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1.
Acta Neuropathol ; 126(1): 123-35, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23400299

ABSTRACT

Pituitary adenomas are currently classified by histological, immunocytochemical and numerous ultrastructural characteristics lacking unequivocal prognostic correlations. We investigated the prognostic value of a new clinicopathological classification with grades based on invasion and proliferation. This retrospective multicentric case-control study comprised 410 patients who had surgery for a pituitary tumour with long-term follow-up. Using pituitary magnetic resonance imaging for diagnosis of cavernous or sphenoid sinus invasion, immunocytochemistry, markers of the cell cycle (Ki-67, mitoses) and p53, tumours were classified according to size (micro, macro and giant), type (PRL, GH, FSH/LH, ACTH and TSH) and grade (grade 1a: non-invasive, 1b: non-invasive and proliferative, 2a: invasive, 2b: invasive and proliferative, and 3: metastatic). The association between patient status at 8-year follow-up and age, sex, and classification was evaluated by two multivariate analyses assessing disease- or recurrence/progression-free status. At 8 years after surgery, 195 patients were disease-free (controls) and 215 patients were not (cases). In 125 of the cases the tumours had recurred or progressed. Analyses of disease-free and recurrence/progression-free status revealed the significant prognostic value (p < 0.001; p < 0.05) of age, tumour type, and grade across all tumour types and for each tumour type. Invasive and proliferative tumours (grade 2b) had a poor prognosis with an increased probability of tumour persistence or progression of 25- or 12-fold, respectively, as compared to non-invasive tumours (grade 1a). This new, easy to use clinicopathological classification of pituitary endocrine tumours has demonstrated its prognostic worth by strongly predicting the probability of post-operative complete remission or tumour progression and so could help clinicians choose the best post-operative therapy.


Subject(s)
Pituitary Gland/pathology , Pituitary Neoplasms/classification , Pituitary Neoplasms/pathology , Adolescent , Adult , Age Factors , Aged , Case-Control Studies , Disease-Free Survival , Female , Humans , Longitudinal Studies , Magnetic Resonance Imaging , Male , Middle Aged , Pituitary Gland/ultrastructure , Pituitary Neoplasms/surgery , Prognosis , Recurrence , Retrospective Studies , Sensitivity and Specificity , Sex Factors , Young Adult
2.
Respiration ; 85(2): 156-9, 2013.
Article in English | MEDLINE | ID: mdl-23095475

ABSTRACT

Airway-centered interstitial fibrosis (ACIF) is a distinct type of lung interstitial fibrosis characterized by lesions centered on the airways. Several cases reported in the literature showed little to no effect of corticosteroids and a high mortality rate in the absence of lung transplantation. No other efficient approach is described for the treatment of this type of fibrosis. We report for the first time the case of a 44-year-old patient diagnosed with ACIF on surgical lung biopsy and stabilized with clarithromycin after failure of systemic corticosteroids. We need to confirm this benefit in other patients to ascertain the anti-inflammatory effect of macrolides, which are far less harmful compared to corticosteroids or immunosuppressant drugs.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Clarithromycin/therapeutic use , Lung Diseases, Interstitial/drug therapy , Pulmonary Fibrosis/drug therapy , Adult , Enzyme Inhibitors , Esomeprazole/adverse effects , Glucocorticoids/adverse effects , Humans , Lung Diseases, Interstitial/diagnostic imaging , Male , Prednisolone/adverse effects , Pulmonary Fibrosis/pathology , Radiography , Respiratory Function Tests , Treatment Failure
3.
Rev Pneumol Clin ; 68(5): 295-9, 2012 Oct.
Article in French | MEDLINE | ID: mdl-22749619

ABSTRACT

Intra-alveolar hemorrhage (IAH) could be revealed by acute respiratory failure. The classic association of hemoptysis - anemia - radiological infiltrates is suggestive and has to be confirmed by broncho-alveolar lavage with Golde score. Etiologies included immune and non-immune diseases, with specific treatment for each. We report a case of IAH revealed by acute respiratory distress syndrome and anemia (3 g/dL), related to pulmonary and cerebral vasculitis without renal involvement. The patient was efficiently treated with corticosteroids and cyclophosphamide. This case highlights the critical role of BAL cytological analysis with Golde score, and the need for a rapid and accurate diagnosis in order to guide specific treatment. If histology is needed, renal biopsy even without renal involvement, or surgical lung biopsy is possible.


