmetrical dialogue. Results are discussed and recommendations are made for future research.

The Azygous Lobe of the Lung: in the Case of Lung Cancer.

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Darlong, L M; Ram, Dharma; Sharma, Ashwani; Sharma, Anil Kumar; Iqbal, Sayed Assif; Nagar, Anand; Hazarika, Dibyamohan

2017-06-01

The azygous lobe of the lung is an uncommon developmental anomaly. Its surgical importance is hardly being described in literature. Here, we are presenting a case of lung cancer with incidental azygous lobe, with its surgical relevance during lung cancer surgery.

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

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

2017-01-01

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

[Survey and analysis of awareness of lung cancer prevention and control in a LDCT lung cancer screening project in Tianjin Dagang Oilfield of China].

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Ren, Guanhua; Ye, Jianfei; Fan, Yaguang; Wang, Jing; Sun, Zhijuan; Jia, Hui; Du, Xinxin; Hou, Chaohua; Wang, Ying; Zhao, Yongcheng; Zhou, Qinghua

2014-02-01

It has been proven that increase of the awareness level of lung cancer prevention and control could enhance participation of lung cancer screening of lung cancer high risk group. The aim of this study is to investigate the awareness level of lung cancer prevention and control and the effect of individual characteristics on lung cancer awareness, and to provide evidence for comprehensive lung cancer prevention in high risk areas of lung cancer. Staffs of Tianjin Dagang Oil Field who participate low dose CT (LDCT) lung cancer screening by cluster sampling or according to voluntary principle were surveyed, data of lung cancer awareness were collected by questionnaire. A total of 1,633 valid questionnaires were collected. The average age of respondents was 60.08±6.58. Most participants were males (82.2%) while female only accounted for 17.8%. The proportions of awareness about lung cancer in China, risk factors, screening methods and the knowledge of health examination were 64.5%, 77.1%, 43.7%, 49.6% respectively. Result of multiple logistic regression analysis showed that education level, smoking (pack-year), age, prior tuberculosis were the influencing factors of lung cancer awareness with adjusted Ors for education and age level as of 0.567 (95%CI: 0.439-0.733) and 1.373 (95%CI: 1.084-1.739) respectively. 80.3% of the participants can accept health examination once a year, while the ability to pay the medical expenses was not high. The influencing factors of health examination willingness were gender, age, income, the knowledge of lung cancer. Education level and smoking affect the awareness of lung cancer prevention and control, health education for lung cancer should be conducted especially in population with low education level. Comprehensive lung cancer control in high risk areas should combined lung cancer screening, tobacco control and health education.

Uncovering growth-suppressive MicroRNAs in lung cancer

DEFF Research Database (Denmark)

Liu, Xi; Sempere, Lorenzo F; Galimberti, Fabrizio

2009-01-01

PURPOSE: MicroRNA (miRNA) expression profiles improve classification, diagnosis, and prognostic information of malignancies, including lung cancer. This study uncovered unique growth-suppressive miRNAs in lung cancer. EXPERIMENTAL DESIGN: miRNA arrays were done on normal lung tissues...... and adenocarcinomas from wild-type and proteasome degradation-resistant cyclin E transgenic mice to reveal repressed miRNAs in lung cancer. Real-time and semiquantitative reverse transcription-PCR as well as in situ hybridization assays validated these findings. Lung cancer cell lines were derived from each......-malignant human lung tissue bank. RESULTS: miR-34c, miR-145, and miR-142-5p were repressed in transgenic lung cancers. Findings were confirmed by real-time and semiquantitative reverse transcription-PCR as well as in situ hybridization assays. Similar miRNA profiles occurred in human normal versus malignant lung...

Robert Wiltrout Says Goodbye to NCI in 2015 | Poster

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After 34 years at NCI, Robert Wiltrout, Ph.D., said he is looking forward to trading his I-270 commute for another type of commute: exploring the waterways of Maryland, Alaska, and Wyoming to fulfill his love of fishing. Wiltrout officially retired as director of the NCI Center for Cancer Research (CCR) on July 2 of last year. Throughout his college academic career, Wiltrout had an interest in science, but it was not until he was working on a research project for his master’s degree that he considered a career in scientific research.

Disseminated lung cancer presenting as a rectal mass

DEFF Research Database (Denmark)

Noergaard, Mia M; Stamp, Inger M H; Bodtger, Uffe

2016-01-01

Primary lung cancer is the leading cause of cancer-related deaths globally, and approximately 50% had metastatic disease at the time of diagnosis. A rectal mass and unintended weight loss are common manifestations of rectal cancer. Our case presented with a rectal mass, but workup revealed...... a metastatic lesion from lung cancer. Lung cancer metastases to the lower gastrointestinal tract imply reduced survival compared with the already poor mean survival of stage IV lung cancer. Despite relevant therapy, the patient died 5 months after referral....

Risk of second primary lung cancer in women after radiotherapy for breast cancer

International Nuclear Information System (INIS)

Grantzau, Trine; Thomsen, Mette Skovhus; Væth, Michael; Overgaard, Jens

2014-01-01

Background: Several epidemiological studies have reported increased risks of second lung cancers after breast cancer irradiation. In this study we assessed the effects of the delivered radiation dose to the lung and the risk of second primary lung cancer. Methods: We conducted a nested case–control study of second lung cancer in a population based cohort of 23,627 early breast cancer patients treated with post-operative radiotherapy from 1982 to 2007. The cohort included 151 cases diagnosed with second primary lung cancer and 443 controls. Individual dose-reconstructions were performed and the delivered dose to the center of the second lung tumor and the comparable location for the controls were estimated, based on the patient specific radiotherapy charts. Results: The median age at breast cancer diagnosis was 54 years (range 34–74). The median time from breast cancer treatment to second lung cancer diagnosis was 12 years (range 1–26 years). 91% of the cases were categorized as ever smokers vs. 40% among the controls. For patients diagnosed with a second primary lung cancer five or more years after breast cancer treatment the rate of lung cancer increased linearly with 8.5% per Gray (95% confidence interval = 3.1–23.3%; p < 0.001). This rate was enhanced for ever smokers with an excess rate of 17.3% per Gray (95% CI = 4.5–54%; p < 0.005). Conclusions: Second lung cancer after radiotherapy for early breast cancer is associated with the delivered dose to the lung. Although the absolute risk is relative low, the growing number of long-time survivors after breast cancer treatment highlights the need for advances in normal tissue sparing radiation techniques

DNA fingerprinting of the NCI-60 cell line panel.

