Lung cancer diagnosed before it is detected by imaging

A team of researchers from Inserm led by Paul Hofman (Inserm Unit 1081/University of Nice) has just made a significant advance in the area of early diagnosis of invasive cancers. In a study which has just been published in the journal Plos One, the team shows that it is possible to detect, in patients at risk of developing lung cancer, early signs, in the form of circulating cancer cells, several months, and in some cases several years, before the cancer becomes detectable by CT scanning. This warning could play a key role in early surgical intervention, thereby making it possible to attempt the early eradication of the primary cancer site.

PhotoCP web cancer poumon

© Fotolia

Studies carried out in animals have clearly shown that invasive tumours shed cancer cells into the bloodstream from the very earliest stages of their formation, even before the tumours are detectable by diagnostic imaging. The possibility of identifying these “sentinel” cells is considered a major asset in the race against time for the early detection, and hence treatment, of cancer. Circulating cancer cells are extremely rare in the bloodstream, are very heterogeneous and fragile, and are difficult to isolate without bias or loss.

The team of researchers led by Paul Hofman used a blood test developed during French research[1], which isolates all types of tumour cells from the bloodstream, without any loss, leaving them intact. The team studied a group of 245 people without cancer, including 168 patients at risk of later developing lung cancer because they had Chronic Obstructive Pulmonary Disease (COPD). Participants systematically underwent the blood test and standard diagnostic imaging tests. Using the blood test, circulating cancer cells were identified in 5 patients (3%), whereas imaging did not show any nodules in the lungs.

In these 5 patients, a nodule became detectable 1-4 years after detection of circulating cancer cells by the blood test. They immediately underwent surgery, and analysis of the nodule confirmed the diagnosis of lung cancer. Monitoring of the patients for a minimum of one year after surgery showed no sign of recurrence in the 5 patients, leading one to hope that the cancer had been eradicated. At the same time, no nodules were detected during monitoring of subjects who did not have circulating cancer cells, and no cancer cells were detected in the bloodstream of “control” subjects without COPD.

Detection of these circulating cells via this blood test could play a key role in early surgical intervention, thus making it possible to aim for early eradication of the primary cancer site.

Lung cancer is one of the most lethal cancers. According to the American Cancer Society (ACS), one-year survival among these patients is 44%, and 5-year survival only 16%. Only 15% of these cancers are presently diagnosed at a stage where the disease is localised. Early detection could both improve patient survival and help to improve health economics. COPD is the 3rd leading cause of deaths in the USA, and is mainly caused by smoking.

[1] known as ISET (Isolation by SizE of Tumour cells), and developed by Rarecells Diagnostics.

October 29th 2014: World Stroke Day

Commonly referred to as a “stroke”, a Cerebrovascular Accident results from the interruption of blood flow to the brain. The deprivation of oxygen and essential nutrients causes brain cells to die, leading to permanent damage (speech or writing difficulty, memory problems, bodily paralysis to a greater or lesser extent), or even sudden death.

In France, CVA is the leading cause of acquired disability in adults and accounts for nearly 130,000 new cases every year.

World Cerebrovascular Accident Day is organised on 29 October each year and helps raise public awareness regarding the importance of immediate care for victims from onset of initial symptoms (confusion, speech problems, trouble understanding, dizziness, etc.).

Inserm researchers are also extremely active in this area and are striving to find new strategies for prevention, diagnosis and treatment.


A paralysed man walks again after a spinal cord operation

A paralysed man has been able to walk again after being treated by Polish surgeons at Wroclaw in south-west Poland. According to AFP, two years ago Darek Fidyka underwent two operations in Poland, performed by a team of doctors led by Dr Pawel Tabakow from Wrocław Medical University. This operation was the result of the researchers’ work, published in the journal Cell transplantation in 2013.

A BBC Panorama documentary reported on this medical first.

