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C Brambilla

Publications and source records attributed to C Brambilla.

At least 73 records · Page 4Linked to original sources
PubMed1998

p53 mutant immunophenotype and deregulation of p53 transcription pathway (Bcl2, Bax, and Waf1) in precursor bronchial lesions of lung cancer.

Lung cancer is the end result of a multistep process in which genetic and molecular changes accompany, in an unknown temporal sequence, histological precursor (preinvasive) bronchial lesions. Biomarkers allowing prediction of the rate of progression of precursor lesions at different locations in the anatomical field may be clinically useful. Toward this aim, we analyzed, using immunohistochemistry, the expression of the p53 gene and of its transcriptional target genes bax, bcl2, and waf1 in preinvasive bronchial lesions from 69 patients with lung cancer and in similar lesions from 20 patients with no cancer progression. p53 accumulation occurred with increasing frequency, from 19% in mild dysplasia to 36% in moderate dysplasia and 59% in carcinoma in situ, and was exclusively observed in patients with p53-positive carcinoma. The higher frequency of the p53-positive immunophenotype in lesions adjacent to the p53-positive carcinoma, as compared to lesions distant from it, suggests that p53 mutant preneoplastic lesions had a higher rate of progression to invasion than did p53-negative lesions. Similar lesions in patients with no progression to lung cancer were all p53 negative. Bcl2 overexpression and Bax down-regulation, as shown by immunostaining, occurred in preinvasive lesions and were mainly maintained during invasion. The expressions of bax, bcl2, and waf1 did not correlate with p53 status. We conclude that p53 stabilization in preinvasive lesions has high predictive value for progression to invasion and that Bax/Bcl2 imbalance contributes to the clonal expansion during premalignant states.

Bronchial Neoplasms↗
PubMed1998

[Pleural granulocytic sarcoma. Apropos of a case and review of the literature].

The granulocytic sarcoma is a rare and extramedullary tumor, which is composed of granulocytic precursor cells. The diagnosis remains difficult. Infectious disease are often associated with leukemic processes. Combination of clinical, radiological and pathological findings are useful for diagnosis. On gross examination, the tumor appears green. The detection of myeloperoxidases and the presence of immature eosinophils can help histological analysis. Granulocytic sarcoma occurs before or during an acute leukemia. It is treated like an acute leukemia. Prognostic is greatly improved by early diagnosis and treatment. The lack of cytogenetic abnormalities is associated with a prolonged survival. We describe a new case of rapidly growing pleural granulocytic sarcoma. The uncommon modifications of chromosome 5 long arm in this case could explain the immature eosinophil reaction in that tumor.

Acute Disease↗
PubMed1998

[Acute eosinophilic pneumonia due to hypersensitivity to carbamazepine].

The authors report a case of hypersensitivity to carbamazepine presenting as an acute eosinophilic pneumonia and a probable hypersensitivity myopericarditis in a 54-year-old patient treated with carbamazepine for three weeks. Treatment consisted of stopping the carbamazepine and in prolonged corticosteroid therapy. The features of the hypersensitivity syndrome to carbamazepine are mentioned as well as the different pulmonary disorders attributable to carbamazepine.

Adrenal Cortex Hormones↗
PubMed1997

High-dose chemotherapy and autologous bone marrow transplantation compared with MACOP-B in aggressive B-cell lymphoma.

BACKGROUND: We compared a regimen of six chemotherapeutic agents administered sequentially at high doses, followed by myeloablative treatment and bone marrow transplantation, with a regimen of methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B) as initial or salvage treatment for adults with diffuse large-cell lymphoma. METHODS: Ninety-eight eligible patients with diffuse large-cell lymphoma of the B-cell type were randomly assigned to receive either MACOP-B (50 patients) or high-dose sequential therapy (48 patients). The study design allowed for patients in whom the assigned treatment failed to cross over to the other treatment group. RESULTS: After a median follow-up of 55 months, the patients given high-dose sequential therapy, as compared with those treated with MACOP-B, had significantly higher rates of complete response (96 percent vs. 70 percent, P=0.001), freedom from disease progression (84 percent vs. 49 percent, P<0.001), freedom from relapse (88 percent vs. 70 percent, P=0.055), and event-free survival (76 percent vs. 49 percent, P=0.004). The difference in overall survival at seven years, which also favored the group assigned to high-dose sequential therapy, was marginally significant (81 percent vs. 55 percent, P=0.09). CONCLUSIONS: High-dose sequential therapy is superior to standard-dose MACOP-B for patients with diffuse large-cell lymphoma of the B-cell type.

