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M Tubiana

Publications and source records attributed to M Tubiana.

At least 37 records · Page 2Linked to original sources
PubMed1999

The link between local recurrence and distant metastases in human breast cancer.

PURPOSE: To distinguish between two possible explanations for the increased incidence of distant metastases observed in patients with locoregional recurrences (LR). Either LR is the signature of tumor aggressiveness, and avoiding recurrences (i.e., by radiotherapy) is of little value. The alternative is that LR is a nidus for metastatic dissemination. METHODS AND MATERIALS: Four thousand patients consecutively treated in the same institution from 1954 to 1975 were studied. None of them had received adjuvant chemotherapy. Tumor characteristics, local recurrence, and distant metastases had been prospectively registered. Duration of metastatic growth and probability of metastatic dissemination were estimated in the subsets of patients. RESULTS: The proportion of metastasis-free patients was reduced by about 80% in all subsets of patients with LR. In patients without LR, the monthly rate of distant metastases incidence decreases continuously with time after initial treatment. Conversely, in patients with local recurrence, this rate increases during the first year at initial treatment and the metastases in excess appear slightly later than in patients without local recurrence. Using a mathematical model, it can be shown that, in patients with local recurrence, nearly all of the metastases in excess had been initiated after initial treatment. The data also suggest that each year a small proportion of grade 1 residual tumors progresses toward a more malignant histologic type. CONCLUSIONS: Our results are not consistent with the hypothesis that a greater tumor aggressiveness in patients with LR could explain the excess of metastases. This conclusion is supported by the analysis of the delays between metastases' emergence, and death, which shows that tumors with or without LR have similar biological characteristics.

Adult↗
PubMed1999

The rationale for early diagnosis of cancer--the example of breast cancer.

The main advantage of early diagnosis of cancer is the reduction of tumor size at initial treatment and thereby an increase in the proportion of patients without distant dissemination. This benefit is illustrated by the example of breast cancer. A model of its natural history was built using data extracted from the files of over 4000 patients followed in the same institution for 20 to 35 years. The model was used to quantify the impact of tumor size, histologic grade, and lymph node involvement on the probability of distant spread. The relationships were found to be highly significant. The model also and unexpectedly revealed that the tumors progress while they grow; avoiding histologic progression is therefore another advantage of early diagnosis. The model showed that residual tumor can be a nidus for distant dissemination, and that consistency between the prediction of the model and the results of post-operative radiotherapy is satisfactory. Conversely to what is often stated, the benefits of post-operative radiotherapy appear to be greater for small tumors, even in the absence of lymph node involvement, than for large ones. The model could be used to help improve screening strategies, but more data are required, in particular for the young age range.

Brain Neoplasms↗
PubMed1999

Cancer prevention.

Over 70% of human cancers are associated with lifestyle and about half of cancer deaths could be prevented by relatively simple individual actions: no smoking, moderate consumption of alcohol, increased consumption of fruit and vegetables, avoidance of sunbathing, obesity and a too high consumption of saturated lipids. Most of these efforts would also markedly decrease the incidence of cardiovascular and respiratory diseases. However, the concept of prevention is currently neither well accepted nor understood by the medical community and the general public. It is often felt that it restricts freedom, imposes a choice between pleasure and duty, and that passing judgement on lifestyle is a form of intolerance. The case of tobacco illustrates the difficulties encountered by prevention, notably among adolescents. The fight against smoking requires information, a societal approach (ban on advertising, increase in price), and a reduction of the example given by adult smoking (parents, peers, teachers, physicians, TV presenters, movie stars, have a great influence on adolescents), while tobacco cessation programs must be promoted. The various approaches should be integrated into a global program of health prevention, including health education at school from 5 to 12 years of age. The efficacy of each of the global program's components should be evaluated. Misconceptions such as overestimation of the impact of pollution on health should also be corrected. Health is created and experienced by people within the setting of their daily lives, in particular during childhood. Prevention is the responsibility of individual members of the community but also of the community as a whole.

