Pulmonary Carcinoid Tumors and Asbestos Exposure

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Bénédicte Clin1,2,*, Pascal Andujar1,3,4, Issam Abd Al Samad5, Chantal Azpitarte6, FranÇoise Le Pimpec-Barthes7, Marie-Annick Billon-Galland8, Claire Danel9, FranÇoise Galateau-Salle10, Bruno Housset1,3,4, Karinne Legrand-Cattan11, Mireille Matrat1,3,4, Isabelle Monnet4, Marc Riquet7 and Jean-Claude Pairon1,3,4

1Institut National de la Santé et de la Recherche Médicale, U955, Equipe 4, Créteil 94000, France

2Service de Santé au Travail et Pathologie Professionnelle, Centre Hospitalier Universitaire de Caen, Caen 14000, France

3Faculté de Médecine, Université Paris Est, Créteil 94000, France

4Service de Pneumologie et de Pathologie Professionnelle, Centre Hospitalier Intercommunal de Créteil, Créteil 94000, France

5Service d’Anatomie Pathologique, Centre Hospitalier Intercommunal de Créteil, Créteil 94000, France

6Service de Santé au Travail, Société Nationale des Chemins de Fer Français, Paris 75010, France

7Service de Chirurgie Thoracique, Assistance Publique -Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris 75015, France

8Laboratoire d’Etude des Particules Inhalées de la Ville de Paris, Laboratoire d'Etude des Particules Inhalées de la Ville de Paris, Paris 75013, France

9Assistance Publique -Hôpitaux de Paris, Hôpital Bichat-Claude Bernard, Paris 75018, France

10Service d’Anatomie Pathologique, Centre Hospitalier Universitaire de Caen, Caen 14000, France

11Service de Santé au Travail, Pôle Santé Travail, Lille 59000, France ?* Author to whom correspondence should be addressed. Tel: +33-2-31-06-54-65; Fax: +33-2-31-06-49-14; e-mail: clin-b{at}chu-caen.fr Received November 10, 2011. Accepted February 14, 2012. Objectives: The hypothesis that asbestos exposure may have more specific associations with particular histological types of lung cancer remains controversial. The aim of this study was to analyze the relationships between asbestos exposure and pulmonary carcinoid tumors.

Methods: A retrospective case–control study was conducted in 28 cases undergoing surgery for pulmonary carcinoid tumors and aged >40 years and in 56 controls with lung cancer of a different histological type, matched for gender and age, from 1994 to 1999, recruited in two hospitals in the region of Paris. Asbestos exposure was assessed via expertise of a standardized occupational questionnaire and mineralogical analysis of lung tissue, with quantification of asbestos bodies (AB). Results: Definite asbestos exposure was identified in 25% of cases and 14% of controls (ns). Cumulative asbestos exposure was significantly higher in cases than in controls (P < 0.05), and results of the quantification of AB tended to be higher in cases than in controls (24 and 9% had >1000 AB per gram dry lung tissue, respectively, P = 0.09). Mean cumulative smoking was lower in cases than in controls (P < 0.05). Conclusions: This study argues in favor of a relationship between asbestos exposure and certain pulmonary carcinoid tumors. © The Author 2012. Published by Oxford University Press on behalf of the British Occupational Hygiene SocietyThis ArticleAnn Occup Hyg (2012) 56 (7): 789-795. doi: 10.1093/annhyg/mes017 First published online: May 4, 2012 PubMed citationArticles by Clin, B.Articles by Andujar, P.Articles by Abd Al Samad, I.Articles by Azpitarte, C.Articles by Le Pimpec-Barthes, F.Articles by Billon-Galland, M. A.Articles by Danel, C.Articles by Galateau-Salle, F.Articles by Housset, B.Articles by Legrand-Cattan, K.Articles by Matrat, M.Articles by Monnet, I.Articles by Riquet, M.Articles by Pairon, J. C.Current Issue
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Pulmonary Carcinoid Tumors and Asbestos Exposure

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Bénédicte Clin1,2,*, Pascal Andujar1,3,4, Issam Abd Al Samad5, Chantal Azpitarte6, FranÇoise Le Pimpec-Barthes7, Marie-Annick Billon-Galland8, Claire Danel9, FranÇoise Galateau-Salle10, Bruno Housset1,3,4, Karinne Legrand-Cattan11, Mireille Matrat1,3,4, Isabelle Monnet4, Marc Riquet7 and Jean-Claude Pairon1,3,4