Adolescent↗
PubMed1997

Central airway stenoses: preliminary results of spiral-CT-generated virtual bronchoscopy simulations in 29 patients.

The purpose of this study was to determine the feasibility of using virtual bronchoscopy simulations to depict stenoses of the tracheobronchial tree. Virtual bronchoscopy simulations, based on ray casting, were applied to spiral-CT data sets of 29 patients presenting 41 stenoses of the central airways, proved with fiberoptic bronchoscopy. Simulations of the inner walls of the airways were of good quality in 27 of 29 patients. Airway stenoses were depicted in 39 of 41 cases. Evaluation of the length of stenoses and surrounding tissues required simultaneous display of multiplanar reformations. Virtual bronchoscopy provides a valuable road map for bronchoscopy, in an image format familiar to bronchoscopists.

Adult↗
PubMed1997

Two-step immunoscintigraphy for non-small-cell lung cancer staging using a bispecific anti-CEA/anti-indium-DTPA antibody and an indium-111-labeled DTPA dimer.

UNLABELLED: Immunoscintigraphy (IS) using anti-CEA F(ab')2 monoclonal antibody (MAb) is useful for improving mediastinal staging of nonsmall cell lung cancer (NSCLC), but the technique was limited because of an insufficient contrast between tumor and normal tissues. The aim of this study was to determine if the method could be improved by a two-step method which uses a bispecific anti-CEA/anti-di-DTPA antibody (Bs-MAb) and 111In-labeled di-DTPA-tyrosyl-lysine bivalent hapten. METHODS: Twelve patients were intravenously given a 30 min Bs-MAb infusion (0.1 mg/kg). Four days later, they were injected intravenously with 0.1 microgram/kg hapten labeled with 185 MBq 111In (5 mCi). Images were recorded immediately and 6 and 24 hr after hapten injection. A pharmacokinetic analysis was performed. Surgery was performed 3 days after 111In-hapten injection, and samples of tumor and normal tissues were collected for immunohistochemical and biodistribution studies. IS results were classified as true-positive (TP), false-positive (FP), true-negative (TN) or false-negative (FN) according to the surgical data. RESULTS: Primary tumors were visualized in nine patients. The contrast was excellent, generally higher than that obtained with direct labeling of anti-CEA. In the mediastinum, IS results were (after surgery) five TN, two TP and one FP. One case remains undetermined. The FP result was due to a Bs-MAb uptake in intrapulmonary lymph nodes. IS was in agreement with preoperative staging in six of these nine patients and discordant in three. CONCLUSION: Our study confirmed that the two-step method with a bispecific antibody could greatly improve the performances of IS for lung cancer staging.

Antibodies, Bispecific↗
PubMed1997

Expression of urokinase-type plasminogen activator, stromelysin 1, stromelysin 3, and matrilysin genes in lung carcinomas.

We have previously shown that the extracellular-matrix-degrading enzymes, urokinase-type plasminogen activator (u-PA), stromelysin 1, stromelysin 3, and matrilysin, may play an important role in the transition from lung preneoplasia to invasive carcinoma. Using in situ hybridization and immunohistochemistry, we analyzed serial frozen sections for the expression of these enzymes in 89 lung carcinomas including 25 neuroendocrine (NE) carcinomas (10 small-cell lung carcinomas, 7 large-cell NE carcinomas, 1 atypical, and 7 typical carcinoids) and 64 non-small-cell, non-NE carcinomas (29 squamous and 7 basaloid carcinomas, 23 adenocarcinomas, and 5 large-cell carcinomas). Proteases, except matrilysin, were more often expressed in stromal than cancer cells. In non-small-cell, non-NE carcinomas, stromal co-expression of u-PA and stromelysin 3 was seen in 80 to 90% of the tumors and was highly correlated (P < 0.0001). Stromal u-PA and stromelysin 3 expression was linked to tumor size (P = 0.01 and 0.03, respectively) and lymph node involvement (P = 0.001 and 0.02, respectively). Epithelial expression of u-PA was correlated to tumor size (P = 0.04). Epithelial expression of stromelysin 3 predominated in squamous and basaloid carcinomas (P = 0.0005) and was inversely correlated to squamous differentiation (P = 0.018). Epithelial expression of matrilysin predominated in adenocarcinomas and large-cell carcinomas (P = 0.07). In NE carcinomas including small-cell lung carcinomas, stromal expression of u-PA was correlated to lymph node metastasis (P = 0.017). Epithelial expression of all enzymes were significantly less frequent in NE than in non-NE tumors. We conclude that 1) epithelial expression of matrix proteases in lung cancer is linked to cell phenotype (NE versus non-NE, squamous versus glandular) and 2) their stromal, rather than epithelial, expression influences local metastasis.