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Lorenzi, Philip L; Reinhold, William C; Varma, Sudhir; Hutchinson, Amy A; Pommier, Yves; Chanock, Stephen J; Weinstein, John N

2009-04-01

The National Cancer Institute's NCI-60 cell line panel, the most extensively characterized set of cells in existence and a public resource, is frequently used as a screening tool for drug discovery. Because many laboratories around the world rely on data from the NCI-60 cells, confirmation of their genetic identities represents an essential step in validating results from them. Given the consequences of cell line contamination or misidentification, quality control measures should routinely include DNA fingerprinting. We have, therefore, used standard DNA microsatellite short tandem repeats to profile the NCI-60, and the resulting DNA fingerprints are provided here as a reference. Consistent with previous reports, the fingerprints suggest that several NCI-60 lines have common origins: the melanoma lines MDA-MB-435, MDA-N, and M14; the central nervous system lines U251 and SNB-19; the ovarian lines OVCAR-8 and OVCAR-8/ADR (also called NCI/ADR); and the prostate lines DU-145, DU-145 (ATCC), and RC0.1. Those lines also show that the ability to connect two fingerprints to the same origin is not affected by stable transfection or by the development of multidrug resistance. As expected, DNA fingerprints were not able to distinguish different tissues-of-origin. The fingerprints serve principally as a barcodes.

Pleiotropic effects of cancer cells' secreted factors on human stromal (mesenchymal) stem cells

DEFF Research Database (Denmark)

Al-toub, Mashael; Almusa, Abdulaziz; Almajed, Mohammed

2013-01-01

cells' secreted factors as represented by a panel of human cancer cell lines (breast (MCF7 and MDA-MB-231); prostate (PC-3); lung (NCI-H522); colon (HT-29) and head & neck (FaDu)) on the biological characteristics of MSCs. METHODS: Morphological changes were assessed using fluorescence microscopy......, but not from MCF7 and HT-29, developed an elongated, spindle-shaped morphology with bipolar processes. In association with phenotypic changes, genome-wide gene expression and bioinformatics analysis revealed an enhanced pro-inflammatory response of those MSCs. Pharmacological inhibitions of FAK and MAPKK...

The Danish randomized lung cancer CT screening trial

DEFF Research Database (Denmark)

Pedersen, Jesper H; Ashraf, Haseem; Dirksen, Asger

2009-01-01

INTRODUCTION: Lung cancer screening with low dose computed tomography (CT) has not yet been evaluated in randomized clinical trials, although several are underway. METHODS: In The Danish Lung Cancer Screening Trial, 4104 smokers and previous smokers from 2004 to 2006 were randomized to either...... lung cancer. Ten of these had stage I disease. Eleven of 17 lung cancers at baseline were treated surgically, eight of these by video assisted thoracic surgery resection. CONCLUSIONS: Screening may facilitate minimal invasive treatment and can be performed with a relatively low rate of false......-positive screen results compared with previous studies on lung cancer screening....

High affective risk perception is associated with more lung cancer-specific distress in CT screening for lung cancer

NARCIS (Netherlands)

Bunge, Eveline M.; van den Bergh, Karien A. M.; Essink-Bot, Marie-Louise; van Klaveren, Rob J.; de Koning, Harry J.

2008-01-01

Screening for cancer can cause distress. People who perceive their risk of cancer as high may be more vulnerable to distress. This study evaluated whether participants of a lung cancer Computed Tomography (CT) screening trial with a high affective risk perception of developing lung cancer had a

Molecular pathways and therapeutic targets in lung cancer

Science.gov (United States)

Shtivelman, Emma; Hensing, Thomas; Simon, George R.; Dennis, Phillip A.; Otterson, Gregory A.; Bueno, Raphael; Salgia, Ravi

2014-01-01

Lung cancer is still the leading cause of cancer death worldwide. Both histologically and molecularly lung cancer is heterogeneous. This review summarizes the current knowledge of the pathways involved in the various types of lung cancer with an emphasis on the clinical implications of the increasing number of actionable molecular targets. It describes the major pathways and molecular alterations implicated in the development and progression of non-small cell lung cancer (adenocarcinoma and squamous cancer), and of small cell carcinoma, emphasizing the molecular alterations comprising the specific blueprints in each group. The approved and investigational targeted therapies as well as the immune therapies, and clinical trials exploring the variety of targeted approaches to treatment of lung cancer are the main focus of this review. PMID:24722523

Understanding Cancer Prognosis

Medline Plus

Full Text Available ... NCI NCI Overview History Contributing to Cancer Research Leadership Director's Page Deputy Director's Page Previous NCI Directors ... History of NCI Contributing to Cancer Research Senior Leadership Director Deputy Director Previous Directors NCI Organization Divisions, ...

Dilemmas in Lung Cancer Staging.

Science.gov (United States)

Vlahos, Ioannis

2018-05-01

The advent of the 8th edition of the lung cancer staging system reflects a further meticulous evidence-based advance in the stratification of the survival of patients with lung cancer. Although addressing many limitations of earlier staging systems, several limitations in staging remain. This article reviews from a radiological perspective the limitations of the current staging system, highlighting the process of TNM restructuring, the residual issues with regards to the assignment of T, N, M descriptors, and their associated stage groupings and how these dilemmas impact guidance of multidisciplinary teams taking care of patients with lung cancer. Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.

Multilevel Opportunities to Address Lung Cancer Stigma across the Cancer Control Continuum.