Adult↗
PubMed1998

Goralatide (AcSDKP), a negative growth regulator, protects the stem cell compartment during chemotherapy, enhancing the myelopoietic response to GM-CSF.

The aim of our study was to investigate the protection afforded to the bone marrow by Goralatide (AcSDKP), an inhibitor of hemopoietic stem cell proliferation, when administered alone or in combination with a growth factor (granulocyte/macrophage colony-stimulating factor [GM-CSF]) during iterative cycles of Ara-C (cytarabine) treatment. In control mice receiving the inhibitor alone without Ara-C, the number of granulocytes was reduced during treatment, and a surge in number of peripheral blood cells was observed after its completion. Peripheral hematological responses were monitored during 3 consecutive cycles of Ara-C chemotherapy and the resultant nadir and recoveries. Analysis of variance of the treatment effects pooled over the 3 cycles showed that a treatment regimen in which the inhibitor was administered during the myelotoxic periods of chemotherapy confirmed the existence of a surge after completion of administration of the inhibitor and showed a significant protective effect. When the cycles of chemotherapy plus Goralatide were followed by GM-CSF, the recovery from leukopenic nadirs was accelerated and the white blood cells and granulocyte levels were markedly increased over those observed in control mice and in mice treated either with Goralatide alone or with GM-CSF alone. The differences were highly significant. A consistent and significant increase (p < 0.001) in platelet count was also noted in animals given Goralatide in conjunction with Ara-C or Ara-C + GM-CSF. After three treatment cycles, this response to the CSF was far better in mice treated by the inhibitor than when CSF was given alone, suggesting a protection of the stem cell pool.

Animals↗
PubMed1998

The hazy dawn of brachytherapy.

The discovery of radium by Pierre and Marie Curie in December 1898 opened a new era in science and within a few years provided medicine with a new means of tumor treatment. Their personal contribution to the start and early development of clinical applications should not be overlooked. The Curies did not limit their support to providing radium sources to medical pioneers but took a deep interest in the horizons of radium therapy. Pierre was one of the first to search for and demonstrate a biological effect of radium radiation. He investigated the radioactivity of the waters of hydrotherapeutic resorts. Marie took care of the measurement of the medical sources personally, convinced that the result of the treatment depends on the precise knowledge of the amount of radium applied. Her perseverance resulted in the establishment of the Institut du Radium (1909) in which, besides the physico-chemical laboratory, a biological department was set up. The latter became the Fondation Curie (1920), a leading medical center of treatment and training, with an integrated team of physicists, radiobiologists and clinicians led by Regaud. One hundred years after the discovery of radium, patients benefit today from the extensive clinical experience that has been collected over the years and from sophisticated developments in application techniques, dosimetry and quality assurance; the professional risk has been precisely assessed and the improvements in material and procedure have enabled the medical personnel to work in hazard-free conditions. This outcome results from the continuous progress that the pioneers gave impulse to. This paper intends to recall their efforts and achievements, as well as the difficulties and the problems they encountered during the first 2 decades when the sturdy foundations of brachytherapy were built.

Animals↗
PubMed1998

The report of the French Academy of Science: 'Problems associated with the effects of low doses of ionising radiation'.

In 1995 the French Academy of Science published a report on 'Problems associated with low doses of ionising radiation'. This report aroused interest among French-speaking scientists and a translation in English was published a year later. The report pointed out that an important issue in radioprotection was not whether to accept or reject the linear no-threshold model but rather to test its validity. The aim of this review is to analyse the report and its recommendations, and to briefly indicate the progress which has been made and the questions which remain open. Three areas of the report are covered in this review: DNA repair, carcinogenesis and epidemiological data.

Animals↗
PubMed1998

[Benefits and limitations of mass screening. The natural history of breast cancer].