Subject(s)
Bronchial Diseases/complications , Hemorrhage/complications , Respiratory Distress Syndrome/etiology , Vasculitis/complications , Bronchial Diseases/diagnosis , Bronchial Diseases/diagnostic imaging , Diagnosis, Differential , Female , Hemorrhage/diagnosis , Hemorrhage/diagnostic imaging , Humans , Middle Aged , Pulmonary Alveoli/pathology , Radiography, Thoracic , Respiratory Distress Syndrome/diagnosis , Respiratory Distress Syndrome/diagnostic imaging , Vasculitis/diagnosis , Vasculitis/diagnostic imaging
4.
Ann Oncol ; 23(6): 1555-61, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22012966

ABSTRACT

BACKGROUND: There is no consensual first-line chemotherapy for elderly patients with mantle cell lymphoma (MCL). The GOELAMS (Groupe Ouest-Est des Leucémies Aiguës et Maladies du Sang) group previously developed the (R)VAD+C regimen (rituximab, vincristine, doxorubicin, dexamethasone and chlorambucil), which appeared as efficient as R-CHOP (rituximab, cyclophosphamide, doxorubicine, vincristine, prednisone) while less toxic. Based on this protocol, we now added bortezomib (RiPAD+C: rituximab, bortezomib, doxorubicin, dexamethasone and chlorambucil) given its efficacy in relapsed/refractory MCL patients. The goal of the current phase II trial was to evaluate the feasibility and efficacy of the RiPAD+C regimen as frontline therapy for elderly patients with MCL. PATIENTS AND METHODS: Patients between 65 and 80 years of age with newly diagnosed MCL received up to six cycles of RiPAD+C. RESULTS: Thirty-nine patients were enrolled. Median age was 72 years (65-80). After four cycles of RiPAD+C, the overall response rate was 79%, including 51% complete responses (CRs). After six cycles, CR rate increased up to 59%. After a 27-month follow-up, median progression-free survival (PFS) is 26 months and median overall survival has not been reached. Four patients (10%) discontinued the treatment because of a severe toxicity and seven patients (18%) experienced grade 3 neurotoxicity. CONCLUSION: The bortezomib-containing RiPAD+C regimen results in high CR rates and prolonged PFS with predictable and manageable toxic effects in elderly patients with MCL.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma, Mantle-Cell/drug therapy , Aged , Aged, 80 and over , Antibodies, Monoclonal, Murine-Derived/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Boronic Acids/administration & dosage , Bortezomib , Chlorambucil/administration & dosage , Dexamethasone/administration & dosage , Disease-Free Survival , Doxorubicin/administration & dosage , Female , Humans , Kaplan-Meier Estimate , Lymphoma, Mantle-Cell/mortality , Male , Pyrazines/administration & dosage , Rituximab , Treatment Outcome
5.
Int J Immunopathol Pharmacol ; 19(3): 471-87, 2006.
Article in English | MEDLINE | ID: mdl-17026855

ABSTRACT

Pulmonary fibrosis is characterized by the excessive deposition of extracellular matrix in the interstitium, resulting in respiratory failure. The role of remodeling mediators such as metalloproteinases (MMPs) and their inhibitors (TIMPs) in the fibrogenic process remains misunderstood. We investigated MMP-9, MMP-2, TIMP-1, TIMP-2 and TIMP-3 in the fibrotic response to bleomycin of fibrosis prone C57BL/6J and fibrosis resistant BALB/c mice. Mice were administered with 0.1 mg bleomycin by intranasal administration. Either 24 h or 14 days after, the mice were anesthetized and underwent either bronchoalveolear lavage (BAL) or lung removal. Collagen deposition in lung tissue was determined by hydroxyproline measurement, MMP activity was analyzed by zymography, and other mediators were analyzed by ELISA. TIMP-1 was localized in lung sections by immunohistochemistry and real time PCR was performed to gene expression in lung. Non parametric Mann-Whitney and Spearman tests were used for statistical analysis. Fourteen days after bleomycin administration, hydroxyproline assay and histological study revealed that BALB/c mice developed significantly less fibrosis compared to C57BL/6J mice. At day 1, bleomycin enhanced TIMP-1, MMP-2 and MMP-9 protein levels in BALF, and induced corresponding genes in lung tissue of both strains. The rise of Timp-1, Mmp-9 and Mmp-2 gene levels were significantly stronger in lungs of C57BL/6J, whereas gelatinase activities of MMP-2 and MMP-9 were similar. Immunohistochemistry revealed that TIMP-1 macrophages and epithelial cells were prominent TIMP-1 producers in both strains. At day 14, neither MMP-2 nor MMP-9 levels exhibited strain-dependent protein level or gene expression, although TIMP-1 was strongly associated with fibrosis. Interestingly, bleomycin induced neither Timp-2 nor Timp-3 in lung tissue at any time of the study. The present study shows that early altered regulation of TIMP-1 following bleomycin administration may be involved in bleomycin-induced pulmonary fibrosis.