Science.gov (United States)

Hamann, Heidi A; Ver Hoeve, Elizabeth S; Carter-Harris, Lisa; Studts, Jamie L; Ostroff, Jamie S

2018-05-22

The public health imperative to reduce the burden of lung cancer has seen unprecedented progress in recent years. Realizing fully the advances in lung cancer treatment and control requires attention to potential barriers in their momentum and implementation. In this analysis, we present and evaluate the argument that stigma is a highly significant barrier to fulfilling the clinical promise of advanced care and reduced lung cancer burden. This evaluation of lung cancer stigma is based on a multilevel perspective that incorporates the individual, persons in their immediate environment, the healthcare system, and the larger societal structure which shapes perceptions and decisions. We also consider current interventions and interventional needs within and across aspects of the lung cancer continuum, including prevention, screening, diagnosis, treatment, and survivorship. Current evidence suggests that stigma detrimentally impacts psychosocial, communication, and behavioral outcomes over the entire lung cancer control continuum and across multiple levels. Interventional efforts to alleviate stigma in the context of lung cancer show promise, yet more work is needed to evaluate their impact. Understanding and addressing the multi-level role of stigma is a crucial area for future study in order to realize the full benefits offered by lung cancer prevention, control, and treatment. Coordinated, interdisciplinary, and well-conceptualized efforts have the potential to reduce the barrier of stigma in the context of lung cancer and facilitate demonstrable improvements in clinical care and quality of life. Copyright © 2018. Published by Elsevier Inc.

Exposure to secondhand tobacco smoke and lung cancer by histological type: a pooled analysis of the International Lung Cancer Consortium (ILCCO)

Science.gov (United States)

Kim, Claire H; Lee, Yuan-Chin Amy; Hung, Rayjean J; McNallan, Sheila R; Cote, Michele L; Lim, Wei-Yen; Chang, Shen-Chih; Kim, Jin Hee; Ugolini, Donatella; Chen, Ying; Liloglou, Triantafillos; Andrew, Angeline S; Onega, Tracy; Duell, Eric J; Field, John K; Lazarus, Philip; Le Marchand, Loic; Neri, Monica; Vineis, Paolo; Kiyohara, Chikako; Hong, Yun-Chul; Morgenstern, Hal; Matsuo, Keitaro; Tajima, Kazuo; Christiani, David C; McLaughlin, John R; Bencko, Vladimir; Holcatova, Ivana; Boffetta, Paolo; Brennan, Paul; Fabianova, Eleonora; Foretova, Lenka; Janout, Vladimir; Lissowska, Jolanta; Mates, Dana; Rudnai, Peter; Szeszenia-Dabrowska, Neonila; Mukeria, Anush; Zaridze, David; Seow, Adeline; Schwartz, Ann G; Yang, Ping; Zhang, Zuo-Feng

2014-01-01

While the association between exposure to secondhand smoke and lung cancer risk is well established, few studies with sufficient power have examined the association by histological type. In this study, we evaluated the secondhand smoke-lung cancer relationship by histological type based on pooled data from 18 case-control studies in the International Lung Cancer Consortium (ILCCO), including 2,504 cases and 7,276 controls who were never smokers and 10,184 cases and 7,176 controls who were ever smokers. We used multivariable logistic regression, adjusting for age, sex, race/ethnicity, smoking status, pack-years of smoking, and study. Among never smokers, the odds ratios (OR) comparing those ever exposed to secondhand smoke with those never exposed were 1.31 (95% CI: 1.17–1.45) for all histological types combined, 1.26 (95% CI: 1.10–1.44) for adenocarcinoma, 1.41 (95% CI: 0.99–1.99) for squamous cell carcinoma, 1.48 (95% CI: 0.89–2.45) for large cell lung cancer, and 3.09 (95% CI: 1.62–5.89) for small cell lung cancer. The estimated association with secondhand smoke exposure was greater for small cell lung cancer than for non-small cell lung cancers (OR=2.11, 95% CI: 1.11–4.04). This analysis is the largest to date investigating the relation between exposure to secondhand smoke and lung cancer. Our study provides more precise estimates of the impact of secondhand smoke on the major histological types of lung cancer, indicates the association with secondhand smoke is stronger for small cell lung cancer than for the other histological types, and suggests the importance of intervention against exposure to secondhand smoke in lung cancer prevention. PMID:24615328

Exposure to secondhand tobacco smoke and lung cancer by histological type: a pooled analysis of the International Lung Cancer Consortium (ILCCO).

Science.gov (United States)

Kim, Claire H; Lee, Yuan-Chin Amy; Hung, Rayjean J; McNallan, Sheila R; Cote, Michele L; Lim, Wei-Yen; Chang, Shen-Chih; Kim, Jin Hee; Ugolini, Donatella; Chen, Ying; Liloglou, Triantafillos; Andrew, Angeline S; Onega, Tracy; Duell, Eric J; Field, John K; Lazarus, Philip; Le Marchand, Loic; Neri, Monica; Vineis, Paolo; Kiyohara, Chikako; Hong, Yun-Chul; Morgenstern, Hal; Matsuo, Keitaro; Tajima, Kazuo; Christiani, David C; McLaughlin, John R; Bencko, Vladimir; Holcatova, Ivana; Boffetta, Paolo; Brennan, Paul; Fabianova, Eleonora; Foretova, Lenka; Janout, Vladimir; Lissowska, Jolanta; Mates, Dana; Rudnai, Peter; Szeszenia-Dabrowska, Neonila; Mukeria, Anush; Zaridze, David; Seow, Adeline; Schwartz, Ann G; Yang, Ping; Zhang, Zuo-Feng

2014-10-15

While the association between exposure to secondhand smoke and lung cancer risk is well established, few studies with sufficient power have examined the association by histological type. In this study, we evaluated the secondhand smoke-lung cancer relationship by histological type based on pooled data from 18 case-control studies in the International Lung Cancer Consortium (ILCCO), including 2,504 cases and 7,276 control who were never smokers and 10,184 cases and 7,176 controls who were ever smokers. We used multivariable logistic regression, adjusting for age, sex, race/ethnicity, smoking status, pack-years of smoking, and study. Among never smokers, the odds ratios (OR) comparing those ever exposed to secondhand smoke with those never exposed were 1.31 (95% CI: 1.17-1.45) for all histological types combined, 1.26 (95% CI: 1.10-1.44) for adenocarcinoma, 1.41 (95% CI: 0.99-1.99) for squamous cell carcinoma, 1.48 (95% CI: 0.89-2.45) for large cell lung cancer, and 3.09 (95% CI: 1.62-5.89) for small cell lung cancer. The estimated association with secondhand smoke exposure was greater for small cell lung cancer than for nonsmall cell lung cancers (OR=2.11, 95% CI: 1.11-4.04). This analysis is the largest to date investigating the relation between exposure to secondhand smoke and lung cancer. Our study provides more precise estimates of the impact of secondhand smoke on the major histological types of lung cancer, indicates the association with secondhand smoke is stronger for small cell lung cancer than for the other histological types, and suggests the importance of intervention against exposure to secondhand smoke in lung cancer prevention. © 2014 UICC.