Most mortalities caused by breast cancers are due to metastases. A breast cancer gives rise to lymphatic spread, which is at the origin of nodal involvement, and to distant dissemination, usually through the bloodstream. Nodal involvement, which generally occurs before metastatic dissemination, appears not to be the cause of the dissemination but rather an index of the likelihood of a tumor to metastasize. This likelihood is influenced by the histological grade and the growth rate of the tumor. Despite the variations in biological characteristics of breast tumors and the likelihood of metastatic dissemination, the existence of a relationship between tumor size and the probability of metastatic dissemination enables the calculation of how many disseminations could be avoided through early diagnosis and thus the gain in human life that screening could hope to achieve. However, in reality, the effective gain is lesser because the rate of participation is lower than 100% and the existence of false negatives (undetected cancers) reduces the number of detected cancers. Furthermore, a high rate of false positives increases the anxiety of women because they provoke unnecessary examinations. Screening is worthwhile only if the increase in human life outweighs the economic and social costs (anxiety, going to appointments) that it may produce. It is therefore necessary to improve the benefits (fewer false negatives) and to decrease the social and psychological costs (fewer false positives). This can be done by the implementation of rigorous quality assurance, systematic training of health care personnel, a follow-up of women who have been screened, and an annual assessment of screening results. Screening in France since 1994 has shown a marked improvement since the implementation of guidelines prepared by the national screening committee which emphasize the need for quality control and ongoing training of staff. However, the results vary greatly from one county to another and are often below European standards, although some regions in France are close to achieving these. This shows that the system of screening in France, despite its organization involving many private and public radiology departments, can give results equal to those in countries in which screening is performed by a small number of specialized units. The French system requires regional structures of orientation and evaluation. To be effective, these structures must be guided by written legislation and regulations, otherwise they will be unable to overcome the difficulties currently faced by the implementation of mass screening.

Adult↗
PubMed1998

[Carcinogenesis: from epidemiology to molecular biology].

Carcinogenesis is a multi-step process and at least three stages can be distinguished: initiation, promotion and progression. Initiation is made up of events whereby an exogenous or endogenous carcinogen induces alterations in the genome of the cell; this results in a lesion that can be inherited and which confers upon that cell the potential for neoplastic growth. This is the result of activation of cellular proto-oncogenes into transforming oncogenes and/or the inactivation of the two alleles of tumor suppressor genes (anti-oncogenes). Although it is conceivable that a single event or a single lesion can initiate a cell it is probable that in most cases initiation is the consequence of a series of events since the different types of proto-oncogenes do not function independently of each other. The coordinated activation of more than one oncogene is generally required to confer the full potential for neoplastic growth. DNA repair and apoptosis play a critical role in carcinogenesis and the effectiveness of these mechanisms might be influenced by the dose and the time interval between individual events (dose rate). Epidemiological and experimental data show also the main role of cell proliferation after initiation. Proliferation influences the probability of DNA repair and contributes to further genomic alteration. Cell to cell interaction within a tissue participates in the control of cell proliferation and cell repair. The evolution of one initiated cell is not independent of the surrounding cells and disorganization of a tissue is a factor in carcinogenesis. Presently carcinogenesis appears to be a complex phenomenon which cannot be a adequately modelled. The linear no-threshold model has been used for the purpose of cancer prevention and legal norms, however it should be realized that its experimental and theoretical bases are debatable and that much recent data do not support them. Its predictions should therefore be considered with great caution. All efforts should be made in the future to build new models incorporating available epidemiological and fundamental data.

Carcinogens↗
PubMed1997

From Bertha Roentgen's hand to current medical imaging: one century of radiological progress.

From 1896 to 1996 radiology progressed at an amazing and unforeseen pace. The analysis of a few examples shows that these developments were due to a few groups and were enhanced by a close interaction between radiologists, physicists, engineers and manufacturers. Radiologists emphasize needs and are often able to suggest avenues for research; engineers exploit the basic discoveries of physicists and find new technologies. Manufacturers proceed from prototypes to instruments that can be built on an industrial scale at an affordable price. This system works efficiently only in a few developed countries. The gap between developing and developed countries is not narrowing and a large proportion of the world population has no access to adequate medical imaging. Very sophisticated imaging technologies used in industrialized countries are costly in terms of both money and human resources and in developing countries may usurp the limited assets that are needed for public health. Thus, the current challenge facing radiology is to take advantage of technological progress, firstly for building affordable and easy to maintain equipment giving images of sufficient quality, and secondly, through progress in telecommunications and computers, to improve medical education, telemedicine and build hospital networks. These networks will enable easier access to consultations with specialized radiologists and will give physicians the means of sharing their medical expertise. The aim is not only to narrow the gap but to provide a sufficient level of care in imaging medicine and radiotherapy throughout the world. This will only be achieved through a clear strategy and adequate human, technical and financial resources. The role of the radiological community, in particular ISR, RSNA and EAR, shall be crucial in this endeavour.

