Biomedical subjects

Jacques Bosq

Publications and source records attributed to Jacques Bosq.

10 recordsLinked to original sources

PubMed2006

Expression of the granzyme B inhibitor PI9 predicts outcome in nasal NK/T-cell lymphoma: results of a Western series of 48 patients treated with first-line polychemotherapy within the Groupe d'Etude des Lymphomes de l'Adulte (GELA) trials.

Nasal NK/T-cell lymphoma is a rare disease entity with a poor outcome. Expression of antiapoptotic proteins has not been extensively investigated in this entity. Forty-eight patients with nasal T/NK-cell lymphoma who received first-line polychemotherapy (n = 44) or chemoradiotherapy (n = 4) were analyzed for expression of active caspase-3 (aC3), granzyme B protease inhibitor 9 (PI9), and Bcl-2 proteins. Lymphomas were CD3+/CD5-/granzyme B+ and EBV-associated. Median age was 46 years. Stage I/II disease was present in 75% of the cases and an International Prognostic Index (IPI) score less than 1 in 65%. With a median follow-up of 6.3 years, 5-year event-free survival (EFS) and overall survival (OS) rates were 39% and 49%, respectively. Apoptotic index was scored as high in 32% of cases and PI9 expression as positive in 68%, whereas 35% disclosed a high number of aC3+ tumor cells. Univariate analysis showed that absence of PI9 and low apoptotic index were associated with poor outcome, but not aC3 expression nor IPI score. By multivariate analysis, both parameters affected independently EFS (P = .02 and .08, respectively) and OS (P = .009 and .04). In view of its constitutive expression by normal NK cells, it is suggested that loss of PI9 expression in tumor cells may reflect some mechanism associated with progression.

Adult↗

PubMed2006

Combined-modality therapy for clinical stage I or II Hodgkin's lymphoma: long-term results of the European Organisation for Research and Treatment of Cancer H7 randomized controlled trials.

PURPOSE: In early-stage Hodgkin's lymphoma (HL), subtotal nodal irradiation (STNI) and combined chemotherapy/radiotherapy produce high disease control rates but also considerable late toxicity. The aim of this study was to reduce this toxicity using a combination of low-intensity chemotherapy and involved-field radiotherapy (IF-RT) without jeopardizing disease control. PATIENTS AND METHODS: Patients with stage I or II HL were stratified into two groups, favorable and unfavorable, based on the following four prognostic factors: age, symptoms, number of involved areas, and mediastinal-thoracic ratio. The experimental therapy consisted of six cycles of epirubicin, bleomycin, vinblastine, and prednisone (EBVP) followed by IF-RT. It was randomly compared, in favorable patients, to STNI and, in unfavorable patients, to six cycles of mechlorethamine, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, and vinblastine (MOPP/ABV hybrid) and IF-RT. RESULTS: Median follow-up time of the 722 patients included was 9 years. In 333 favorable patients, the 10-year event-free survival rates (EFS) were 88% in the EBVP arm and 78% in the STNI arm (P = .0113), with similar 10-year overall survival (OS) rates (92% v 92%, respectively; P = .79). In 389 unfavorable patients, the 10-year EFS rate was 88% in the MOPP/ABV arm compared with 68% in the EBVP arm (P < .001), leading to 10-year OS rates of 87% and 79%, respectively (P = .0175). CONCLUSION: A treatment strategy for early-stage HL based on prognostic factors leads to high OS rates in both favorable and unfavorable patients. In favorable patients, the combination of EBVP and IF-RT can replace STNI as standard treatment. In unfavorable patients, EBVP is significantly less efficient than MOPP/ABV.

Adolescent↗

PubMed2005

In nasopharyngeal carcinoma cells, Epstein-Barr virus LMP1 interacts with galectin 9 in membrane raft elements resistant to simvastatin.