Subject(s)
Bleomycin/toxicity , Pulmonary Fibrosis/chemically induced , Tissue Inhibitor of Metalloproteinase-1/physiology , Animals , Bronchoalveolar Lavage Fluid/cytology , Collagen/metabolism , Interleukin-6/analysis , Interleukin-6/genetics , Male , Matrix Metalloproteinase 2/analysis , Matrix Metalloproteinase 2/genetics , Matrix Metalloproteinase 9/analysis , Matrix Metalloproteinase 9/genetics , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , RNA, Messenger/analysis , Tissue Inhibitor of Metalloproteinase-1/analysis , Tissue Inhibitor of Metalloproteinase-1/genetics
6.
Clin Infect Dis ; 43(5): 577-84, 2006 Sep 01.
Article in English | MEDLINE | ID: mdl-16886149

ABSTRACT

BACKGROUND: Invasive aspergillosis is an opportunistic infection that occurs mainly among patients with prolonged neutropenia. Few data are available on invasive aspergillosis in nonneutropenic patients. METHODS: The aim of this survey was to compare neutropenic and nonneutropenic patients who had received a diagnosis of invasive aspergillosis at our institution during a 6-year period. RESULTS: Among the 88 cases of invasive aspergillosis analyzed here, 12 were histologically proven, 52 were probable, and 24 were possible. Forty-seven percent of cases were diagnosed in the intensive care unit, and 40% were diagnosed in hematology units. Neutropenia was a risk factor for 52 patients (59%), most of whom had hematological or solid malignancies. Among the 36 nonneutropenic patients (41%), the main underlying conditions were steroid-treated chronic obstructive pulmonary disease, asthma, rheumatoid arthritis, giant-cell arteritis, and microvascular disorders; 10 patients were recipients of solid-organ transplants, and 1 patient was seropositive for human immunodeficiency virus. The distribution of proven and probable invasive aspergillosis was similar for neutropenic and nonneutropenic patients. The mortality rate was 71.5% overall and was significantly higher among nonneutropenic patients than among neutropenic patients (89% vs. 60%; P<.05). Compared with neutropenic patients, nonneutropenic patients were significantly less likely to have symptoms of invasive aspergillosis and more likely to have frequent intercurrent pneumonia due to another microorganism. The sensitivity of mycological examination of bronchoalveolar lavage fluid specimens was higher for nonneutropenic patients than for neutropenic patients (85% vs. 58%; P<.05), whereas the sensitivity of antigenemia was the same for the 2 populations (65% vs. 64%). Findings on thoracic computed tomographs were similar, except that segmental areas of consolidation occurred more frequently among neutropenic patients. CONCLUSION: This survey at a whole institution underlines the high number of cases of invasive aspergillosis among nonneutropenic patients, with an overall mortality rate that was significantly higher than that for neutropenic patients.


Subject(s)
Aspergillosis/epidemiology , Aspergillosis/pathology , Neutropenia/complications , Adolescent , Adult , Aged , Antibodies, Fungal/blood , Antifungal Agents/therapeutic use , Antigens, Fungal/blood , Aspergillosis/complications , Aspergillosis/drug therapy , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Risk Factors , Time Factors
7.
Rev Mal Respir ; 21(1): 137-40, 2004 Feb.
Article in French | MEDLINE | ID: mdl-15260048

ABSTRACT

INTRODUCTION: Erosion of mediastinal adenopathy into the bronchial tree is classically associated with tuberculosis. We describe two cases of of such bronchial erosion with Hodgkin's disease. CASE REPORT: The first case was of a seventy-year old man with a history of pulmonary silicosis. A sub-carenal mass was identified during investigation of chronic cough. The bronchoscopy revealed an inflammatory stenosis due to Hodgkin's disease. The second case was of a thirteen-year old child whose Hodgkin's disease was thought to be in remission following treatment. The erosion of mediastinal adenopathy into the main left bronchus produced complete left pulmonary atalectasis, which required endobronchial stenting. CONCLUSIONS: In both cases, rigid bronchoscopy provided a histological diagnosis with diagnosis of Hodgkin's disease in the first case, and identification of recurrence in the other one. These cases are unusual. Such complications are usually complications of radiotherapy. Classically, erosion of mediastinal adenopathy into the bronchial tree is tuberculous in origin but they can be neoplasic.