NCI-FDA Interagency Oncology Task Force Workshop Provides Guidance for Analytical Validation of Protein-based Multiplex Assays | Office of Cancer Clinical Proteomics Research

Science.gov (United States)

An NCI-FDA Interagency Oncology Task Force (IOTF) Molecular Diagnostics Workshop was held on October 30, 2008 in Cambridge, MA, to discuss requirements for analytical validation of protein-based multiplex technologies in the context of its intended use. This workshop developed through NCI's Clinical Proteomic Technologies for Cancer initiative and the FDA focused on technology-specific analytical validation processes to be addressed prior to use in clinical settings. In making this workshop unique, a case study approach was used to discuss issues related to

Small Molecular TRAIL Inducer ONC201 Induces Death in Lung Cancer Cells: A Preclinical Study.

Science.gov (United States)

Feng, Yuan; Zhou, Jihong; Li, Zhanhua; Jiang, Ying; Zhou, Ying

2016-01-01

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) selectively targets cancer cells. The present preclinical study investigated the anti-cancer efficiency of ONC201, a first-in-class small molecule TRAIL inducer, in lung cancer cells. We showed that ONC201 was cytotoxic and anti-proliferative in both established (A549 and H460 lines) and primary human lung cancer cells. It was yet non-cytotoxic to normal lung epithelial cells. Further, ONC201 induced exogenous apoptosis activation in lung cancer cells, which was evidenced by TRAIL/death receptor-5 (DR5) induction and caspase-8 activation. The caspase-8 inhibitor or TRAIL/DR5 siRNA knockdown alleviated ONC201's cytotoxicity against lung cancer cells. Molecularly, ONC201 in-activated Akt-S6K1 and Erk signalings in lung cancer cells, causing Foxo3a nuclear translocation. For the in vivo studies, intraperitoneal injection of ONC201 at well-tolerated doses significantly inhibited xenografted A549 tumor growth in severe combined immunodeficient (SCID) mice. Further, ONC201 administration induced TRAIL/DR5 expression, yet inactivated Akt-S6K1 and Erk in tumor tissues. These results of the study demonstrates the potent anti-lung cancer activity by ONC201.

Small Molecular TRAIL Inducer ONC201 Induces Death in Lung Cancer Cells: A Preclinical Study.

Directory of Open Access Journals (Sweden)

Yuan Feng

Full Text Available Tumor necrosis factor (TNF-related apoptosis-inducing ligand (TRAIL selectively targets cancer cells. The present preclinical study investigated the anti-cancer efficiency of ONC201, a first-in-class small molecule TRAIL inducer, in lung cancer cells. We showed that ONC201 was cytotoxic and anti-proliferative in both established (A549 and H460 lines and primary human lung cancer cells. It was yet non-cytotoxic to normal lung epithelial cells. Further, ONC201 induced exogenous apoptosis activation in lung cancer cells, which was evidenced by TRAIL/death receptor-5 (DR5 induction and caspase-8 activation. The caspase-8 inhibitor or TRAIL/DR5 siRNA knockdown alleviated ONC201's cytotoxicity against lung cancer cells. Molecularly, ONC201 in-activated Akt-S6K1 and Erk signalings in lung cancer cells, causing Foxo3a nuclear translocation. For the in vivo studies, intraperitoneal injection of ONC201 at well-tolerated doses significantly inhibited xenografted A549 tumor growth in severe combined immunodeficient (SCID mice. Further, ONC201 administration induced TRAIL/DR5 expression, yet inactivated Akt-S6K1 and Erk in tumor tissues. These results of the study demonstrates the potent anti-lung cancer activity by ONC201.

Lung cancer in HIV Infection.

Science.gov (United States)

Mani, Deepthi; Haigentz, Missak; Aboulafia, David M

2012-01-01

Lung cancer is the most prevalent non-AIDS-defining malignancy in the highly active antiretroviral therapy era. Smoking plays a significant role in the development of HIV-associated lung cancer, but the cancer risk is two to four times greater in HIV-infected persons than in the general population, even after adjusting for smoking intensity and duration. Lung cancer is typically diagnosed a decade or more earlier among HIV-infected persons (mean age, 46 years) compared to those without HIV infection. Adenocarcinoma is the most common histological subtype, and the majority of patients are diagnosed with locally advanced or metastatic carcinoma. Because pulmonary infections are common among HIV-infected individuals, clinicians may not suspect lung cancer in this younger patient population. Surgery with curative intent remains the treatment of choice for early-stage disease. Although there is increasing experience in using radiation and chemotherapy for HIV-infected patients who do not have surgical options, there is a need for prospective studies because this population is frequently excluded from participating in cancer trials. Evidence-based treatments for smoking-cessation with demonstrated efficacy in the general population must be routinely incorporated into the care of HIV-positive smokers. Copyright © 2012 Elsevier Inc. All rights reserved.

Chapter 7: Description of miscan-lung, the erasmus mc lung cancer microsimulation model for evaluating cancer control interventions

NARCIS (Netherlands)

F.W. Schultz (Frank); R. Boer (Rob); H.J. de Koning (Harry)

2012-01-01

textabstractThe MISCAN-lung model was designed to simulate population trends in lung cancer (LC) for comprehensive surveillance of the disease, to relate past exposure to risk factors to (observed) LC incidence and mortality, and to estimate the impact of cancer-control interventions. MISCAN-lung

acetyltransferases: Influence on Lung Cancer Susceptibility

African Journals Online (AJOL)

Lung cancer remains a major health challenge in the world. It is the commonest cause of cancer mortality in men, it has been suggested that genetic susceptibility may contribute to the major risk factor, with increasing prevalence of smoking. Lung cancer has reached epidemic proportions in India. Recently indoor air ...