For a statement on this news item:

Pierre François Pradat, specialist spinal cord researcher in an Inserm unit and clinician at the Pitié-Salpétrière (AP-HP) hospital
Inserm Unit 1146 Biomedical Imaging Laboratory

Telephone number by request from the press service: rf.mresni@esserp

Ebola virus: update on research in France

The Ebola epidemic is continuing to spread, particularly in West Africa. According to the latest report by the World Health Organisation (WHO) dated 17 October, 9,216 cases of Ebola have been recorded and 4,555 people have died of the virus.

Laboratoire P4 Jean Mérieux/Inserm.


With the current situation of the Ebola epidemic, it quickly became necessary for French research to be mobilised rapidly.

In August 2014, the French Minister of Health and Secretary of State for Higher Education and Research made Aviesan responsible for preparing and organising the response of French research to infectious emergencies.

With extensive past experience and recognised for coordinating research during the H1N1 epidemic in 2009 and more recently in response to the emergence of the Chikungunya virus in the Caribbean in 2013, the Aviesan Institute of Microbiology and Infectious Disease benefitted from the expertise of the REACTing[1] network to launch the Ebola research programme.

This network relies on existing teams, research centres and platforms in France and southern countries.

The implementation of these projects is coordinated mainly by teams from Inserm, CEA, the Pasteur Institute, IRD, Universities, not forgetting a close partnership with teams in Guinea, Ivory Coast and Senegal. The network of ANRS sites and researchers in West Africa have also been mobilised.

The children from the Elfe cohort turn three and a half : first results from the first interviews

The Elfe1 children are now three and a half years old , and a new survey was launched on 21 October to gather more detailed information about early childhood. This survey was conducted for the first time by telephone and through home visits with the families. The success of this new stage comes from the investment made by all of the families who believe in the value of this research, which will continue until their child turns 20 years old. Led by INED and INSERM, and in partnership with EFS, this study requires many stages starting from data collection up until the researchers publish the results. Some of this data has just been published in the three fields of health, environment and social sciences.

Insight on the preliminary findings of the Elfe study, by Marie-Aline Charles,

Research director of Inserm Unit 1018 “Centre for Research in Epidemiology and Population Health”
Elfe study director (Ined-Inserm-EFS combined unit)

In the health field, the survey showed that 70 % of mothers breastfeed, a number that has significantly grown since the 1970’s2:

Although infant formula is a completely acceptable alternative today for mothers who do not want to or cannot breastfeed, a considerable amount of scientific research shows that breastfeeding has a positive effect on the health of the mother and child. The findings of this Elfe study confirm that there has been an increasing trend documented over the last several years to initiate breastfeeding in the maternity ward, in conjunction with numerous public health initiatives that were started to promote breastfeeding.

In the maternity ward, 59% of mothers breastfeed only and 11% give both a bottle and breast milk. Mothers who breastfeed more frequently are older, have a normal body weight and belong to a higher socio-professional category. Mothers born in other countries breastfeed more often; likewise for mothers who took childbirth education classes and who did not smoke during their pregnancy. It also appears that breastfeeding is more common when fathers are involved and present during the birth, and when couples are married.

To continue efforts to promote breastfeeding, researchers suggest involving fathers as much as possible while allowing more women to attend childbirth classes (for example, 70% of those in the working class did not attend a class, compared to 27% of those in the managerial/professional class).

In the field of environmental health, the preliminary findings on housing contamination by micro-organisms are going to be published3

3,000 dust collectors were placed in children’s rooms for the first two months of their life, and the micro-organisms collected (mites, mold, etc.) were analysed to evaluate their influence on future health, particularly respiratory health. Six different housing contamination profiles were identified, of which two were commonly found in Western France (one had high numbers of mites and bacteria, and the other had mites, bacteria and mold). A higher humidity rate and temperatures more conducive to the growth of these micro-organisms could explain these results. The geographic breakdown of these profiles overlaps with the breakdown from a recent study conducted in day care nurseries on the frequency of asthma in young children . The follow-up data from the Elfe children will help confirm whether or not there is a relationship between these contamination profiles and children’s respiratory health. The objective within the Elfe study is to observe the respiratory diseases in these regions more carefully in correlation with the quality of housing, ventilation, isolation, etc.