Subject(s)
Bronchial Fistula/etiology , Fistula/etiology , Hodgkin Disease/complications , Lymphatic Diseases/etiology , Mediastinal Diseases/etiology , Adolescent , Aged , Female , Humans , Male
9.
Eur J Nucl Med Mol Imaging ; 31(4): 542-6, 2004 Apr.
Article in English | MEDLINE | ID: mdl-14691613

ABSTRACT

Although intra-arterial radiotherapy with (131)I-labelled lipiodol is a useful therapeutic approach in the treatment of hepatocellular carcinomas, various disadvantages limit its use. Here we describe the development of (188)Re-SSS lipiodol, as well as its biodistribution in the healthy pig after injection into the hepatic artery. The (188)Re-SSS lipiodol was obtained after dissolving a chelating agent, previously labelled with (188)Re, in cold lipiodol. The radiochemical purity (RCP) of the labelling was checked immediately and at 24 and 48 h. The (188)Re-SSS lipiodol was injected into the hepatic artery of six healthy pigs. They were killed 1, 24 and 48 h post injection, for ex vivo counting. An autoradiographic study was performed in three cases. (188)Re-SSS lipiodol was obtained with a yield of 87%+/-9.1%. The immediate RCP was 93%+/-3.4%. This radiolabelling was reproducible and stable at 48 h in plasma: 90.6%+/-1.5% of the activity remained in the lipiodol with an RCP of 91%+/-4%. Ex vivo counting confirmed the predominantly hepatic uptake and revealed weak lung and intestinal uptake. There was very weak urinary elimination (2.3%+/-0.5% at 48 h) and a slightly higher level of intestinal elimination (4.8%+/-1.9% at 48 h). The autoradiographic studies showed (188)Re-SSS lipiodol to be located mainly in sinusoids, like (131)I-lipiodol. By using the method described here, (188)Re-SSS lipiodol can be obtained with a very high yield and a satisfactory RCP. Its biodistribution in the healthy pig is in agreement with data published elsewhere concerning other types of radiolabelling used for lipiodol, except for the very weak urinary and intestinal elimination, which probably indicates better stability of (188)Re-SSS labelling.


Subject(s)
Hepatic Artery/metabolism , Iodized Oil/administration & dosage , Iodized Oil/pharmacokinetics , Liver/blood supply , Liver/metabolism , Organometallic Compounds/administration & dosage , Organometallic Compounds/pharmacokinetics , Animals , Carcinoma, Hepatocellular/radiotherapy , Drug Combinations , Feasibility Studies , Injections, Spinal , Isotope Labeling/methods , Liver/diagnostic imaging , Liver Neoplasms/radiotherapy , Metabolic Clearance Rate , Organ Specificity , Radionuclide Imaging , Radiopharmaceuticals/administration & dosage , Radiopharmaceuticals/chemical synthesis , Radiopharmaceuticals/pharmacokinetics , Swine , Tissue Distribution
10.
Clin Exp Allergy ; 33(5): 696-704, 2003 May.
Article in English | MEDLINE | ID: mdl-12752601

ABSTRACT

BACKGROUND: Chronic asthma is characterized by inflammatory cell infiltration and tissue remodelling leading to subepithelial fibrosis. Metalloproteinases (MMPs) are involved in degradation of extracellular matrix in most chronic inflammatory diseases. OBJECTIVE: The aim of this study was to investigate the expression of MMPs in the development of inflammatory processes associated or not with the concomitant development of subepithelial fibrosis in an experimental model of asthma. METHODS: Sensitized BP2 mice were challenged with ovalbumin (OA) every 2 weeks during 8 months. Several mice were removed once a month and bronchoalveolar lavages (BAL) or lung biopsies were performed. RESULTS: Lung sections stained with picrosirius and hydroxyproline measurements showed a significant collagen deposition after 16 weeks of OA challenge, demonstrating the development of subepithelial fibrosis. Pulmonary inflammation was present from the first OA challenge and was consistent throughout the 8 months of the study. Moreover, an up-regulation and activation of MMP-9 and, to a less extent, MMP-2 were observed in BAL fluid from challenged mice. The level of tissue inhibitor of metalloproteinases (TIMP)-1 increased after 12 weeks of OA challenge vs. control mice. CONCLUSION: This study reveals that a decrease in the activation of the MMP-9 due to the increase in TIMP-1, could contribute to excessive collagen deposition following repeated antigen challenge in sensitized mice.