1Institut National de la Santé et de la Recherche Médicale, U955, Equipe 4, Créteil 94000, France

2Service de Santé au Travail et Pathologie Professionnelle, Centre Hospitalier Universitaire de Caen, Caen 14000, France

3Faculté de Médecine, Université Paris Est, Créteil 94000, France

4Service de Pneumologie et de Pathologie Professionnelle, Centre Hospitalier Intercommunal de Créteil, Créteil 94000, France

5Service d’Anatomie Pathologique, Centre Hospitalier Intercommunal de Créteil, Créteil 94000, France

6Service de Santé au Travail, Société Nationale des Chemins de Fer Français, Paris 75010, France

7Service de Chirurgie Thoracique, Assistance Publique -Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris 75015, France

8Laboratoire d’Etude des Particules Inhalées de la Ville de Paris, Laboratoire d'Etude des Particules Inhalées de la Ville de Paris, Paris 75013, France

9Assistance Publique -Hôpitaux de Paris, Hôpital Bichat-Claude Bernard, Paris 75018, France

10Service d’Anatomie Pathologique, Centre Hospitalier Universitaire de Caen, Caen 14000, France

11Service de Santé au Travail, Pôle Santé Travail, Lille 59000, France ?* Author to whom correspondence should be addressed. Tel: +33-2-31-06-54-65; Fax: +33-2-31-06-49-14; e-mail: clin-b{at}chu-caen.fr Received November 10, 2011. Accepted February 14, 2012. Objectives: The hypothesis that asbestos exposure may have more specific associations with particular histological types of lung cancer remains controversial. The aim of this study was to analyze the relationships between asbestos exposure and pulmonary carcinoid tumors.

Methods: A retrospective case–control study was conducted in 28 cases undergoing surgery for pulmonary carcinoid tumors and aged >40 years and in 56 controls with lung cancer of a different histological type, matched for gender and age, from 1994 to 1999, recruited in two hospitals in the region of Paris. Asbestos exposure was assessed via expertise of a standardized occupational questionnaire and mineralogical analysis of lung tissue, with quantification of asbestos bodies (AB). Results: Definite asbestos exposure was identified in 25% of cases and 14% of controls (ns). Cumulative asbestos exposure was significantly higher in cases than in controls (P < 0.05), and results of the quantification of AB tended to be higher in cases than in controls (24 and 9% had >1000 AB per gram dry lung tissue, respectively, P = 0.09). Mean cumulative smoking was lower in cases than in controls (P < 0.05). Conclusions: This study argues in favor of a relationship between asbestos exposure and certain pulmonary carcinoid tumors. © The Author 2012. Published by Oxford University Press on behalf of the British Occupational Hygiene SocietyThis ArticleAnn Occup Hyg (2012) 56 (7): 789-795. doi: 10.1093/annhyg/mes017 First published online: May 4, 2012 PubMed citationArticles by Clin, B.Articles by Andujar, P.Articles by Abd Al Samad, I.Articles by Azpitarte, C.Articles by Le Pimpec-Barthes, F.Articles by Billon-Galland, M. A.Articles by Danel, C.Articles by Galateau-Salle, F.Articles by Housset, B.Articles by Legrand-Cattan, K.Articles by Matrat, M.Articles by Monnet, I.Articles by Riquet, M.Articles by Pairon, J. C.Current Issue
Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.

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Aggressive brain tumors can originate from a range of nervous system cells

ScienceDaily (Oct. 22, 2012) — Scientists have long believed that glioblastoma multiforme (GBM), the most aggressive type of primary brain tumor, begins in glial cells that make up supportive tissue in the brain or in neural stem cells. In a paper published October 17 in Science, however, researchers at the Salk Institute for Biological Studies have found that the tumors can originate from other types of differentiated cells in the nervous system, including cortical neurons.

GBM is one of the most devastating brain tumors that can affect humans. Despite progress in genetic analysis and classification, the prognosis of these tumors remains poor, with most patients dying within one to two years of diagnosis. The Salk researcher's findings offer an explanation for the recurrence of GBM following treatment and suggest potential new targets to treat these deadly brain tumors.

"One of the reasons for the lack of clinical advances in GBMs has been the insufficient understanding of the underlying mechanisms by which these tumors originate and progress," says Inder Verma, a professor in Salk's Laboratory of Genetics and the Irwin and Joan Jacobs Chair in Exemplary Life Science.