Angiogenin and vascular endothelial growth factor expression in lungs of lung cancer patients.

Science.gov (United States)

Rozman, Ales; Silar, Mira; Kosnik, Mitja

2012-12-01

BACKGROUND.: Lung cancer is the leading cause of cancer deaths. Angiogenesis is crucial process in cancer growth and progression. This prospective study evaluated expression of two central regulatory molecules: angiogenin and vascular endothelial growth factor (VEGF) in patients with lung cancer. PATIENTS AND METHODS.: Clinical data, blood samples and broncho-alveolar lavage (BAL) from 23 patients with primary lung carcinoma were collected. BAL fluid was taken from part of the lung with malignancy, and from corresponding healthy side of the lung. VEGF and angiogenin concentrations were analysed by an enzyme-linked immunosorbent assay. Dilution of bronchial secretions in the BAL fluid was calculated from urea concentration ratio between serum and BAL fluid. RESULTS.: We found no statistical correlation between angiogenin concentrations in serum and in bronchial secretions from both parts of the lung. VEGF concentrations were greater in bronchial secretions in the affected side of the lung than on healthy side. Both concentrations were greater than serum VEGF concentration. VEGF concentration in serum was in positive correlation with tumour size (p = 0,003) and with metastatic stage of disease (p = 0,041). There was correlation between VEGF and angiogenin concentrations in bronchial secretions from healthy side of the lung and between VEGF and angiogenin concentrations in bronchial secretions from part of the lung with malignancy. CONCLUSION.: Angiogenin and VEGF concentrations in systemic, background and local samples of patients with lung cancer are affected by different mechanisms. Pro-angiogenic activity of lung cancer has an important influence on the levels of angiogenin and VEGF.

Chemoradiotherapy for lung cancer. Current status and perspectives

International Nuclear Information System (INIS)

Ohe, Yuichiro

2004-01-01

For many years, thoracic radiotherapy had been regarded as the standard treatment for patients with unresectable locally advanced non-small cell lung cancer. However, meta-analyses show that cisplatin-containing chemoradiotherapy is significantly superior to radiotherapy alone in terms of survival. Moreover, concurrent chemoradiotherapy yields a significantly increased response rate and enhanced survival duration when compared with the sequential approach. Cisplatin-based chemotherapy with concurrent thoracic radiotherapy yields a 5-year survival rate of approximately 15% for patients with unresectable locally advanced non-small cell lung cancer. The state-of-the-art treatment for limited-stage small cell lung cancer is considered to be four cycles of combination chemotherapy with cisplatin plus etoposide combined with early concurrent twice-daily thoracic irradiation (45 Gy). If patients achieve complete remission, prophylactic cranial irradiation should be administered. A 5-year survival rate of approximately 25% is expected with the state-of-the-art treatment for limited-stage small cell lung cancer. Chemoradiotherapy is considered to be a standard treatment for both unresectable locally advanced non-small cell lung cancer and limited-stage small cell lung cancer. Several new strategies are currently being investigated to improve the survival of these patients. The incorporation of target-based drugs such as gefitinib is considered to be the most promising strategy for unresectable locally advanced non-small cell lung cancer. The incorporation of irinotecan is also a promising strategy to improve the survival of patients with limited-stage small cell lung cancer. The Japan Clinical Oncology Group is conducting clinical trials to develop new treatment strategies for both unresectable locally advanced non-small cell lung cancer and limited-stage small cell lung cancer. (author)

Inhalation treatment of lung cancer: the influence of composition, size and shape of nanocarriers on their lung accumulation and retention

International Nuclear Information System (INIS)

Garbuzenko, Olga B.; Mainelis, Gediminas; Taratula, Oleh; Minko, Tamara

2014-01-01

Various nanoparticles have been designed and tested in order to select optimal carriers for the inhalation delivery of anticancer drugs to the lungs. The following nanocarriers were studied: micelles, liposomes, mesoporous silica nanoparticles (MSNs), poly propyleneimine (PPI) dendrimer-siRNA complexes nanoparticles, quantum dots (QDs), and poly (ethylene glycol) polymers. All particles were characterized using the following methods: dynamic light scattering, zeta potential, atomic force microscopy, in vitro cyto- and genotoxicity. In vivo organ distribution of all nanoparticles, retention in the lungs, and anticancer effects of liposomes loaded with doxorubicin were examined in nude mice after the pulmonary or intravenous delivery. Significant differences in lung uptake were found after the inhalation delivery of lipid-based and non-lipid-based nanoparticles. The accumulation of liposomes and micelles in lungs remained relatively high even 24 h after inhalation when compared with MSNs, QDs, and PPI dendrimers. There were notable differences between nanoparticle accumulation in the lungs and other organs 1 and 3 h after inhalation or intravenous administrations, but 24 h after intravenous injection all nanoparticles were mainly accumulated in the liver, kidneys, and spleen. Inhalation delivery of doxorubicin by liposomes significantly enhanced its anticancer effect and prevented severe adverse side effects of the treatment in mice bearing the orthotopic model of lung cancer. The results of the study demonstrate that lipid-based nanocarriers had considerably higher accumulation and longer retention time in the lungs when compared with non-lipid-based carriers after the inhalation delivery. These particles are most suitable for effective inhalation treatment of lung cancer

Advances in combination therapy of lung cancer

DEFF Research Database (Denmark)

Wu, Lan; Leng, Donglei; Cun, Dongmei

2017-01-01

Lung cancer is a complex disease caused by a multitude of genetic and environmental factors. The progression of lung cancer involves dynamic changes in the genome and a complex network of interactions between cancer cells with multiple, distinct cell types that form tumors. Combination therapy......, including small molecule drugs and biopharmaceuticals, which make the optimization of dosing and administration schedule challenging. This article reviews the recent advances in the design and development of combinations of pharmaceuticals for the treatment of lung cancer. Focus is primarily on rationales...... for the selection of specific combination therapies for lung cancer treatment, and state of the art of delivery technologies and dosage regimens for the combinations, tested in preclinical and clinical trials....

Lung Cancer Survivorship

Centers for Disease Control (CDC) Podcasts

2016-10-20

A lung cancer survivor shares her story about diagnosis, treatment, and community support. She also gives advice for other cancer survivors.  Created: 10/20/2016 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 10/20/2016.