The next publications in the field of social sciences will provide information on how parents prepare for the birth of a child, and in particular their desire to find out the baby’s gender5

The Elfe results show that nearly nine future parents out of ten want to know the gender of their child before his/her birth. For their first child, 60% of parents have no preference. When they do have a preference, it is equal for mothers (20 % for a girl and 20% for a boy), while fathers favour boys (25% would prefer a boy and 14% a girl). When it is a second child, the proportion of parents who do not have a preference decreases slightly. And when they do have a preference, it depends greatly on the gender of the oldest child; parents often want mixed-gender siblings. One of this research project’s objectives is to measure if this preference influences the beginning of parenthood.

A new survey when the child is three and a half and entering preschool

Two contacts are planned during this important stage young children’s lives:

• A telephone interview with one of the parents will focus primarily on updating information about the child’s environment (family, social, economic, culture, diet, etc.), the parents’ child-rearing practices, the child’s psychomotor development and health events. New topics including entry into preschool will also be discussed.

• A home visit with approximately 10,000 families, which will provide direct contact with the child. Researchers will use drawing, visual games and image association to gather information about the child’s cognitive development and learning.
Vidéo ELFE enquêteur

Video – Survey home visit (French version)

For families who have already participated in the lab work component in the maternity ward, new non-invasive sample collections, such as a urine sample from the child, are scheduled. Dust will also be collected in a few households to measure the substances found in the children’s environment. Finally, volunteer families can have their child wear a “movement counter” or accelerometer to measure their physical activity and sleep quality.

The progress of this unprecedented study, which includes one child out of 50 of the births in France in 2011, is based on the involvement of families who agreed to an initial interview in the maternity ward and then regular follow-up. The Elfe study families are playing a vital role in research for 20 years!

About the Elfe study
The Elfe study involves a large number of French researchers in a wide variety of scientific disciplines. Led by the Institut National d’Etudes Démographiques (INED – French National Institute of Demographic Studies), the Institut National de la Santé et de la Recherche Médicale (INSERM – National Institute of Health and Medical Research), in partnership with the Etablissement Français du Sang (EFS French Blood Agency), the Elfe study is supported by the ministries in charge of research, sustainable development, social affairs and health, and by public institutions: Institut de Veille Sanitaire (InVS – Health Watch Institute), Caisse Nationale des Allocations Familiales (Cnaf – French national family allowances fund) and the Institut National de la Statistique et des Études Économiques (Insee – National Institute of Statistics and Economic Studies). The Elfe study receives aid from the State managed by the Agence Nationale de la Recherche [National Research Agency) under a program entitled “Investments of the Future” under reference ANR-11-EQPX-0038.

1 Elfe is the first French longitudinal study dedicated to monitoring children from birth to adulthood. It takes a look at childhood from the multiple perspectives of social science, health and environmental health in order to better understand the interaction between them. During four enrolment periods in 2011, more than 18,000 families agreed to take part in this Elfe adventure in metropolitan France.
2 BEH no. 27 from 07 October 2014, Prevalence of breastfeeding based on parent characteristics and delivery conditions. Results from the Elfe maternity survey, Metropolitan France, 2011, by Claire Kersuzan and coll., Institut national de la recherche agronomique (Inra – National Institute of Agronomic Research) (French version)
3 Steffi Rocchi, Gabriel Reboux and coll., Université de Franche Comté, UMR 6249 Chrono-environnement, publication to appear in Sciences of total Environment under the title: Microbiological characterization of 3193 French dwellings of Elfe cohort children.
4 Study conducted with 20,000 children in day care nurseries who presented with wheezing and asthma: Delmas MC, Prevalence and controlling asthma in young children, Revue des maladies respiratoires, 2012.
5 XVIIIe Aidelf international conference, Université de Bari, 26-30 May 2014, Olivia Samuel and coll., Université Versailles St Quentin, Spring/Ined-IPOPs