Carcinoma↗
PubMed1997

[Evaluation of survival and prognostic factors of 2,000 broncho-pulmonary cancers registered during 10 years in a multidisciplinary oncology department].

Two thousand lung cancer patients were registered as Grenoble's university hospital joint oncology clinic from 1/1/1982 to 12/31/1991. These cases consisted of 449 small cell lung cancers (SCLC) and 1,551 non-small cell lung cancers (NSCLC). SCLC patients had a 4.6% and 2.9% survival rate at 5 and 10 years and only 7.2% of patients had a survival longer than 30 months. The main prognostic factors for survival were age, sex, TNM stage and WHO performance status. There was no increase in survival during the 2 periods of the study. NSCLC patients had a 14% and 7% survival rate at 5 and 10 years. Among 727 stage III or IV patients not treated with surgery, 2% were alive at 30 months. The main prognostic factors for survival were age, histology, TNM stage and WHO performance status. There was no increase in survival during the 2 periods of the study.

Adult↗
PubMed1997

[Cushing syndrome and small cell carcinoma. Three case reports].

Paraneoplastic Cushing's syndrome associated with small cell carcinoma is a poor prognosis factor. Opportunistic infections are an important factor of morbidity and mortality. Therefore antiadrenal medications are necessary before initiating cytotoxic chemotherapy. The report of three recent cases will emphasize the need of special management of this disease.

Adult↗
PubMed1997

[Pulmonary epithelioid hemangioendothelioma (or IVBAT). Report of a case of exclusively myxoid form].

Epithelioid hemangioendothelioma of the lung, therefore labeled as IntraVascular BronchioAlveolar Tumor (IVBAT), is a tumor of endothelial origin; its presentation with multiple pulmonary nodules radiographically suggests metastatic disease. We describe here an epithelioid hemangioendothelioma with an exclusively myxoid pattern. The tumor was composed of nodules extending in a polypoid fashion from the alveolar septa. The cells within the tumor were epithelial-like and contained cytoplasmic lacunae positive for anti-FVIII, CD31 and CD34 antibodies. According to usual criteria, it was considered as a tumor of low grade malignancy, without vascular or bronchiolar extension or cytonuclear atypia and mitosis; the prognosis, difficult to determine, depends on locoregional tumor progression.

Hemangioendothelioma, Epithelioid↗
PubMed1997

[Pulmonary inflammatory pseudotumor complicating the course of a community-acquired pneumopathy. A deceptive radio-clinical presentation].

The case of a 46 years old man presenting a chronic history of right upper lobe pneumonia is reported. The clinical presentation associated with nodular pulmonary computed tomographic scan lesions, highly suggested a malignant bronchopulmonary process. A lobectomy was performed. Histological analysis revealed an inflammatory pseudotumor. This inflammatory process may be a particular end stage disease of pulmonary infectious disease.

Biopsy↗
PubMed1997

[Lymphocytic alveolitis, chronic viral hepatitis C, lipoproteinosis and cryoglobulinemia in a patient].

Chronic hepatitis C virus (HCV) infection, lipoproteinosis and cryoglobulinemia may all be associated with lymphocyte alveolitis. The pathogenic mechanisms involved would suggest a compromised immune system. We report the first observation of a patient with lipoproteinosis, cryoglobulinemia and hepatitis C virus infection who developed lymphocyte alveolitis. Taken individually, each of these three disease states could explain cellular modifications observed in the lung, but their association aggravated the clinical course.

Cryoglobulinemia↗
PubMed1997

p53 and lung cancer.