Nasopharyngeal carcinomas (NPC) are etiologically related to the Epstein-Barr virus (EBV), and malignant NPC cells have consistent although heterogeneous expression of the EBV latent membrane protein 1 (LMP1). LMP1 trafficking and signaling require its incorporation into membrane rafts. Conversely, raft environment is likely to modulate LMP1 activity. In order to investigate NPC-specific raft partners of LMP1, rafts derived from the C15 NPC xenograft were submitted to preparative immunoprecipitation of LMP1 combined with mass spectrometry analysis of coimmunoprecipitated proteins. Through this procedure, galectin 9, a beta-galactoside binding lectin and Hodgkin tumor antigen, was identified as a novel LMP1 partner. LMP1 interaction with galectin 9 was confirmed by coimmunoprecipitation and Western blotting in whole-cell extracts of NPC and EBV-transformed B cells (lymphoblastoid cell lines [LCLs]). Using mutant proteins expressed in HeLa cells, LMP1 was shown to bind galectin 9 in a TRAF3-independent manner. Galectin 9 is abundant in NPC biopsies as well as in LCLs, whereas it is absent in Burkitt lymphoma cells. In subsequent experiments, NPC cells were treated with Simvastatin, a drug reported to dissociate LMP1 from membrane rafts in EBV-transformed B cells. We found no significant effects of Simvastatin on the distribution of LMP1 and galectin 9 in NPC cell rafts. However, Simvastatin was highly cytotoxic for NPC cells, regardless of the presence or absence of LMP1. This suggests that Simvastatin is a potentially useful agent for the treatment of NPCs although it has distinct mechanisms of action in NPC and LCL cells.

Blotting, Western↗

PubMed2005

Blastic NK-cell lymphomas (agranular CD4+CD56+ hematodermic neoplasms): a review.

Blastic natural killer (NK) cell lymphoma (also termed CD4+CD56+ hematodermic neoplasm) is a recently described entity, with the first case reported in 1994. It was suggested initially that the disease originates from NK cells. Since 1994, single cases and a few small series have been published. In this review, data from the literature and a series of 30 cases from the French and Dutch study groups on cutaneous lymphomas are discussed. The major clinical, histopathologic, and phenotypic aspects of the disease and diagnostic criteria and data suggesting a plasmacytoid dendritic cell origin for the tumor cells are provided.

Adult↗

PubMed2004

Tetranucleotide microsatellite instability in surgical margins for prediction of local recurrence of head and neck squamous cell carcinoma.

PURPOSE: Postoperative radiotherapy is used to prevent local recurrence of head and neck squamous cell carcinoma in patients with positive surgical margins. We sought to determine whether tetranucleotide microsatellite instability could be detected in surgical margins and used to predict local recurrence. EXPERIMENTAL DESIGN: We prospectively collected tumor and surgical margin specimens from patients with head and neck squamous cell carcinoma who had undergone surgical resection at Institut Gustave-Roussy during a 1-year period. Margins were considered positive if extensive pathological examination revealed either carcinoma within 5 mm or dysplasia. We tested five tetranucleotide microsatellite markers (UT5085, L17686, D9S753, ACTBP2, and CSF1R) in the tumor specimens and paired surgical margins of the patients whose margins were negative on pathological examination. RESULTS: Pathological examination revealed that among the 76 patients, 22 had positive margins; therefore, these patients were excluded. Of the 54 remaining patients, 26 (48%) had tumors informative for markers UT5085, L17686, or both; the other 3 markers were not informative. Seven (27%) of the 26 informative tumors had the same instability pattern in the surgical margins. At a median follow-up of 26 months, 5 of the 7 local recurrences occurred in patients with molecularly positive surgical margins. A strong, independent association was found between positive surgical margins and local recurrence (P = 0.01; hazard ratio, 6.49). CONCLUSIONS: Tetranucleotide microsatellite instability in surgical margins may be a useful biomarker to predict local recurrence of head and neck squamous cell carcinoma in patients with apparently disease-free margins.

Adult↗

PubMed2004

High level of glutathione-S-transferase pi expression in mantle cell lymphomas.

PURPOSE: Prognosis of mantle cell lymphoma (MCL) remains poor. Patients who achieve a response to first line therapy usually relapse, and the probability of cure remains low. Glutathione-S-transferase pi (GST-pi) overexpression has been associated with alkylating agents and anthracycline resistance. GST-pi gene is located in 11q13 and is coamplified along with CCND1 gene in some human solid tumors. EXPERIMENTAL DESIGN: We performed immunohistochemical analysis of GST-pi expression in 24 consecutive MCLs, 12 follicular lymphomas (FLs), and 69 diffuse large B-cell lymphomas (DLBCLs). Cases were classified in three groups: high GST-pi expression (> 50% of cells were stained), moderate (5 to 50% cells were stained), or absent (< 5% cells were stained). GST-pi and CCND1 mRNA levels were also assessed by real-time reverse transcription-PCR analysis. RESULTS: All MCLs exhibit high GST-pi protein expression, compared with 29% of the DLBCLs and none of the FLs. MCLs expressed high levels of GST-pi and CCND1 mRNAs compared with DLBCLs and FLs. There was a strong relation between GST-pi and CCND1 mRNAs transcript levels in MCLs but not in DLBCLs. In conclusion, protein and mRNA GST-pi expression is high in MCL compared with FL and DLBCL. CONCLUSIONS: Overexpression of CCND1 in MCL is associated with a transcriptional up-regulation of the GST-pi gene. Our results suggest that the glutathione system could play a role in drug resistance in MCL.