To better understand this process, Verma's team harnessed the power of modified viruses, called lentiviruses, to disable powerful tumor suppressor genes that regulate the growth of cells and inhibit the development of tumors. With these tumor suppressors deactivated, cancerous cells are given free rein to grow out of control.

To do that, Verma and his colleagues attached small RNA molecules, known as short hairpin RNAs, to the modified viruses and injected them directly into very few cells in the brains of genetically engineered mice that express an enzyme known as CRE specifically in neurons, astrocytes or neural stem cells. The modified viruses target two genes -- -neurofibromatosis 1 (NF1) and p53 -- -that, when mutated, are implicated in severe gliomas like GBM. Using sophisticated analytical techniques, they discovered that neurons genetically converted by the lentiviruses that also produce green fluorescent protein (GFP) as a marker to track the progression of tumors are capable of forming malignant gliomas.

Because the origin of glioblastomas from neurons has not been previously reported, the Salk scientists provided further evidence that mature neurons can be transformed by these oncogenes by isolating cortical neurons from genetically engineered mice and transducing them with one of the lentiviruses. The neurons that were transplanted back into the mice developed the same tumors as the ones in the laboratory.

"Our findings," says lead author Dinorah Friedmann-Morvinski, a postdoctoral researcher in the Laboratory of Genetics, "suggest that, when two critical genes -- -NF-1 and p53 -- -are disabled, mature, differentiated cells acquire the capacity to reprogram [dedifferentiate] to a neuroprogenitor cell-like state, which can not only maintain their plasticity, but also give rise to the variety of cells observed in malignant gliomas."

If scientists can block the process of dedifferentiation or proliferation of dedifferentiated neuroprogenitor cells, they may be able to stop tumor progression. That's important in an aggressive disease like GBM because of its high rate of recurrence.

"Our results offer an explanation of recurrence of gliomas following treatment," says Verma, "because any tumor cell that is not eradicated can continue to proliferate and induce tumor formation, thereby perpetuating the cycle of continuous cell replication to form malignant gliomas."

The scientists say the tumors in their mouse model are similar to GBMs that affect humans. Because they have the same pathology and characteristic genetic signature, scientists can study potential therapies in mice that should, theoretically, work in humans. While they may not eradicate GBM, these therapies may slow the progression of the disease and improve patients' quality of life.

Other researchers on the study were Eugene Ke, Yasushi Soda, Tomotoshi Marumoto and Oded Singer of the Salk Institute; and Eric Bushong and Mark Ellisman of the University of California, San Diego.

The work was supported by the National Institutes of Health, Ipsen/Biomeasure, the Leona M. and Harry B. Helmsley Charitable Trust, the H.N. and Frances C. Berger Foundation, and the National Center for Research Resources.

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The above story is reprinted from materials provided by Salk Institute for Biological Studies, via Newswise.

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Journal Reference:

D. Friedmann-Morvinski, E. A. Bushong, E. Ke, Y. Soda, T. Marumoto, O. Singer, M. H. Ellisman, I. M. Verma. Dedifferentiation of Neurons and Astrocytes by Oncogenes Can Induce Gliomas in Mice. Science, 2012; DOI: 10.1126/science.1226929

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Breakthrough technique images breast tumors in 3-D with great clarity, reduced radiation

ScienceDaily (Oct. 22, 2012) — Like cleaning the lenses of a foggy pair of glasses, scientists are now able to use a technique developed by UCLA researchers and their European colleagues to produce three-dimensional images of breast tissue that are two to three times sharper than those made using current CT scanners at hospitals. The technique also uses a lower dose of X-ray radiation than a mammogram.

These higher-quality images could allow breast tumors to be detected earlier and with much greater accuracy. One in eight women in the United States will be diagnosed with breast cancer during her lifetime.

The research is published the week of Oct. 22 in the early edition of the Proceedings of the National Academy of Sciences.

The most common breast cancer screening method used today is called dual-view digital mammography, but it isn't always successful in identifying tumors, said Jianwei (John) Miao, a UCLA professor of physics and astronomy and researcher with the California NanoSystems Institute at UCLA.