Missed lung cancer: when, where, and why?

Science.gov (United States)

del Ciello, Annemilia; Franchi, Paola; Contegiacomo, Andrea; Cicchetti, Giuseppe; Bonomo, Lorenzo; Larici, Anna Rita

2017-01-01

Missed lung cancer is a source of concern among radiologists and an important medicolegal challenge. In 90% of the cases, errors in diagnosis of lung cancer occur on chest radiographs. It may be challenging for radiologists to distinguish a lung lesion from bones, pulmonary vessels, mediastinal structures, and other complex anatomical structures on chest radiographs. Nevertheless, lung cancer can also be overlooked on computed tomography (CT) scans, regardless of the context, either if a clinical or radiologic suspect exists or for other reasons. Awareness of the possible causes of overlooking a pulmonary lesion can give radiologists a chance to reduce the occurrence of this eventuality. Various factors contribute to a misdiagnosis of lung cancer on chest radiographs and on CT, often very similar in nature to each other. Observer error is the most significant one and comprises scanning error, recognition error, decision-making error, and satisfaction of search. Tumor characteristics such as lesion size, conspicuity, and location are also crucial in this context. Even technical aspects can contribute to the probability of skipping lung cancer, including image quality and patient positioning and movement. Albeit it is hard to remove missed lung cancer completely, strategies to reduce observer error and methods to improve technique and automated detection may be valuable in reducing its likelihood. PMID:28206951

Epidemiological study on lung cancer of uranium miners

International Nuclear Information System (INIS)

Yuan Liyun; Gu Juanjuan

1994-01-01

Lung cancer among 13360 male workers of 5 uranium mines were investigated. During the period of observation (Jan, 1971-Dec. 1985) 35 lung cancers were registered; among them 24 were in exposed group and 11 in control group. Standard mortality of lung cancer for these two groups were 21.42·10 -5 and 15.94·10 -5 , respectively. SMR were 1.83 (exposed group) and 1.44 (control group) (P<0.01). The average latent period of lung cancer in exposed group was 17.5 years, and the average cumulative exposure dose to radon daughters was 168 WLM. The average age of workers dead of lung cancer was 47.83 years. The excess RR coefficient of lung cancer was 1.07%/WLM. SMR increased with increasing cumulative exposure dose to radon daughters. The adjusted mortality of long cancer of smokers in exposed group was obviously higher than that of nonsmokers

Using a chemiresistor-based alkane sensor to distinguish exhaled breaths of lung cancer patients from subjects with no lung cancer.

Science.gov (United States)

Tan, Jiunn-Liang; Yong, Zheng-Xin; Liam, Chong-Kin

2016-10-01

Breath alkanes are reported to be able to discriminate lung cancer patients from healthy people. A simple chemiresistor-based sensor was designed to respond to alkanes by a change in resistance measured by a digital multimeter connected to the sensor. In preclinical experiments, the sensor response was found to have a strong positive linear relationship with alkane compounds and not responsive to water. This study aimed to determine the ability of the alkane sensor to distinguish the exhaled breaths of lung cancer patients from that of chronic obstructive pulmonary disease (COPD) patients and control subjects without lung cancer. In this cross-sectional study, 12 treatment-naive patients with lung cancer, 12 ex- or current smokers with COPD and 13 never-smokers without lung disease were asked to exhale through a drinking straw into a prototype breath-in apparatus made from an empty 125 mL Vitagen ® bottle with the chemiresistor sensor attached at its inside bottom to measure the sensor peak output (percentage change of baseline resistance measured before exhalation to peak resistance) and the time taken for the baseline resistance to reach peak resistance. Analysis of multivariate variance and post-hoc Tukey test revealed that the peak output and the time to peak values for the lung cancer patients were statistically different from that for both the COPD patients and the controls without lung disease, Pillai's Trace =0.393, F=3.909, df = (4, 64), P=0.007. A 2.20% sensor peak output and a 90-s time to peak gave 83.3% sensitivity and 88% specificity in diagnosing lung cancer. Tobacco smoking did not affect the diagnostic accuracy of the sensor. The alkane sensor could discriminate patients with lung cancer from COPD patients and people without lung disease. Its potential utility as a simple, cheap and non-invasive test for early lung cancer detection needs further studies.

Lung Cancer in Renal Transplant Recipients

Directory of Open Access Journals (Sweden)

Jozicic Mirela

2016-06-01

Full Text Available Introduction. Although the incidence of malignancy has increased after solid organ transplantation, data on lung cancer in this group of patients is scarce. The aim of this study was to determine clinical characteristics and outcome of patients who developed lung cancer after renal transplantation. Methods. Among a cohort of 1658 patients who received a transplant at our institution and were followedup between 1973 and 2014, five patients developed lung cancer. We analyzed risk factors, transplantation characteristics, treatment options and survival. Results. Lung cancer was diagnosed in 5 patients (0.3%. Time to diagnosis after the transplant procedure ranged from 26 to 156 months (mean 115 months. All of them had a smoking history. Tumors were classified as IIB (20%, IIIA (40%, and IV (40%. Histological types included adenocarcinoma (80% and there was one case of sarcomatoid carcinoma (20%. One patient had concomitant thyroid papillary carcinoma. Radiotherapy was applied in 2 patients, 2 underwent chemotherapy (erlotinib and combination of carboplatinum and etopozide in one patient each, and 2 died within one month after the diagnosis from disseminated malignant disease. Patients with stage IIIA survived 14 and 24 months after the diagnosis. The patient with sarcomatoid cancer underwent thoracotomy with a complete resection, lost his graft function and died 7 months after the diagnosis. Conclusion. Lung cancer is relatively rare malignancy in renal transplant recipients, but associated with high mortality. Smoking is a significant risk factor, thus smoking cessation should be promoted among renal transplant recipients, as well as regular screening for lung cancer.

Health effects research and regulation of diesel exhaust: an historical overview focused on lung cancer risk.

