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J Trédaniel

Publications and source records attributed to J Trédaniel.

At least 37 records · Page 2Linked to original sources

[Genes and enzymes involved in the metabolism of carcinogens].

Most chemical carcinogens are not by themselves reactive. They are in fact procarcinogens and, before becoming toxic, they must undergo some metabolic transformations, directed by enzymatic systems under genetic control. Because of this system of defence, xenobiotics undergo in vivo a more or less sophisticated metabolic process that usually involved at least two phases: after activation phase (or "functionalization"), then a conjugation phase that allows elimination of the processed molecule. The initial step is in most cases on oxidation by P450 cytochroms. The conjugation step may involve a molecule of sulfate (sulfotransferase), of glucuronate (glucuronyltransferase) or of glutathione (glutathione-S-transferase). In man, large interindividual variations in the the expression in these enzymes have been demonstrated, probably depending on a genetic polymorphism. They are responsible for variations in individual susceptibility to carcinogens.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Do the nonsmoking daughters of smokers tend to marry smokers? Implications for epidemiological research on environmental tobacco smoke: the IARC collaborative study.

The IARC collaborative study on exposure to environmental tobacco smoke (ETS) involved collecting interview data and biochemical indicators of exposure from 1369 nonsmoking women in 13 centers in 10 countries. Information on childhood and adulthood exposure to other people's smoke and duration of this exposure from both parents and spouse was gathered at the interview. Of the 900 women whose husbands smoked (current or exsmokers), 71.3% had one or both parents who smoked (predominantly the father), whereas among the 277 women married to never-smokers, only 60.3% had at least one parent who smoked. The odds ratio for the daughter of a smoker to marry a smoker was, therefore, 1.64 (95% confidence interval = 1.24-2.17; P > 0.001), and there was an exposure-response relation between the number of years of childhood exposure to ETS from the parents and the likelihood of being married to a smoker. These results show that nonsmoking women married to smokers are more likely to have been exposed to tobacco pollution during their whole life. Because the duration of exposure is known to be important in the genesis of lung cancer, some of the excess risk of lung cancer in nonsmoking women married to smokers may be due exposure to ETS from parents during childhood.

Adolescent↗

Analyses of p53 antibodies in sera of patients with lung carcinoma define immunodominant regions in the p53 protein.

Antibodies specific for human p53 were analysed in sera of lung cancer patients. We detected p53 antibodies in the sera of 24% (10/42) of patients with lung carcinoma. The distribution was as follows: 4/9 small-cell lung carcinomas (SCLCs), 2/18 squamous cell lung carcinomas (SCCs), 2/10 adenocarcinomas (ADCs) and 2/5 large-cell lung carcinomas (LCCs). p53 antibodies were always present at the time of diagnosis and did not appear during progression of the disease. Using an original peptide-mapping procedure, we precisely localised the p53 epitopes recognised by p53 antibodies. Immunodominant epitopes reacting with antibodies were localised in the amino and carboxy termini of the protein, similar to those found in breast carcinoma patients or in animals immunised with p53. In light of these data, we suggest that p53 antibodies occur via a self-immunisation process that is the consequence of p53 accumulation in tumour cells. p53 antibodies were also detected in two patients without detected malignant disease. One of these patients died 6 months later of lung carcinoma, suggesting that p53 antibodies may be a precocious marker of p53 alteration.

Adenocarcinoma↗

Exposure to passive smoking during pregnancy and childhood, and cancer risk: the epidemiological evidence.

There are relatively few studies on the association between environmental tobacco smoke (ETS) during pregnancy and childhood, and cancer in childhood, adolescence or adulthood. The associations between maternal smoking during pregnancy and childhood cancer have been studied intensively, but there is no clear association overall, or for specific sites. The association between childhood cancer and smoking by the father in the preconceptional period, and by either parent during the child's lifetime, has been little studied. Again, no clear associations have been identified. However, evidence from studies of exposure to known carcinogens from ETS, and of genotoxic effects indicates that any effect, if present, is expected to be weak, and therefore could not have been detected by most of the studies which have been performed, due to the small number of cases included. There is some consistency of association between ETS exposure in childhood and the risk of lung cancers in adulthood. There is therefore a need for further epidemiological studies on ETS exposure during pregnancy and childhood and the occurrence of cancers.