Subject(s)
Asthma/enzymology , Gelatinases/metabolism , Pulmonary Fibrosis/enzymology , Animals , Asthma/complications , Asthma/pathology , Bronchoalveolar Lavage Fluid/cytology , Cell Count , Chronic Disease , Cytokines/biosynthesis , Disease Models, Animal , Hydroxyproline/metabolism , Male , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Mice , Ovalbumin/immunology , Pulmonary Fibrosis/etiology , Pulmonary Fibrosis/pathology , Tissue Inhibitor of Metalloproteinase-1/metabolism , Tissue Inhibitor of Metalloproteinase-2/metabolism
11.
Rev Med Interne ; 23(3): 317-21, 2002 Mar.
Article in French | MEDLINE | ID: mdl-11928380

ABSTRACT

INTRODUCTION: Tracheo-bronchial amyloidosis is an uncommon localized form of amyloidosis. We report two new cases. EXEGESIS: Two patients had developed expiratory dyspnea for several months. CT-scan and flexible bronchoscopy confirmed tracheal narrowing and a diagnosis of tracheo-bronchial amyloidosis was made by tissue biopsies. The immunohistochemical type was AL in one case, undetermined in the other case. There was no argument for systemic involvement. The two patients benefited from bronchoscopic dilatation. This treatment improved clinical symptoms and pulmonary function tests with a follow up of 12 and 18 months respectively. CONCLUSION: Tracheo-bronchial amyloidosis is a localised form of amyloidosis with various respiratory symptoms. Diagnosis is made by CT-scan and flexible bronchoscopy that allows biopsies. Immunohistochemical type is more often AL. Recurrence, respiratory insufficiency and tracheo-bronchial metaplasia are the most important complications. Treatment consists of bronchoscopic dilatation or excision, and bronchoscopic laser-YAG. Pulmonary function testing allows precise follow-up.


Subject(s)
Amyloidosis , Bronchial Diseases , Tracheal Diseases , Aged , Amyloidosis/diagnosis , Amyloidosis/diagnostic imaging , Amyloidosis/pathology , Amyloidosis/therapy , Biopsy , Bronchi/pathology , Bronchial Diseases/diagnosis , Bronchial Diseases/diagnostic imaging , Bronchial Diseases/pathology , Bronchial Diseases/therapy , Bronchoscopy , Female , Humans , Middle Aged , Prognosis , Respiratory Function Tests , Tomography, X-Ray Computed , Trachea/pathology , Tracheal Diseases/diagnosis , Tracheal Diseases/diagnostic imaging , Tracheal Diseases/pathology , Tracheal Diseases/therapy
12.
Hum Immunol ; 63(2): 83-90, 2002 Feb.
Article in English | MEDLINE | ID: mdl-11821155

ABSTRACT

HLA-G is selectively expressed in extravillous trophoblast of human placenta, which does not express classical HLA-A and -B molecules. Several studies report the role of HLA-G as a molecule involved in immune tolerance. By interacting with NK and T cells inhibitory receptors, HLA-G may downregulate their cytotoxicity functions. To appreciate the biologic and clinical relevance of HLA-G expression in lung diseases, HLA class I and HLA-G expression were analyzed in a panel of 36 ex vivo neoplastic tissues and 8 non-neoplastic lung tissues. Immunohistochemical analysis was performed using a pan-HLA class I antibody (W6/32) and three different specific anti-HLA-G antibodies (87G, MEMG/9 and 4H84). These findings demonstrated that HLA-G products were not expressed in pulmonary structural cells. However, HLA-G molecules were detected in activated macrophages and dendritic cells infiltrating lung carcinomas (33%) and nontumoral pulmonary diseases (25%). HLA-G expression was not correlated with classical HLA alterations. No statistical correlation was found between HLA-G expression and clinical or biologic parameters except high tumor size. The expression of HLA-G in myelo-monocytic cells infiltrating lung pathologic tissues could alter antigenic presentation and contribute to decrease immune response efficiency, subsequently favoring the progression of tumoral or inflammatory processes.