Science.gov (United States)

Hesterberg, Thomas W; Long, Christopher M; Bunn, William B; Lapin, Charles A; McClellan, Roger O; Valberg, Peter A

2012-06-01

The mutagenicity of organic solvent extracts from diesel exhaust particulate (DEP), first noted more than 55 years ago, initiated an avalanche of diesel exhaust (DE) health effects research that now totals more than 6000 published studies. Despite an extensive body of results, scientific debate continues regarding the nature of the lung cancer risk posed by inhalation of occupational and environmental DE, with much of the debate focused on DEP. Decades of scientific scrutiny and increasingly stringent regulation have resulted in major advances in diesel engine technologies. The changed particulate matter (PM) emissions in "New Technology Diesel Exhaust (NTDE)" from today's modern low-emission, advanced-technology on-road heavy-duty diesel engines now resemble the PM emissions in contemporary gasoline engine exhaust (GEE) and compressed natural gas engine exhaust more than those in the "traditional diesel exhaust" (TDE) characteristic of older diesel engines. Even with the continued publication of epidemiologic analyses of TDE-exposed populations, this database remains characterized by findings of small increased lung cancer risks and inconsistent evidence of exposure-response trends, both within occupational cohorts and across occupational groups considered to have markedly different exposures (e.g. truckers versus railroad shopworkers versus underground miners). The recently published National Institute for Occupational Safety and Health (NIOSH)-National Cancer Institute (NCI) epidemiologic studies of miners provide some of the strongest findings to date regarding a DE-lung cancer association, but some inconsistent exposure-response findings and possible effects of bias and exposure misclassification raise questions regarding their interpretation. Laboratory animal studies are negative for lung tumors in all species, except for rats under lifetime TDE-exposure conditions with durations and concentrations that lead to "lung overload." The species specificity of the

Health effects research and regulation of diesel exhaust: an historical overview focused on lung cancer risk

Science.gov (United States)

Hesterberg, Thomas W.; Long, Christopher M.; Bunn, William B.; Lapin, Charles A.; McClellan, Roger O.; Valberg, Peter A.

2012-01-01

The mutagenicity of organic solvent extracts from diesel exhaust particulate (DEP), first noted more than 55 years ago, initiated an avalanche of diesel exhaust (DE) health effects research that now totals more than 6000 published studies. Despite an extensive body of results, scientific debate continues regarding the nature of the lung cancer risk posed by inhalation of occupational and environmental DE, with much of the debate focused on DEP. Decades of scientific scrutiny and increasingly stringent regulation have resulted in major advances in diesel engine technologies. The changed particulate matter (PM) emissions in “New Technology Diesel Exhaust (NTDE)” from today's modern low-emission, advanced-technology on-road heavy-duty diesel engines now resemble the PM emissions in contemporary gasoline engine exhaust (GEE) and compressed natural gas engine exhaust more than those in the “traditional diesel exhaust” (TDE) characteristic of older diesel engines. Even with the continued publication of epidemiologic analyses of TDE-exposed populations, this database remains characterized by findings of small increased lung cancer risks and inconsistent evidence of exposure-response trends, both within occupational cohorts and across occupational groups considered to have markedly different exposures (e.g. truckers versus railroad shopworkers versus underground miners). The recently published National Institute for Occupational Safety and Health (NIOSH)-National Cancer Institute (NCI) epidemiologic studies of miners provide some of the strongest findings to date regarding a DE-lung cancer association, but some inconsistent exposure-response findings and possible effects of bias and exposure misclassification raise questions regarding their interpretation. Laboratory animal studies are negative for lung tumors in all species, except for rats under lifetime TDE-exposure conditions with durations and concentrations that lead to'lung overload."The species specificity

Fludeoxyglucose F-18-PET in Planning Lung Cancer Radiation Therapy

Science.gov (United States)

2018-04-19

Stage I Lung Cancer; Stage I Non-Small Cell Lung Cancer AJCC v7; Stage IA Non-Small Cell Lung Carcinoma AJCC v7; Stage IB Non-Small Cell Lung Carcinoma AJCC v7; Stage II Lung Cancer; Stage II Non-Small Cell Lung Cancer AJCC v7; Stage IIA Non-Small Cell Lung Carcinoma AJCC v7; Stage IIB Non-Small Cell Lung Carcinoma AJCC v7

NCI Takes Back the Defelice Cup at Ninth Annual Golf Tournament | Poster

Science.gov (United States)

By Ashley DeVine, Staff Writer After being down by a point in the morning, NCI reclaimed the Defelice Cup trophy from Leidos Biomedical Research, with a final score of 12 ½ to 11 ½, at the ninth annual Ronald H. Defelice Golf Tournament, held Oct. 13. “The tightest matches in the nine-year history of this cup competition resulted in a narrow victory for NCI and allowed NCI to

Developing Cancer Informatics Applications and Tools Using the NCI Genomic Data Commons API.

Science.gov (United States)

Wilson, Shane; Fitzsimons, Michael; Ferguson, Martin; Heath, Allison; Jensen, Mark; Miller, Josh; Murphy, Mark W; Porter, James; Sahni, Himanso; Staudt, Louis; Tang, Yajing; Wang, Zhining; Yu, Christine; Zhang, Junjun; Ferretti, Vincent; Grossman, Robert L

2017-11-01

The NCI Genomic Data Commons (GDC) was launched in 2016 and makes available over 4 petabytes (PB) of cancer genomic and associated clinical data to the research community. This dataset continues to grow and currently includes over 14,500 patients. The GDC is an example of a biomedical data commons, which collocates biomedical data with storage and computing infrastructure and commonly used web services, software applications, and tools to create a secure, interoperable, and extensible resource for researchers. The GDC is (i) a data repository for downloading data that have been submitted to it, and also a system that (ii) applies a common set of bioinformatics pipelines to submitted data; (iii) reanalyzes existing data when new pipelines are developed; and (iv) allows users to build their own applications and systems that interoperate with the GDC using the GDC Application Programming Interface (API). We describe the GDC API and how it has been used both by the GDC itself and by third parties. Cancer Res; 77(21); e15-18. ©2017 AACR . ©2017 American Association for Cancer Research.

Estrogen Signaling in Lung Cancer: An Opportunity for Novel Therapy

International Nuclear Information System (INIS)

Baik, Christina S.; Eaton, Keith D.