The malignant transformation of pulmonary epithelial cells is the result of multistep accumulation of genetic and molecular alterations highly related to tobacco carcinogens, involving key mechanisms of proliferation and apoptosis. Clonal expansion is the net result of acceleration of cell division and inhibition of active cell death (apoptosis). Oncogene activation in lung cancer (ras, myc, autocrine growth factor loops) results in acceleration of cell division. More importantly, tumor suppressor genes inactivation (p53, Rb, cyclin-dependent-kinase-Inhibitor p16) at genetic, epigenetic, or post-translational level removes important constraints on cell division at G1-check-point increasing cell proliferation. p 53 inactivation, through loss of transcription function may abrogate both G1-arrest control and apoptosis, thus accelerating clonal expansion. It is the most frequent alteration in lung cancer (70% of genetic alterations) with some differentiation dependent differences. p53 missense mutation is highly concordant with p53 stabilization and immunoreactivity. However, 20% of mutations with null phenotype (no p53 protein) provides 20% of false negative using immunohistochemistry for evaluation of p53 mutations in lung cancer. Rare situations are described with wild type p53 stabilization. p53 mutational spectrum in lung cancer reveals some specificities: 3 hot spot codons (codon 157, 248, 273) are the main target of selective adduct formation from a defined chemical carcinogen of cigarette smoke (BP). p53 stabilized mutants proteins are the targets for immune recognition in patients, leading to secretion of p53 auto-antibodies, and can also elicit T-cell specific cytotoxicity in vitro. p53 was not proven to be of prognostical importance once the tumor has developed. However, p53 stabilization is one of the best predictor of progression and irreversitiblity of preneoplastic bronchial lesion overwhelming morphological changes such as severe dysplasia. Restoration of wild type p53 function through p53 gene therapy, immunotherapy or modification of carboxy terminal end enable new therapeutic intervention. Finally, target genes and proteins situated on the downstream pathway of p53 transcription appears to be the most important factors of growth acceleration or even cell dissemination in lung cancer (Rb and its phosphorylation pathway, Bax-Bc12 balance and matrix degrading enzymes UPA and inhibitor PAI). Their constitutive deregulation could by-pass wild type p53 functions. p53 pathway offers several targets for future gene therapy or modulation in the future in lung cancer.

Antigens, Neoplasm↗
PubMed1996

Vinorelbine: an active, non cross-resistant drug in advanced breast cancer. Results from a phase II study.

PURPOSE: To evaluate efficacy and toxicity of vinorelbine and to investigate its cross-resistance with other current drug treatments for metastatic breast cancer. PATIENTS AND METHODS: From July 1992 to December 1993, 57 histologically proven breast cancer patients entered this Phase II study. Patients were stratified according to their status of previous treatment, namely, no prior chemotherapy or relapse more than 12 months since the end of adjuvant chemotherapy (Group A) and other patients (Group B). RESULTS: Fifty three patients were evaluable for response, 27 in Group A and 26 in Group B. All patients were evaluable for toxicity. Vinorelbine was initially administered at the dose of 30 mg/sqm weekly by i.v. infusion in 100 ml of normal saline over 20 minutes. A frequency analysis of drug administration in the first 20 cases revealed two main treatment periodicities, corresponding to one week and to three weeks. Thereafter the drug was administered at 30 mg/sqm on day 1 and 8, every 3 weeks. With the new drug schedule, the mean dose intensity increased from 19.7 to 21.1 mg/sqm per week. Overall, an objective response rate of 47% (95% C.I. 33%-61%) was documented. Four patients achieved complete response (7%, CI: 2%-18%) and 21 partial response (40%, CI: 26%-54%). Fifty nine percent of patients in Group A and 35% in Group B showed objective tumor response. The analysis of response rate in previously treated patients failed to show evidence of cross-resistance with vinorelbine. Main side effects, i.e. neutropenia, local pain, and gastrointestinal and flu-like symptoms, were moderate and short lasting. CONCLUSION: Vinorelbine has clinically significant activity in metastatic breast cancer, and no cross-resistance with prior anthracyclines and CMF treatments. The drug schedule of 30 mg/sqm iv bolus on day 1 and 8 every 3 weeks was found effective and tolerable.

Adult↗
PubMed1996

In situ apoptotic cell labeling by the TUNEL method: improvement and evaluation on cell preparations.

TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling) is a method of choice for rapid identification and quantification of the apoptotic cell fraction in cultured cell preparations. However, TUNEL application has been restricted to a narrow spectrum of sample conditions, and only detergents have been proposed as labeling enhancers. This study was aimed at extending TUNEL to variously fixed cells and improving TUNEL sensitivity by optimized pretreatments, the specificity being assessed by reference to the apoptotic morphology. Comparative TUNEL was performed with three protocols on CEM-C7 cells, a model of glucocorticoid-induced apoptosis. Samples were submitted to six modalities of fixation and TUNEL was performed after each of the following conditions: no pretreatment; detergent permeabilization; proteolytic digestion; microwave irradiation; and a recently published combination of the latter two. The proportion of TUNEL-stained elements within the cell fraction, with and without apoptotic morphology, was quantified. Our results showed that: (a) with an adequate pretreatment, reliable TUNEL can be obtained after each fixative tested; (b) detergent was inefficient in improving sensitivity; (c) whatever the fixation, microwave pretreatment provided the best TUNEL sensitivity without notable loss of specificity; (d) under adaptive technical conditions, TUNEL can be associated with detection of various proteins by double labeling; and (e) the existence of a limited population of intensely TUNEL-positive cells that lacked apoptotic morphology contributes to the current debate about a preapoptotic state.