Subject(s)
Dendritic Cells/metabolism , Lung Diseases/metabolism , Lung/metabolism , Macrophages/metabolism , Female , HLA Antigens/metabolism , HLA-G Antigens , Histocompatibility Antigens Class I/metabolism , Humans , Lung/cytology , Lung Neoplasms/metabolism , Male
13.
Oncol Rep ; 9(1): 177-80, 2002.
Article in English | MEDLINE | ID: mdl-11748478

ABSTRACT

The monoclonal antibody Po66 is an IgG1 immunoglobulin isolated from a human bronchial squamous carcinoma and directed against a carbohydrate binding protein, Po66-CBP, belonging to the galectin family involved in neoplastic processes. This Po66 antibody has been shown to be useful for immunoscintigraphic detection of squamous cell carcinoma metastasis. We examined the expression of Po66-CBP in a wider range of primary or secondary malignant tumors of the lung of various histological types. We studied 52 specimens of broncho-pulmonary tumors including 41 primary squamous, glandular or neuro-endocrine tumors and 11 secondary tumors of glandular, connective tissue, melanocytic or germinal origin as well as 9 extra-pulmonary primary tumors with histological types similar to lung metastases. An immunohistochemical study was performed using an amplification system on paraffin-embedded sections. All histological types were positive for Po66 antibody, the cell origin giving no influence on the expression of Po66-CBP. There was however a relation between Po66-CBP expression and the degree of differentiation notably for squamous cell cancer and neuro-endocrine tumors. The metastatic character of the tumor tissue did not affect Po66-CBP expression.


Subject(s)
Bronchial Neoplasms/metabolism , Carcinoma/metabolism , Carrier Proteins/metabolism , Galectins , Lectins/metabolism , Lung Neoplasms/metabolism , Adult , Aged , Aged, 80 and over , Bronchial Neoplasms/pathology , Carcinoma/secondary , Female , Humans , Immunoenzyme Techniques , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Metastasis
14.
Leukemia ; 15(11): 1785-91, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11681422

ABSTRACT

The blastic variant (BV) form of mantle cell lymphoma (MCL) is considered to be a very aggressive subtype of non-Hodgkin's lymphoma (NHL). In order to determine its clinico-biological features and response to therapy we studied 33 patients (17%) out of 187 suffering from MCL who were diagnosed with a BV of MCL. Blastic variant was diagnosed according to histopathological patterns, immunophenotyping, and bcl1 gene rearrangement and/or cyclin D1 overexpression. Three patients initially diagnosed with large cell NHL were classified as BV. Patients received front-line therapy including CHOP-like regimen or CVP (n = 29), or chlorambucil (n = 4) and CHOP or ESAP as second-line therapy. High-dose intensification with stem cell transplantation (SCT) was performed in 11 cases (autoSCT, n = 8; alloSCT, n = 3). All but two patients were in complete remission (CR) at the time of transplant (CR1, n = 5; CR2, n = 4). Clinical and biological characteristics did not differ from those of the common form of MCL. The median age was 62 years (29-80), with a sex ratio (M/F) of 2.6:1. Of the 33 patients, 66% had extranodal site involvement, 85% had an Ann Arbor stage IV, and 82% had peripheral lymphadenopathy. Circulating lymphomatous cells were seen in 48% of cases. Twelve patients (36%) entered a CR1 with a median duration of 11 months. Fifteen patients (46%) failed to respond and rapidly died of progressive disease. Second-line therapy led to a 26% (6/23) CR2 rate. Nine patients relapsed after high-dose therapy. Twenty-two of the 33 patients (66%) died of refractory or progressive disease. Median overall survival (OS) time was 14.5 months for the 33 BV patients as compared to 53 months for the 154 patients with a common form of MCL, P <0.0001. In the univariate analysis, OS was influenced by age, extranodal site involvement, circulating lymphomatous cells, and international prognosis index (IPI). In the multivariate analysis, only IPI affected OS: patients with IPI > or =2 had 8 months median OS as compared to 36 months median OS for patients with IPI <2, P = 0.003. Blastic variant is one of the worst forms of NHL. An improved recognition of BV of MCL is required, particularly in high-grade CD5+ NHL using immunophenotyping and bcl1 molecular study. Standard therapy using anthracycline or even high-dose intensification produce poor results and an alternative treatment should be proposed to such patients.


Subject(s)
Lymphoma, Mantle-Cell/diagnosis , Lymphoma, Mantle-Cell/mortality , Adult , Aged , Disease-Free Survival , Female , Gene Rearrangement , Genes, bcl-1 , Humans , Immunophenotyping , Lymphoma, Mantle-Cell/therapy , Male , Middle Aged , Prognosis , Retrospective Studies , Survival Rate , Treatment Outcome
15.
Gastroenterol Clin Biol ; 25(4): 425-8, 2001 Apr.
Article in French | MEDLINE | ID: mdl-11449131

ABSTRACT

We report a case of multiple aseptic splenic abscesses occurring in a woman with Crohn's disease for three years. All microbiological samples were negative. The diagnosis was suspected on abdominal echography and CT scan and confirmed on histologic examination of the splenectomy specimen. The evolution was marked by recurrence of fever and inflammatory syndrome, associated to transitory morphological abnormalities of the accessory spleen. Aseptic splenic abscesses recurrence was suspected. This case allows us to consider aseptic splenic abscesses as an extra-intestinal manifestation and not as a splenic localisation of Crohn's disease.