2012-01-01

Lung cancer is the leading cause of cancer death in U.S. and represents a major public health burden. Epidemiologic data have suggested that lung cancer in women may possess different biological characteristics compared to men, as evidenced by a higher proportion of never-smokers among women with lung cancer. Emerging data indicate that female hormones such as estrogen and progesterone play a significant role in lung carcinogenesis. It has been reported that estrogen and progesterone receptors are expressed in lung cancer cell lines as well as in patient-derived tumors. Hormone related risk factors such as hormone replacement therapy have been implicated in lung carcinogenesis and several preclinical studies show activity of anti-estrogen therapy in lung cancer. In this review, we summarize the emerging evidence for the role of reproductive hormones in lung cancer and implications for lung cancer therapy

NCI Core Open House Shines Spotlight on Supportive Science and Basic Research | Poster

Science.gov (United States)

The lobby of Building 549 at NCI at Frederick bustled with activity for two hours on Tuesday, May 1, as several dozen scientists and staff gathered for the NCI Core Open House. The event aimed to encourage discussion and educate visitors about the capabilities of the cores, laboratories, and facilities that offer support to NCI’s Center for Cancer Research.

CT analysis of lung cancer and coexistent emphysema

International Nuclear Information System (INIS)

Noh, Kyung Hee; Chung, Myung Hee; Sung, Mi Sook; Yoo, Won Jong; Son, Kyung Myung; Son, Jung Min; Park, Seog Hee

2004-01-01

To evaluate the relation of the location and cell type of lung cancer to the location and degree in coexistent emphysema on high-resolution computed tomography (HRCT) scans. Ninety-eight of 209 lung cancer patients having HRCT scans were retrospectively analyzed to assess the total lung emphysema and peritumoral regional emphysema. Single and primary lung cancers were included. The clinical data, including sex, age, smoking history and the pathologic cancer subtype, were recorded to correlate with the HRCT findings. The lobar distribution, central-peripheral predominance, surrounding parenchymal abnormality for cancer, cephalocaudal predominance, and subtype for emphysema were analyzed on HRCT. Using a CT scoring method, we scored the whole lung emphysema and peritumoral emphysema, and correlated the grading of emphysema with pulmonary functional values. Sixty-nine of 98 patients with lung cancer (71%) had emphysema. Lung cancer with emphysema was significantly higher in men than in women, and was significantly related to smoking. The mean age of cancer patients without emphysema was significantly lower than that of cancer patients with emphysema (68 yrs vs. 61 yrs, p= 0.0006). Emphysema of grade I (0-25%) was found in 52 cases, grade II (25-50%) in 15, and grade III (50-75%) in 2. Total emphysema score was paralleled to peritumoral emphysema score in 64.3%, while the remaining patients had a higher peritumoral emphysema score (grade II or III) than total emphysema score (grade 0 or I). There was no statistical correlation in the developmental location between the emphysema and the lung cancer (significant correlation was only noted in grade II group of total emphysema score). The incidence of non-small cell carcinoma tended to be higher than that of small cell carcinoma in the two groups. The possibility of lung cancer in patients with pulmonary nodule, coexisting emphysema, and especially in elderly patients having a history of smoking must be clarified on HRCT

Inflammatory Gene Polymorphisms in Lung Cancer Susceptibility.

Science.gov (United States)

Eaton, Keith D; Romine, Perrin E; Goodman, Gary E; Thornquist, Mark D; Barnett, Matt J; Petersdorf, Effie W

2018-05-01

Chronic inflammation has been implicated in carcinogenesis, with increasing evidence of its role in lung cancer. We aimed to evaluate the role of genetic polymorphisms in inflammation-related genes in the risk for development of lung cancer. A nested case-control study design was used, and 625 cases and 625 well-matched controls were selected from participants in the β-Carotene and Retinol Efficacy Trial, which is a large, prospective lung cancer chemoprevention trial. The association between lung cancer incidence and survival and 23 polymorphisms descriptive of 11 inflammation-related genes (interferon gamma gene [IFNG], interleukin 10 gene [IL10], interleukin 1 alpha gene [IL1A], interleukin 1 beta gene [IL1B], interleukin 2 gene [IL2], interleukin 4 receptor gene [IL4R], interleukin 4 gene [IL4], interleukin 6 gene [IL6], prostaglandin-endoperoxide synthase 2 gene [PTGS2] (also known as COX2), transforming growth factor beta 1 gene [TGFB1], and tumor necrosis factor alpha gene [TNFA]) was evaluated. Of the 23 polymorphisms, two were associated with risk for lung cancer. Compared with individuals with the wild-type (CC) variant, individuals carrying the minor allele variants of the IL-1β-511C>T promoter polymorphism (rs16944) (CT and TT) had decreased odds of lung cancer (OR = 0.74, [95% confidence interval (CI): 0.58-0.94] and OR = 0.71 [95% CI: 0.50-1.01], respectively, p = 0.03). Similar results were observed for the IL-1β-1464 C>G promoter polymorphism (rs1143623), with presence of the minor variants CG and CC having decreased odds of lung cancer (OR = 0.75 [95% CI: 0.59-0.95] and OR = 0.69 [95% CI: 0.46-1.03], respectively, p = 0.03). Survival was not influenced by genotype. This study provides further evidence that IL1B promoter polymorphisms may modulate the risk for development of lung cancer. Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Smoking cessation and lung cancer screening

DEFF Research Database (Denmark)

Pedersen, Jesper Johannes Holst; Tønnesen, Philip; Ashraf, Haseem

2016-01-01

Smoking behavior may have a substantial influence on the overall effect of lung cancer screening. Non-randomized studies of smoking behavior during screening have indicated that computer tomography (CT) screening induces smoking cessation. Randomized studies have further elaborated that this effect...... and decrease smoking relapse rate. Also low smoking dependency and high motivation to quit smoking at baseline predicted smoking abstinence in screening trials. Lung cancer screening therefore seems to be a teachable moment for smoking cessation. Targeted smoking cessation counselling should be an integrated...... part of future lung cancer screening trials....

NCI and the Chinese Academy of Medical Sciences Sign Statement of Intent

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Today the National Cancer Institute (NCI) and the Cancer Institute/Hospital of the Chinese Academy of Medical Sciences (CICAMS) signed a statement of intent to share an interest in fostering collaborative biomedical research in oncology and a common goal