"While commonly used, the limitation is that it provides only two images of the breast tissue, which can explain why 10 to 20 percent of breast tumors are not detectable on mammograms," Miao said. "A three-dimensional view of the breast can be generated by a CT scan, but this is not frequently used clinically, as it requires a larger dose of radiation than a mammogram. It is very important to keep the dose low to prevent damage to this sensitive tissue during screening."

Recognizing these limitations, the scientists went in a new direction. In collaboration with the European Synchrotron Radiation Facility in France and Germany's Ludwig Maximilians University, Miao's international colleagues used a special detection method known as phase contrast tomography to X-ray a human breast from multiple angles.

They then applied equally sloped tomography, or EST -- a breakthrough computing algorithm developed by Miao's UCLA team that enables high-quality image-reconstruction -- to 512 of these images to produce 3-D images of the breast at a higher resolution than ever before. The process required less radiation than a mammogram.

In a blind evaluation, five independent radiologists from Ludwig Maximilians University ranked these images as having a higher sharpness, contrast and overall image quality than 3-D images of breast tissue created using other standard methods.

"Even small details of the breast tumor can be seen using this technique," said Maximilian Reiser, director of the radiology department at Ludwig Maximilians University, who contributed his medical expertise to the research.

The technology commonly used today for mammograms or imaging a patient's bones measures the difference in an X-ray's intensity before and after it passes through the body. But the phase contrast X-ray tomography used in this study measures the difference in the way an X-ray oscillates through normal tissue rather than through slightly denser tissue like a tumor or bone. While a very small breast tumor might not absorb many X-rays, the way it changes the oscillation of an X-ray can be quite large, Miao said. Phase contrast tomography captures this difference in oscillation, and each image made using this technique contributes to the overall 3-D picture.

The computational algorithm EST developed by Miao's UCLA team is a primary driver of this advance. Three-dimensional reconstructions, like the ones created in this research, are produced using sophisticated software and a powerful computer to combine many images into one 3-D image, much like various slices of an orange can be combined to form the whole. By rethinking the mathematic equations of the software in use today, Miao's group developed a more powerful algorithm that requires fewer "slices" to get a clearer overall 3-D picture.

"The technology used in mammogram screenings has been around for more than 100 years," said Paola Coan, a professor of X-ray imaging at Ludwig Maximilians University. "We want to see the difference between healthy tissue and the cancer using X-rays, and that difference can be very difficult to see, particularly in the breast, using standard techniques. The idea we used here was to combine phase contrast tomography with EST, and this combination is what gave us much higher quality 3-D images than ever before."

While this new technology is like a key in a lock, the door will only swing open -- bringing high-resolution 3-D imaging from the synchrotron facility to the clinic -- with further technological advances, said Alberto Bravin, managing physicist of the biomedical research laboratory at the European Synchrotron Radiation Facility. He added that the technology is still in the research phase and will not be available to patients for some time.

"A high-quality X-ray source is an absolute requirement for this technique," Bravin said. "While we can demonstrate the power of our technology, the X-ray source must come from a small enough device for it to become commonly used for breast cancer screening. Many research groups are actively working to develop this smaller X-ray source. Once this hurdle is cleared, our research is poised to make a big impact on society."

These results represent the collaborative efforts of senior authors Miao, Bravin and Coan. Significant contributions were provided by co-first authors Yunzhe Zhao, a recent UCLA doctoral graduate in Miao's laboratory, and Emmanuel Brun, a scientist working with Bravin and Coan. Other co-authors included Zhifeng Huang of UCLA and Aniko Sztrókay, Paul Claude Diemoz, Susanne Liebhardt, Alberto Mittone and Sergei Gasilov of Ludwig Maximilians University.

The research was funded by UC Discovery/Tomosoft Technologies; the National Institute of General Medical Sciences, a division of the National Institutes of Health; and the Deutsche Forschungsgemeinschaft-Cluster of Excellence Munich-Centre for Advanced Photonics.

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The above story is reprinted from materials provided by University of California - Los Angeles. The original article was written by Melody Pupols.

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Journal Reference:

Yunzhe Zhao, Emmanuel Brun, Paola Coan, Zhifeng Huang, Aniko Sztrókay, Paul Claude Diemoz, Susanne Liebhardt, Alberto Mittone, Sergei Gasilov, Jianwei Miao, and Alberto Bravin. High-resolution, low-dose phase contrast X-ray tomography for 3D diagnosis of human breast cancers. Proceedings of the National Academy of Sciences, 2012; DOI: 10.1073/pnas.1204460109

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Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

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