Subject(s)
Abscess/etiology , Crohn Disease/complications , Splenic Diseases/etiology , Abscess/diagnosis , Adult , Female , Humans , Recurrence , Spleen/pathology , Splenectomy , Splenic Diseases/diagnosis , Splenic Diseases/surgery , Tomography, X-Ray Computed , Ultrasonography
16.
Anticancer Res ; 21(2A): 1049-55, 2001.
Article in English | MEDLINE | ID: mdl-11396139

ABSTRACT

Galectins are animal lectins, which may play a role in neoplastic transformation. Po66-Carbohydrate Binding Protein (Po66-CBP) belongs to the galectin-8 family and is expressed in lung tumor cells but not in normal ones. Recent studies showed that galectin-8 could be used for human lung squamous cell carcinoma radioimmunotherapy. To optimize this method of treatment, we attempted to increase galectin-8 expression in human lung tumor cells. A human lung squamous (SK-MES-1) or adeno (A 549) carcinoma cell line was grown with or without sodium butyrate. Cell growth, morphology, transcriptional, expression translational expression and cellular localization of galectin-8 were studied. 3 mM of sodium butyrate inhibited the two cell lines' growth after 48 hours of treatment, but only in SK-MES-1 cells galectin-8 expression is modulated without any secretion and cellular localization modifications, apoptosis or necrosis. Sodium butyrate could be an interesting tool in optimizing the radioimmunotherapy of human lung squamous carcinoma, but not of adenocarcinoma.


Subject(s)
Butyrates/pharmacology , Galectins , Gene Expression Regulation, Neoplastic/drug effects , Growth Inhibitors/pharmacology , Lectins/genetics , Adenocarcinoma , Animals , Apoptosis , Carcinoma, Squamous Cell , Humans , Lectins/metabolism , Lung Neoplasms , Mice , Necrosis , RNA, Messenger , Tumor Cells, Cultured
17.
Inflamm Res ; 50(3): 129-35, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11339500

ABSTRACT

BACKGROUND: Dysregulation of matrix metalloproteinases (MMPs) has been implicated in lung injury associated with inflammatory disorders and several lung diseases such as pulmonary fibrosis. OBJECTIVE: We studied a murine model of lipopolysaccharide (LPS)-induced chronic inflammation in order to analyse the relationship between MMP activity in bronchoalveolar lavage fluid and collagen deposition in lung tissue. BP2 mice were exposed to repeated aerosols of LPS of E. coli for 8 months. RESULTS: The inflammatory reaction induced by LPS increased throughout the time of exposure and was associated after 10 weeks with collagen deposition in the alveolar walls. Meantime, we observed in BAL fluid from LPS-exposed mice an early induction of MMP-9 correlated with neutrophil recruitment. MMP-2 increased during the early inflammatory phase, and also during the development of the fibrotic phase. CONCLUSION: Repeated exposure of mice to an aerosol of LPS can lead to pulmonary interstitial fibrosis and MMPs seem to be associated with this process.


Subject(s)
Lipopolysaccharides/toxicity , Matrix Metalloproteinase 2/biosynthesis , Matrix Metalloproteinase 9/biosynthesis , Pulmonary Fibrosis/chemically induced , Animals , Collagen/biosynthesis , Lung/pathology , Male , Mice , Pulmonary Fibrosis/metabolism , Pulmonary Fibrosis/pathology
18.
J Pathol ; 193(4): 538-45, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11276015