Adolescent↗

Exposure to environmental tobacco smoke and adult non-neoplastic respiratory diseases.

Exposure to environmental tobacco smoke (ETS) is widespread in European countries, the most serious exposures occurring at home and in the workplace. Epidemiological studies have, essentially, addressed the association between ETS exposure and respiratory health in children, and increased risk of lung cancer among adult nonsmokers. Relatively few studies have been reported on ETS and adult non-neoplastic respiratory diseases. On the basis of the available data, no definite conclusion (excluding the acute irritating effect of ETS on respiratory mucous membranes) can be drawn. Although biologically plausible, it remains controversial whether ETS exposure is associated with chronic respiratory symptoms and occurrence of chronic obstructive pulmonary disease, including asthma. Most of the studies that have used the most sensitive indicators of pulmonary function have suggested a negative impact of ETS exposure. However, if really present, the physiological significance of such small changes is unclear, and the relationship to long-term changes in lung function is not established. Moreover, the possibility of bias and confounding factors must be taken into account. Thus, there is a need for further epidemiological studies on ETS exposure and adult non-neoplastic respiratory disorders.

Environmental Exposure↗

Endobronchial presentation of Hodgkin's disease: a report of nine cases and review of the literature.

Although mediastinal involvement by Hodgkin's disease is frequent, the initial presentation of the lymphoma by an endobronchial lesion is rare. Therefore, the question of whether patients with Hodgkin's disease should undergo fibreoptic bronchoscopy as a staging procedure remains unresolved. In a series of 469 patients with newly diagnosed Hodgkin's disease during a 10 year period, we reviewed the clinical features of nine patients who presented with an endobronchial tumour. They were compared to 34 previously published cases. The major presenting symptoms were cough, wheezing and haemoptysis. Bulky mediastinum was seen in six cases. The three other patients presented respiratory symptoms evocative of endoluminal invasion. All but one of the patients received combined modality therapy, as currently accepted for patients with poor prognostic factors. The overall actuarial survival was 74% after 4 yrs of follow-up. A selective subgroup of patients with stage I-II supradiaphragmatic and endobronchial Hodgkin's disease may, thus, present without poor prognostic factors (but generally with respiratory symptoms), and might be undertreated if this localization is not recognized. We propose that these patients should undergo fibreoptic bronchoscopy.

Adult↗

Exposure to environmental tobacco smoke and risk of lung cancer: the epidemiological evidence.

Exposure of nonsmokers to environmental tobacco smoke (ETS) is widespread in European countries, the most serious exposures occurring at home and in the workplace. Epidemiological studies available up to 1986 have been reviewed by several international and national authorities, which agreed in concluding that ETS exposure is causally related to lung cancer. A number of epidemiological studies have been published since then, and have confirmed this association. The possibility of positive results due to bias has been envisaged; it seems, however, that such bias could not explain the whole excess of lung cancer. Few data are available on confounders, such as diet and previous history of lung disease, that might be responsible for the association; however, there is no evidence that they play an important role. Moreover, the biological plausibility of a causal association is supported by the similarity of the composition of ETS and active smoke. The causal association between ETS exposure and lung cancer now seems well-established; however, its public health impact is still debated. Estimates are available from the United States, Canada, Australia, New Zealand and England.

Humans↗

Prolonged survival after high-dose rate endobronchial radiation for malignant airway obstruction.