Adult↗

PubMed2004

[Hematodermic CD4/CD56 neoplasm].

Hematodermic CD4/CD56 neoplasm is a recently described entity. This name has been initially proposed by the French Study Group on Cutaneous Lymphomas which established the primary anatomoclinical and pathogenic and cytogenic bases of the disease in 1999. This descriptive and provisional name allowed conceptualizing the entity by its main clinical and phenotypical characteristics. The first case in the literature goes back to 1994. Since that time, several other cases have been published. The expression of CD56 led most of the authors to propose an NK-cell lineage origin. In the last WHO classification of lymphomas, the entity was indexed under the name of "blastic NK-cell lymphoma". However, the authors underlined that there were currently no clues to the etiology of blastic NK-cell lymphoma and that the precise lineage of this disease was still unresolved. At the clinical level the main characteristics of the disease are the skin tropism and the occurrence of a leukemic phase at any time during the course of the disease. The median age is 59 but pediatric cases do exist. At the morphological level skin biopsy shows a monomorphous cell proliferation simulating a pleomorphic T cell cutaneous lymphoma. The diagnosis is based on phenotypic criteria which require frozen tissue. Currently, the main characteristics are the expression of CD4 and CD56 antigens while the main defined lineage specific markers are negative (B-cell, T-cell, NK-cell and myeloid-cell lineages). The origin of the tumor cells still remains uncertain but the plasmacytoid dendritic cell is presently a very serious candidate. The tumor cells share a great phenotypical homology and particularly the expression of the CD123 antigen. Functional homologies have also been demonstrated with tumor cells in vitro. Outcome of CD4/CD56 hematodermic neoplasms is very bad. The median time of survival is 14 months irrespective of the treatment given. Conventional chemotherapies used for the treatment of aggressive lymphomas or acute myeloid leukemias are quickly inefficient.

Adolescent↗

PubMed2003

[Expression of epidermal growth factor receptor and its ligands in other malignant tumor pathologies].

The aim of this review was to describe expression of epithelial growth factor receptor (EGFR) and of its ligands in a panel of tumours (which are not specified elsewhere in this special issue of Bulletin du Cancer): squamous cell carcinomas, adenocarcinomas, sarcomas, brain and germ line tumours. The role of EGFR and its ligands in the carcinogenesis and the progression of these tumours, as well as the relevance of targeting EGFR.

Adenocarcinoma↗

PubMed2002

Hodgkin's disease primarily involving the oropharynx: case report and review of the literature.

We report a rare case of Hodgkin's disease primarily involving the oropharyngeal region. The patient presented with stage IIEA disease with a favorable response to treatment. Our literature search revealed that this disease affected rarely the lymphoid tissues of Waldeyer's ring. In this atypical location, tonsil and nasopharynx represent the most frequently involved sites. The involvement of the posterior wall of the oropharynx by Hodgkin's disease has been reported only once so far. When Waldeyer's ring is involved, the disease is usually localized, with occasional involvement of cervical lymph nodes. In this location, mixed cellularity is the most frequent histologic subtype and the Epstein-Barr virus is found in the majority of cases. This report is followed by a discussion on the clinical and pathological features, the implication of Epstein-Barrs virus and a literature review for Hodgkin's disease involving Waldeyer's ring.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2002

[Multifocal nodular oncocytic hyperplasia of the parotid: case report].

Multifocal nodular oncocytic hyperplasia of salivary glands is a tumor-like lesion that occurs predominantly in the parotid gland. The differential diagnosis of the clear cell variant includes many malignant salivary gland tumors. We report the case of a 66-year-old woman who was referred for a left total parotidectomy allowing the final diagnosis of clear cell multifocal nodular oncocytic hyperplasia. The differential diagnoses and histopathogenesis of this rare entity are discussed.

Adenoma, Oxyphilic↗