Human papillomavirus linked to auto-immune disease

Erosive oral lichen planus (OLP) is an auto-immune disease affecting skin and mucous membranes which results in an abnormal immune response against mucocutaneous cells. Today, scientists at the Institut Pasteur, Inserm, Paul Sabatier University (Toulouse) and the CNRS have proven that the immune cells involved in OLP are the same as those activated during an immune response to human papillomavirus (type HPV-16). This suggests a link between OLP and HPV. The results of this study were published in the Journal of Investigative Dermatology.

Erosive oral lichen planus (OLP) is an inflammatory disease which is considered auto-immune because of the abnormal immune response it triggers against other cells in the body. The condition affects mucous membranes around the mouth and genitals causing lesions and the destruction of skin cells called keratinocytes. Because current treatments are only partially effective, the condition is chronic and, although rare (between 0.1 and 4% of the overall population is affected), OLP can have serious side effects such as pain, difficulty eating, and cancer.


Papillomavirus© Institut Pasteur

Little was known about the underlying biological mechanisms of OLP until teams led by Marie-Lise Gougeon (Institut Pasteur), Nicolas Fazilleau (Inserm, Paul Sabatier University, CNRS) and Hervé Bachelez (Sorbonne Paris Cité, Paris Diderot University) demonstrated that the immune response which leads to the destruction of mucosal cells involves the same lymphocytes responsible for the immune response to human papillomavirus (HPV). This would suggest a link between OLP and infection by the HPV-16 strain, a virus known to be responsible for genital warts and cervical cancer.

Initial analyses of lesional tissue and blood samples from OLP patients revealed the presence of cytotoxic lymphocytes around the destroyed cells. This prompted scientists to try to characterize the specific role and origin of these lymphocytes.

For the ten patients enrolled in a study by Manuelle Viguier (Institut Pasteur, Sorbonne Paris Cité, Paris Diderot University), analyses showed an abnormally high population of a particular type of lymphocyte specific for HPV-16: T CD8 (type Vβ3).

The proportion of this type of lymphocyte was then measured during the different phases of OLP (outbreaks or remission stages). This allowed the scientists to show that the number of these cells decreased during periods of clinical remission and multiplied during outbreaks.

One of the theories put forward by the scientists was that keratinocytes in OLP patients might express an autoantigen (an endogenous normal tissue constituent) very similar to the HPV-16 antigen. This could be a source of confusion for T lymphocytes which, having already been exposed to HPV, might mistake the surface antigen on keratinocytes of OLP patients for the HPV antigen and trigger a cytotoxic immune response against keratinocytes.

This research indicates that the auto-immune disease OLP could involve T CD8 lymphocytes specific to HPV-16. This is the first time a link has been established between infection by HPV-16 and an auto-immune disease.

These results open up new therapeutic possibilities for treating severe forms of OLP. The Institut Pasteur has filed to patent this research in hopes that use of the HPV vaccine will be expanded to include OLP.

This study was financed by the French Dermatological Society, the Fondation ARC (Cancer Research Foundation), the French Cancer League, the French National Cancer Institute, the Midi-Pyrénées Regional Council and the Marie Curie International Re-integration Grant.


Key step in allergic reactions revealed

By studying the mode of action of the interleukin-33 protein, an alarmin for white blood cells, a team at the Institut de Pharmacologie et de Biologie Structurale (IPBS – CNRS/Université Toulouse III – Paul Sabatier) has been able to evidence truncated forms of the protein that act as potent activators of the cells responsible for triggering allergic reactions. This breakthrough in the understanding of the mechanisms underlying allergy could have important applications in the treatment of asthma and other allergic diseases such as eczema and allergic rhinitis. Co-directed by CNRS researcher Corinne Cayrol and INSERM senior researcher Jean-Philippe Girard, this work is published in PNAS on 13 October 2014.

