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Biomedical subjects

G Zalcman

Publications and source records attributed to G Zalcman.

At least 37 records · Page 2Linked to original sources
PubMed1997

[Intrabronchial curietherapy. Experiences at Hôpital Saint-Louis after the treatment of 149 patients].

Endobronchial tumour obstruction threatens to occur in cases of carcinoma of the bronchus throughout the course of the disease. Such patients can benefit from relief of the bronchial obstruction by several techniques which are currently available. We have treated 149 patients with endobronchial radiotherapy. Seventy three patients were treated with a view to cure, 47 with a palliative dose and 29 received endobronchial radiation in complement with external irradiation. The treatment was carried out in series repeated every 15 days until a maximum of three treatments, consisting of two sessions at 24 hour intervals delivering at each session and irradiating of 7 Gy with a 1 cm catheter. All the clinical signs were relieved and in 79% of patients there was a symptomatic benefit. One hundred and thirty two patients were evaluated by control endoscopy two months after the treatment and 64 had a complete histological remission. The median survival was 14.4 months for patients treated with intent to cure. Obtaining a histological remission was a gauge for prolonged survival (median survival 26.5 months), 11 (7.4%) had massive hemoptysis and 13 (8%) irradiation pneumonitis, all of which occurred some time after the therapeutic procedure. The results confirm the feasibility and the good results of endobronchial irradiation in this field and encourage the idea of controlled multi-centre trials in order to assess a placed of endobronchial radiotherapy in the therapeutic strategy of bronchial cancer.

Adenocarcinoma↗
PubMed1996

RhoGDI-3 is a new GDP dissociation inhibitor (GDI). Identification of a non-cytosolic GDI protein interacting with the small GTP-binding proteins RhoB and RhoG.

RhoB is a small GTP-binding protein highly homologous to the RhoA protein. While RhoA is known to regulate the assembly of focal adhesions and stress fibers in response to growth factors, the function of RhoB remains unknown. We have reported that the transient expression of the endogenous RhoB protein is regulated during the cell cycle, contrasting with the permanent RhoA protein expression (). Using the yeast two-hybrid system to characterize proteins interacting with RhoB, we identified a new mouse Rho GDP dissociation inhibitor, referenced as RhoGDI-3. The NH2-terminal alpha helix of RhoGDI-3 is strongly amphipatic and differs thus from that found in previously described bovine, human, and yeast RhoGDI proteins and mouse and human D4/Ly-GDIs. Contrary to the cytosolic localization of all known GDI proteins, acting on Rab or Rho, RhoGDI-3 is associated to a Triton X-100-insoluble membranous or cytoskeletal subcellular fraction. In the two-hybrid system, RhoGDI-3 interacts specifically with GDP- and GTP-bound forms of post-translationally processed RhoB and RhoG proteins, both of which show a growth-regulated expression in mammalian cells. No interaction is found with RhoA, RhoC, or Rac1 proteins. We show that GDI-3 is able to inhibit GDP/GTP exchange of RhoB and to release GDP-bound but not GTP-bound RhoB from cell membranes.

Amino Acid Sequence↗
PubMed1996

Fluoxetin-induced pulmonary granulomatosis.

A patient treated with fluoxetin for a manic depressive disorder developed pulmonary inflammatory nodules with noncaseating giant cell granulomas, interstitial pneumonia and non-necrotizing vasculitis, whilst remaining asymptomatic. A progressive resolution of pulmonary nodules occurred after withdrawal of the offending agent, and the chest radiograph returned to normal in 9 months. The diagnosis was assessed by an open lung biopsy.

Antidepressive Agents, Second-Generation↗
PubMed1995

Regulation of Ras-related RhoB protein expression during the cell cycle.

The immediate-early gene rhoB codes for a small GTP-binding protein highly homologous to the RhoA protein. While RhoA is known to regulate the assembly of focal adhesions and stress fibers in response to growth factors, the function of RhoB remains unknown. In a first attempt to elucidate its function, we examined the variation of the RhoB protein expression in response to induction of its mRNA. We report here that RhoB is an unstable protein rapidly and transiently induced by growth factors in PC12 and HeLa cells. Moreover, RhoB protein accumulation is periodic through the cell cycle. First detected at the G1/S phase transition, the level of the RhoB protein is maximal during the S phase and declines at the S/G2-M transition. This timing suggests that RhoB plays a role in the G1/S phase transition and/or in the S phase of the cell cycle. We also confirm here a vesicular and perinuclear localization of the endogenous RhoB protein induced by growth factors.

Cell Cycle↗
PubMed1995

Serum p53 antibodies as early markers of lung cancer.

The p53 alteration is the most common alteration found in human cancer. It usually involves missense mutations that stabilize the p53 protein, which in turn accumulates, reaching levels detectable by immunohistochemistry. We and others have demonstrated that this overexpression of mutant p53 protein can induce a specific humoral response in cancer patients. This result was assessed by the presence of p53 antibodies in sera of patients with various types of cancers, whereas normal populations do not exhibit such antibodies. In lung cancer, the prevalence of p53 antibodies is high (30%) and is correlated with a very high rate of p53 mutations in this cancer (60-70%). We show that these antibodies are always present at the time of diagnosis, but never appear during tumour development, an observation strengthened by the fact that these antibodies are mostly IgG, corresponding to a secondary immune response. These results suggest that the humoral response is an early event and that p53 antibodies can be used as a precocious marker of p53 alteration before clinical manifestation of the disease.

Adult↗
PubMed1995

[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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

[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↗
PubMed1993

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↗
PubMed1993

[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↗
PubMed1993

[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↗
PubMed1992

[Interstitial pulmonary involvements in polymyositis and dermatopolymyositis. Apropos of 3 cases. Review of the literature].

The authors report 3 cases of myositis associated with pulmonary lesions that preceded or succeeded the muscular disorder. In one of these cases, which was particularly difficult to diagnose, the patient's serum was positive for the anti-Jol antibody. These 3 cases have encouraged the authors to review the literature with particular attention to the diagnostic approach, the latest physiopathological data and the therapeutic basis of the "specific" pulmonary lesions associated with polymyositis and dermatomyositis.

Dermatomyositis↗
PubMed1991

[Pleuropulmonary cryptococcosis disclosing AIDS].

The authors report a case of AIDS revealed by pleuropulmonary cryptococcosis. The infection was diagnosed by culture of the pleural fluid and confirmed by microscopic examination of the cerebrospinal fluid, using Indian ink as stain. Apyrexia and return to normal of chest radiography were obtained with oral fluconazole. Twelve months after this episode the patient is alive and had no relapse under maintenance treatment with this drug.

Acquired Immunodeficiency Syndrome↗
PubMed1991

[Interstitial pulmonary involvement of polymyositis and dermatomyositis. Apropos of 3 cases. Review of the literature].

The authors report 3 new cases of myositis associated with pulmonary lesions that preceded or succeeded the muscular disorder. In one of these cases, which was particularly difficult to diagnose, the patient's serum was positive for the anti-Jo1 antibody. These 3 cases have encouraged the authors to review the literature with particular attention to the diagnostic approach, the latest physiopathological data and the therapeutic basis of the "specific" pulmonary lesions associated with polymyositis and dermatomyositis.

Adult↗