ABSTRACT

Bleomycin-induced pulmonary fibrosis is known to be associated with the increased activity of two gelatinases, matrix metalloproteinase (MMP)-2 and MMP-9, in bronchoalveolar lavage (BAL). This study has investigated the effect of a synthetic inhibitor of MMP, batimastat, on the development of pulmonary fibrosis induced by bleomycin administration in mice. Animals were intranasally instilled with saline or bleomycin (0.5 mg in 100 microl per mouse). Batimastat (30 mg/kg) or vehicle alone was administered by intraperitoneal injection 24 h and 1 h before saline or bleomycin instillation, and then daily at the same dosage until the end of the study. Fifteen days after bleomycin administration, BAL was performed and the lung was removed. Treatment of mice with batimastat significantly reduced bleomycin-induced lung fibrosis, as shown in the lung by histopathological examination and by a decrease in hydroxyproline levels. Batimastat also prevented the increase in BAL macrophage and lymphocyte numbers, whereas it did not show any effect on the increased expression of active transforming growth factor-beta (TGF-beta) in BAL. Batimastat treatment was effective in reducing MMP-2 and MMP-9 activity as well as the tissue inhibitor of metalloproteinase-1 (TIMP-1) level in BAL. These results suggest that administration of the MMP inhibitor batimastat is useful in preventing experimental pulmonary fibrosis induced by bleomycin and raises the possibility of a therapeutic approach to human pulmonary fibrotic disease.


Subject(s)
Matrix Metalloproteinase Inhibitors , Phenylalanine/analogs & derivatives , Phenylalanine/therapeutic use , Protease Inhibitors/therapeutic use , Pulmonary Fibrosis/prevention & control , Thiophenes/therapeutic use , Animals , Bleomycin , Body Weight/drug effects , Bronchoalveolar Lavage Fluid/cytology , Cell Count , Hydroxyproline/metabolism , Male , Metalloendopeptidases/metabolism , Mice , Mice, Inbred Strains , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/metabolism , Pulmonary Fibrosis/pathology , Survival Rate , Tissue Inhibitor of Metalloproteinases/metabolism
19.
Rev Mal Respir ; 18(5): 541-4, 2001 Oct.
Article in French | MEDLINE | ID: mdl-11887773

ABSTRACT

Pulmonary inflammatory pseudotumors are usually unique lesions of unknown etiology with good prognosis. We report two severe cases with mediastinal invasion, local recurrence, extrathoracic locations, one of them with a fatal evolution. Certain microscopic features, which were present in our cases (increased cellularity, nuclear pleomorphism, mitotic activity, focal necrosis, bizarre giant cells, vascular invasion), may have prognostic relevance in determining an aggressive behavior of these tumors. Surgical resection is the recommended treatment, and incomplete resection, as in our cases, seems to be a risk factor for developing recurrent inflammatory pseudotumor. Immunosuppressive therapy was ineffective as well as radiotherapy in one of our cases. Only high doses of corticosteroids seemed to slow the evolution of the disease.


Subject(s)
Granuloma, Plasma Cell/therapy , Lung Diseases/therapy , Adult , Female , Granuloma, Plasma Cell/pathology , Humans , Lung Diseases/pathology , Male , Middle Aged , Severity of Illness Index
20.
Pathol Res Pract ; 197(12): 797-801, 2001.
Article in English | MEDLINE | ID: mdl-11795826

ABSTRACT

Specified galectins are known to play a role in regulating cell proliferation, differentiation, adhesion and migration. Po66, a mouse IgG1 monoclonal antibody produced by immunization against squamous cell cancer, reacts against a carbohydrate-binding protein (Po66-CBP), recently shown to be a member of the galectin family with a strong homology with galectin-8 (PCTA-1), identified as a human tumor-associated antigen. We studied Po66 in squamous metaplasia of the bronchi in order to determine whether it could be specifically involved in neoplastic conditions and if so, if it would be helpful in distinguishing metaplasia at risk of cancer. Twenty-eight formalin-fixed, paraffin-embedded archival tissues of 17 metaplasias with SCC, 3 metaplasia with distant neoplastic disease and 8 metaplasias with an inflammatory process, were immunostained using a streptavidin biotin peroxydase method. The squamous metaplasias were positively stained in non-neoplastic disease as well as in neoplastic processes. Expression was also observed in stromal and normal cells. Po66-CBP was not associated with a pre-neoplastic character. We discussed the expression of this intra-cellular component of galectin-8 according to the functions of galectins in cellular differentiation, host reaction against tumor, and inflammation.


Subject(s)
Bronchi/metabolism , Carcinoma in Situ/metabolism , Carcinoma, Squamous Cell/metabolism , Galectins , Lectins/metabolism , Lung Diseases, Interstitial/metabolism , Lung Neoplasms/metabolism , Biomarkers, Tumor/metabolism , Bronchi/pathology , Carcinoma in Situ/pathology , Carcinoma, Squamous Cell/pathology , Epithelial Cells/metabolism , Epithelial Cells/pathology , Humans , Immunoenzyme Techniques , Lectins/analysis , Lung Diseases, Interstitial/pathology , Lung Neoplasms/pathology , Metaplasia/metabolism , Metaplasia/pathology
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