Interleukin-33 (IL-33), discovered in 2003 by Jean-Philippe Girard’s team, is a protein in the family of interleukins, soluble messengers that enable communication between cells in the immune system and play a crucial role in tissue inflammation. This protein, which is stored in the blood vessels, lungs, skin or intestine, is only released in the event of cell damage. It acts as an alarmin that warns the body of trauma or infection by stimulating numerous cells in the immune system.

For several years, researchers have been trying to understand how the activity of interleukin-33 is regulated. They have now discovered that the protein is released by damaged cells and is then truncated by enzymes secreted by mastocytes, white blood cells that are key factors in allergy. By amplifying the danger signal to the immune system, these truncated forms have been shown to be 30 times more potent than the original form of interleukin-33.

The scientists have demonstrated that this highly potent signal is able to alert cells related to lymphocytes, group 2 innate lymphoid cells (ILC2). By triggering the chain reactions responsible for the allergic symptoms of asthma, eczema or allergic rhinitis, these cells have an essential role in allergy.

For the research team, preventing production of the truncated forms of interleukin-33 in order to reduce the allergic reactions triggered by ILC2 represents a promising strategy for the treatment of asthma and other allergic diseases.

This work notably received funding from the French National Research Agency (ANR), the Fondation ARC for cancer research and the French Medical Research Foundation (Fondation pour la Recherche Médicale – FRM)

Inserm launches Labo des Métiers (Career Lab): 3D immersion to discover careers in research

Inserm is launching the virtual Career Lab, in partnership with Sisso. This interactive tool, which is highly innovative and fun to use, is aimed at making young people aged 14-25 years aware of all the pieces that make up the great mosaic of scientific research.


screenshot –

Accessible right now via, from computers, tablets and smart phones, this virtual space enables those young adults who are tempted by jobs in research, but discouraged by the long studies they presume are involved, to discover the range of careers offered by the sector.

What is daily life like for a researcher? What are the studies that lead to such a career? What is the role of an engineer in a scientific project or the role of an assistant manager in a laboratory? Such are the questions that we try to answer via the virtual Career Lab,” explains Claire Lissalde, Manager of the audiovisual unit at Inserm’s Department of Scientific Information and Communication.

Visitors to the website are immersed in the heart of a laboratory, and a voiceover helps them to meet professionals working in biomedical research. An opportunity to learn about their career paths and shed light on careers that are often little understood, or considered beyond reach.

Thus Marie, an assistant in biological techniques, and Stéphanie, a researcher and joint manager of an Inserm team, Boris, manager of a phenotyping platform, Joanna, a technician in animal experimentation, Pablo, a post-doctoral fellow, and even Lila, secretary/manager of a research unit, will share their passion about their jobs with you.

Repeated episodes of depression: what are the effects on the brain?

Depression is not an ordinary case of the blues—it causes lasting changes to the intellectual functions unless it is managed. According to the results of a study carried out by Philip Gorwood (Inserm Unit 894, “Psychiatry and Neurosciences Center”, Mental and Brain illness Clinic – CMME, Saint Anne’s Hospital, Paris), people who have already experienced two or more depressive episodes perform routine cognitive tasks that require attention, concentration and speed abnormally slowly. These results, published in the journal European Neuropsychopharmacology, appear to confirm that depression may be a “neurotoxic” illness. Preventing recurrences is therefore clearly essential.



Depression is a common illness that has affected, affects or will affect at least one person out of ten. it is characterised by a permanent sadness, a loss of motivation and pleasure, and altered appetite, sleep and libido. Diagnosis corresponds to specific criteria established by international psychiatric standards. Although different types of management, based on drugs and psychotherapy, have been shown to be effective, the risk of recurrence is high, even after several years of remission.

The consequences of these repeated recurrences are a source of concern for physicians and researchers. Although it has already been proven that there is psychomotor retardation in depressed people (this is indeed one of the diagnostic criteria for the illness), there was until now no indication that this change could persist following a depressive episode.