Developing Countries↗
PubMed1996

Hodgkin's disease: historical perspective and clinical presentation.

In conclusion, emphasis has shifted from a progressive increase in the weight of treatment to the reduction of management aggressiveness for some subsets of patients by taking advantage of clinical presentation and risk factors. The first period was based on the philosophy that extensive work-up can help to minimize treatment. The goal has become to avoid unnecessary invasive techniques. With better knowledge of the late effects and causes of death, there is now a consensus that management should be modulated according to the individual characteristics of the patient. The aim of further studies will be to progress in the identification of the various subsets of HD and to introduce new therapeutic modalities as effective but less toxic than the present ones. This approach requires for each subset of patients a rigorous assessment of the long-term cost and benefit of the various therapeutic modalities used for treatment of HD.

History, 19th Century↗
PubMed1996

[Wilhelm Conrad Röntgen and the discovery of X-rays].

W.C. Röntgen reported the discovery of X-rays in December 1895 after seven weeks of assiduous work during which he had studied the properties of this new type of radiation able to go through screens of notable thickness. He named them X-rays to underline the fact that their nature was unknown. The news of this discovery immediately aroused an immense interest in the public and also initiated intense research in several directions. Physicians and physicists began as early as January 1896 to use X-rays on patients to investigate the skeleton and subsequently the lung and other organs. This was the birth or radiology. Rapidly they observed skin erythema, which led to the idea of using X-rays against a variety of lesions. In June 1896 the first patient was treated by radiotherapy. J.J. Thomson (Cambridge, U.K.) showed that X-rays were able to ionize gaz and the study of this phenomenon led to the discovery of electrons in 1897. In order to understand the emission of X-rays, H. Becquerel (Paris) investigated the role of the phosphorescence of the glass of the tube and while doing so discovered radioactivity in March 1896. X-rays and radioactivity were at the origin of the scientific revolution at the end of the 19th and the beginning of the 20th centuries. Research on radioactive materials demonstrated the existence of atoms which had been till then only a convenient hypothesis for explaining chemical reactions, but whose reality was considered as dubious by most physicists. Moreover, interaction of particles emitted by radionuclides and atoms enabled first the study of the structure of the atom and subsequently its nucleus. Matter, elements which were thought to be immutable were found to be transmutable, and eventually to disintegrate. The origin of the energy transferred to the radiation which was emitted appeared as a mystery and in order to explain it the physicist had to accept that matter could convert energy. In 1903 Einstein established the equivalence between matter and energy. Matter, energy, electricity, light which were formerly considered as continuous quantities were found to be discrete: there are particles of matter (elementary particles), energy (quanta, Planck 1905), electricity (electron), light (photons). Radioactive decay, particle interactions imposed a probabilistic physics which progressively replaced classic deterministic physics. Radioactivity can be used as a clock to measure time in the universe. Datations were made for fossils, art masterpieces and also for the earth, the solar system and universe. X-rays diffraction proved to be a powerful tool for studying crystals and molecules, in particular protein, and in 1953 enabled to demonstrate the DNA double helix. Hence X-rays and radioactivity originated a revolution in physics and science and in the vision of nature. The imperceptible and yet so powerful rays demonstrated the deficiencies of our senses. Mathematical entities and instrumentation must complement our sensations. The huge increment in our knowledge is accompanied by a divorce between the scientist and the layman who now often has great difficulties understanding new concepts not only in physics but also in biology.

Germany↗