STUDY OBJECTIVE: To show that prolonged survival can be observed after high-dose rate (HDR) endobronchial brachytherapy as the sole treatment for some selected patients presenting with an endobronchial malignant obstruction. PATIENTS: Twenty-nine patients (group 1) who presented with an endoluminal localized tumor without metastatic extension were treated by HDR endobronchial brachytherapy and are compared with 22 subjects who presented with extraluminal dissemination and were palliatively treated (group 2). TREATMENT PROTOCOL: Treatment consisted of sessions of two exposures, delivering 7 Grays at a 10-mm radius from the center of the applicator each, and repeated every 15 days, to a maximum of six exposures. Endoscopic response and survival are the main criteria of assessment. RESULTS: Follow-up bronchoscopies, performed 2 months after the end of the procedure, showed tumor regressions: macroscopic complete responses (CR) were observed in 21 of 25 patients evaluable in group 1, and 6 of 22 in group 2, with histologic CR in 18 and 2 patients, respectively. Median overall survival was not reached in group 1 after 23 months of follow-up; it was 5 months for group 2. CONCLUSIONS: These results confirm that HDR brachytherapy can be used as a monotherapy for carefully selected patients who have small tumors to all appearances limited to the bronchial lumen and bronchial wall without adjacent parenchymal extension or metastatic disease.

Airway Obstruction↗

[The p53 gene and protein in bronchial carcinogenesis:from biological to clinical aspects].

The p53 gene codes for a nuclear phosphoprotein which is capable of modulating the expression of certain genes implicated in the regulation of cell division. The mutation of an allele on the p53 gene with loss of the healthy allele, in different tissues such as lung, larynx, bladder, liver, skin, colon and breast, which may or may not be exposed to chemical or physical carcinogens (tobacco, radon, ultraviolet, aflatoxin B1), is associated with the occurrence of cancer. Indeed, the mutated p53 protein loses its anti-proliferative properties favouring a de-regulation of cellular multiplication with the accumulation of genetic aberrations. The homozygous deletion of the p53 gene in germ cells in the members of certain family cancers (Li-Fraumeni syndrome) leads to an increased incidence of cancers in the child or young adult. The most frequent mutations of the p53 gene end in a stabilisation of the mutated protein with immuno-histochemical nuclear marking of the cells carrying such an alteration. In certain patients this stabilisation of the mutated protein ends in auto-immunisation with anti-p53 serum antibodies. Bronchial cancer is a cancer of which the mutations of p53 are the most frequent (45-65% of bronchial cancer) as result of the mutagenic effect of tobacco smoke. These mutations seem to be associated with a bad prognosis and indeed to chemo-and radiotherapeutic resistance. The early diagnosis of p53 alterations (in dysplastic lesions or tumours which are only slightly developed) would enable new therapeutic interventions in bronchial cancer such as gene therapy or radio-immunotherapy to either restore the p53 gene to normality or to eliminate the cells expressing the mutated p53 protein respectively.

Alleles↗

Analysis of p53 antibodies in patients with various cancers define B-cell epitopes of human p53: distribution on primary structure and exposure on protein surface.

p53 antibodies have been found in sera of patients with breast and lung carcinomas and in children with B-lymphomas. We report here the presence of p53 antibodies in sera of patients with 11 different types of cancer. The frequency of seropositives for p53 varied among the different types of cancer, but a correlation with the frequency of p53 gene alteration was established. Using a powerful peptide enzyme-linked immunosorbent assay, we demonstrated that the immune response of patients with p53 antibodies was restricted to a small subset of peptides localized in the amino and carboxy termini of p53, whatever the type of cancer. Given the similarities of the patterns of immune responses in patients with p53 antibodies and animals hyperimmunized with human p53, we propose that the p53 humoral response is the result of a self-immunization process which is itself the consequence of p53 protein accumulation in tumor cells.

Amino Acid Sequence↗

[Passive smoking. Effects on health].