To find out more, researchers at Inserm carried out a study in more than 2,000 patients who had experienced between 1 and over 5 depressive episodes during their lives. In order to assess their cognitive abilities, they measured the speed in performing a simple test (TMT: trail making test), which consists of linking numbered circles distributed in a disordered manner on a sheet of paper. The test was performed twice for each patient: during the depressive episode, and then 6 weeks later, by which time a good proportion of these patients were in complete remission (with no residual depressive symptoms).

Just after a first episode of depression, the time to perform this test was 35 seconds. These performances were almost identical among people undergoing the second depressive episodes in their lives. However, for people who had already had a history of 2, 3 or more depressive episodes, this time was considerably longer, even in subjects who had recovered (1 min 20 sec instead of 35 sec).

“Several other variables offer a potential explanation (age, education level, occupation, etc.), but if these parameters are adjusted, our results remain extremely robust,” explains Philip Gorwood.

Trails_Screenshot2 test TMA

Fig 1: Sample TMT    
Fig 2: Speed of performing TMT during and after depression, according to the number of depressive episodes previously experienced.

This result is the first to show in such a simple manner the “neurotoxic” effects of depression. It also supports the daily observations made by physicians, and the conclusions of earlier epidemiological studies indicating that depression is an illness that becomes worse with time. The researchers therefore judge that after treatment, prevention of recurrence must be one of the priorities for management.

Moreover, this study might also provide an explanation for this vicious circle: the more depressive episodes I have experienced, the more likely I am to have a recurrence. If speed and efficacy are increasingly altered with the number of recurrences, we imagine that it will become more difficult to adapt to new situations. For example, a worker at a computer, showing limited attention span, oversights in the tasks required, and general slowness in carrying out his/her work, will have lower self-esteem and less recognition from his/her work colleagues, which could make him/her more vulnerable to recurrences of his/her depression in the event of any stress.

Finally, the fact that these cognitive impairments may occur as a sequela of depression might also be considered as an argument in favour of the use of “cognitive remediation.” This therapy is based on the controlled stimulation of the impaired cognitive functions in order to reduce the risk of recurrence. It is widely used in schizophrenia and addiction, but is rarely used to treat depressive disorders.”

Inserm receives an honorable mention for the ‘Digital PR Award’ in the ‘Online Newsroom’ category for its press room

At a ceremony in New York, held on 10 October 2014, Inserm received one the four honorable mentions of the ‘Digital PR award’ for its bilingual online press room,, in the best ‘Online Newsroom’ category.

PR News’ Digital PR Awards is the industry’s top honor in the PR and communications digital space, recognizing outstanding digital initiatives among corporations, agencies and nonprofits. The winners of the Digital PR Awards are those organizations that took risks, made tremendous strides and understand the power of digital communications in public relations.

jh prix pr award

Juliette Hardy, Inserm press officer, attended the ceremony of the Digital PR Awards © Susan

The Inserm press room, launched by the press service in collaboration with Newround professionals at the beginning of 2013, was created to give journalists easier access to the results of work conducted by Inserm’s researchers. This digital initiative was set up to meet their needs for information and is adapted to changing practices in an environment where social media, in particular, are being continuously developed. The press room is viewed by an average 21,500 users per month (single visitors), in France and abroad, which is raising Inserm’s international profile.

The Inserm press service, part of Inserm’s Scientific Information and Communication Department (DISC), is honoured to see this honorable mention awarded to a French public institution. This contributes to rewarding the efforts made by Inserm to fulfil its role of bringing scientific information to a wide audience, particularly through the media.

About Inserm:

Created in 1964, the national institute for health and medical research (Inserm) is a public scientific and technological establishment, overseen jointly by the Ministry for Higher Education and Research and the Ministry of Health. The researchers aim to study all diseases, from the commonest to the rarest, through their work in biological and medical or population health research. Inserm is celebrating its 50th anniversary in 2014.

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On the PR Digital Award