Apoptosis↗
PubMed1996

Accuracy of oximetry for detection of respiratory disturbances in sleep apnea syndrome.

STUDY OBJECTIVE: The cost and inconvenience of polysomnography make simplified techniques of screening desirable in the strategy of diagnosis of sleep apnea syndrome (SAS). We have evaluated, in a prospective study of 301 consecutive patients referred for suspected sleep disorders, an index (delta index) that detects apneic events by quantifying arterial oxygen saturation (SaO2) variability. SETTING: Regional sleep laboratory taking referrals from general practitioners and specialists. DESIGN: Classic polysomnography was the gold standard, with 15 apneas plus hypopneas per hour (RDI) being used as a threshold for definition of obstructive sleep apnea (OSA). Oximetry was recorded over the same night. Signal variability was quantified as a function of time, using digital processing of oximetric data. Sensitivity, specificity, and positive and negative predictive values of oximetry testing were calculated. A receiver operating characteristic (ROC) curve was constructed representing the comparative courses of sensitivity and 1-specificity at different thresholds of delta index. RESULTS: Three hundred one patients were included (age, 56 +/- 12 years). Their RDI was 30 +/- 24. For a delta threshold at 0.6, the sensitivity of oximetry for the diagnosis of OSA was 98% and the specificity was 46%. The positive and negative predictive values for diagnosing SAS were 77% and 94%, respectively. The three false-negative cases had a relatively high awake SaO2 (97 vs 93.9 +/- 2.8%), a moderate RDI (23.3 +/- 1.6), and were less obese than the other patients (body mass index: 25 +/- 3 vs 33 +/- 8). The 58 false-positive cases had an RDI of 8 +/- 4, an awake SaO2 of 93.1 +/- 3.6 vs 94.1 +/- 2.6 for the rest of the population (p = 0.01). Finally, the false-positive cases had more airways obstruction (FEV1/VC = 72 +/- 13 vs 77 +/- 15%; p = 0.026). Using a delta value of 0.8 leads to a sensitivity of 90% with 19 false-negative cases but with a higher specificity of 75%. CONCLUSIONS: A nocturnal oximetry test with a delta index below 0.6 is helpful in ruling out the diagnosis of SAS in patients being screened for this condition, as this yielded only three negative test results in 301 screening procedures.

Aged↗
PubMed1996

Long-term oxygen therapy at home. Compliance with medical prescription and effective use of therapy. ANTADIR Working Group on Oxygen Therapy. Association Nationale de Traitement à Domicile des Insuffisants Respiratories.

STUDY OBJECTIVE: Daily duration of oxygen administration is an important factor in the effectiveness of long-term oxygen therapy (LTOT) for hypoxic chronic pulmonary disease. We have assessed the daily use of oxygen therapy in 930 patients with COPD and examined factors associated with the effective use of this treatment. METHODS: Objective daily duration of oxygen use over a 3-month period was prospectively measured using the counter clock of the oxygen concentrators or by weighing the liquid oxygen container at each delivery. A questionnaire was filled in by an independent investigator asking about home situation, lifestyle, and whether oxygen therapy was used during all domestic and outside activities. In addition, prescribing physicians were asked about the duration and modalities of oxygen prescribed in each case. RESULTS: The patients had been receiving LTOT for 36 +/- 24 months and had hypoxemia (PaO2 = 56 +/- 9 mm Hg), hypercapnia (PaCO2 = 47 +/- 8 mm Hg), and severe airflow obstruction (FEV1/VC = 42 +/- 14%). The mean duration of oxygen treatment prescribed was 16 +/- 3 h/d. The mean duration of oxygen therapy achieved was 14.5 +/- 5 h, but only 45% of the patients achieved oxygen therapy for 15 h or more per day. Patients with effective use of LTOT, ie receiving oxygen therapy for at least 15 h/d, were significantly more hypoxic (PaO2 = 54 +/- 9 vs 57 +/- 9 mm Hg; p < 0.001), more hypercapnic (PaCO2 = 48 +/- 8 vs 46 +/- 7 mm Hg; p < 0.005), and also more obstructed (FEV1/VC = 39.5 +/- 13 vs 45 +/- 14%; p < 0.001) than the rest of the patients under treatment. Other factors associated with effective use of oxygen were (1) initial prescription for 15 h or more per day, (2) supplementary education on oxygen therapy by a nurse or physiotherapist, (3) cessation of smoking, (4) use of oxygen in all domestic situations (toilet, meals, leisure, etc.), and (5) absence of side effects from oxygen treatment. CONCLUSIONS: Attention by the prescribing physicians to such factors could optimize oxygen prescription and constitute goals for education of patients.

Adult↗