Passive smoking--also called involuntary or environmental smoking--is the exposure of non-smokers to the tobacco smoke released by smokers. The physico-chemical composition of tobacco smoke, and notably its contents in toxic and carcinogenic substances, is the same in the secondary stream between puffs as in the primary stream released by the smoker. The pathogenic effects of passive smoking are increasingly well known and accepted. A high incidence of respiratory tract infections and of chronic respiratory and asthmatic symptoms is observed in children. In adults, passive smoking seems to be one of the main risk factors for cardiovascular diseases. Its repercussions on the respiratory tracts is difficult to evaluate, but there are marked by an increase of respiratory symptoms and perhaps of chronic obstructive lung diseases. Finally, it is now recognized that passive smoking is a major risk factor for primary lung cancer in non-smokers exposed to tobacco smoke.

Adult↗

Environmental tobacco smoke and the risk of cancer in adults.

The apparent effect of environmental tobacco smoke (ETS) exposure on cancer risk has become an important social and political issue. The risk of cancer in non-smokers is often the main reason for prohibiting or restricting smoking in public places. A number of epidemiological studies have shown an association between ETS exposure and lung cancer. However, the strength of this association has still to be estimated. Only a few studies have reported on ETS and cancer from sites other than the lung in adults. No definite conclusions can be drawn at present from a critical review of the epidemiological evidence, but the suggestion of an association is present for sinonasal cancer, while bladder cancer does not seem to be associated to ETS exposure. Positive studies are available for cancers from other sites, including the breast, the uterine cervix and the brain, but these are difficult to interpret.

Adult↗

[High dose endobronchial curietherapy and its role in the relief of bronchial obstruction due to tumors].

The prognosis of tumours invading the lumen of the tracheobronchial tree is very poor. The majority of patients can only be offered symptomatic treatment. Different techniques to relieve bronchial obstruction have recently been developed. Amongst these is endobronchial radiation treatment at high dosage, with the advantage of enabling ambulatory treatment to be given with a satisfactory tolerance level. The treatment combines treatment both of the luminal invasion, but also of the component of the tumour which is extrinsic to the bronchi. Following a review of the literature, we have reviewed the technique, the indications and the results of this new method of treatment.

Airway Obstruction↗

[Smoking habits of French general practitioners. Results of a representative sample of 1,012 physicians].

General practitioners are in a position to influence the behaviour of the general population, notably as regards their smoking habits. This study aims to estimate the smoking habits of general practitioners in France, taken from a representative sample of 1012 general practitioners. The overall percentage of medical smokers rose in 1987 to 37%. The smoking habits varied according to age; thus if one considers current medical non-smokers, the oldest group are often ex-smokers, while the youngest are usually those who have never smoked. Compared to information obtained in 1980 from the medical population, one notes that there has been a fall in the level of doctors who smoke, whilst the proportion of doctors who have never smoked has risen considerably during the same period, particularly amongst young doctors.

Adult↗

[Granulo-monocyte growth factors. Their value in pneumonologic oncologic practice].

Granulo-monocytic growth factors are important members of the family of growth factors which alter the biological response. These factors are glycoproteins and are hormones regulating the production of haematopoietic cells and show their adaptation to possible needs. There are four which are currently well recognised; they are now grouped collectively under the term colony-stimulating factor and of these two, GM-CSF and G-CSF are available thanks to genetic engineering and have reached the stage of therapeutic trials. It is essentially the treatment of solid tumours which should lead to the most profound changes in the current management of cytotoxic drugs because they may allow an increase of the dose and a shortening of the duration of the phase of neutropenia and thus the infection risk. In therapeutic pneumonology they would be able to be used as an adjuvant to chemotherapy in small cell cancers and available in protocols using polychemotherapy with a risk of marrow suppression, indeed even permitting the practice of intensified chemotherapy regimes with or without the support of bone marrow graft. However the clinical experience acquired using growth factors remains limited and is almost exclusively restricted to the haematological domain. Although the secondary effects appear tolerable their harmlessness--and notably the absence of a stimulating effect on tumour growth--remains to be shown before extension of their use will lead to any changes of therapeutic strategies.

Antineoplastic Agents↗