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Biomedical subjects

B Brun

Publications and source records attributed to B Brun.

At least 19 recordsLinked to original sources
PubMed2003

[Epstein-Barr virus associated central nervous system leiomyosarcoma occurring after renal transplantation: case report and review of the literature].

Central nervous system leiomyosarcomas are extremely rare, however, they became more frequent among immunodeficient patients, either in a patients infected with human immunodeficiency virus (HIV), or after organ transplantation. The data of the literature indicate that the infection by Epstein-Barr virus (EBV) plays a causal role in the development of these tumours but its precise role in the oncogenesis remains unresolved. We report a new case of EBV associated leiomyosarcoma of the left cavernous sinus occurring after renal transplantation. The epidemiological, clinical, pathological and therapeutic characteristics of these tumours are discussed.

Adult↗
PubMed2002

Cancer: the role of extracellular disease.

Invasive carcinoma originates from the epithelial cells lining the lumen of an organ. It is often preceded by metaplasia, dysplasia or carcinoma in situ. The purpose of this review is to suggest that this disease of the epithelium may be, in part, the result of underlying tissue-based disorganization. Human cancer is frequently associated with pre-existing tissue disease. For example, hepatocellular carcinoma usually occurs in patients with a macronodular cirrhotic liver. Most lung cancers arise among patients with chronic lung disease (bronchitis, emphysema, and chronic infection). Mechanical forces appear to play a major role in regulating normal and cancer cell growth. The loss of cell polarity by neoplastic cells, coupled to an otherwise normal growth rate is enough to explain the cancer star-shaped pattern. By changing the plane of cell division, tumor cells may escape physical constraints from surrounding cells and divide. Loss of cell polarity and the resulting cell proliferation appears to be a consequence of either tissue-based disorganization (chronic inflammation, fibrosis) or of direct carcinogenic insult. The multiple mutations frequently described in cancer may be, in part, secondary to physical stress and not primary events. Several animal and clinical trials have shown that tissue disruption (i.e. radiation-induced fibrosis or liver cirrhosis) can be successfully treated. It is possible that treatment targeted at tissue disruption would delay or reduce cancer incidence regardless of the precise biological mechanism of carcinogenesis.

Adult↗
PubMed2001

Inhibition of fasL sustains phagocytic cells and delays myogenesis in regenerating muscle fibers.

Macrophage-muscle cell interactions are complex, and the majority is unknown. The persistence of inflammatory cells in skeletal muscle could be critical for myofiber viability. In the present paper, we show that FasL plays a role in the resolution of muscle inflammation. We analyzed inflamed muscles of normal mice treated from day 3 to day 8 with a FasL inhibitor (Fas-Ig) or with control Ig. Treated muscles were collected at 3, 5, and 10 days. The treatment with recombinant Fas-Ig protein induced a severe persistence of inflammatory cells at 5 days (115,000+/-27,838 vs. 41,661+/-6848, p<0.01) and 10 days from injury (145,500+/-40,850 vs. 5000+/-1000, p<0.001). Myofiber regeneration was highly impaired (37+/-14 vs. 252+/-28, p<0.01). Apoptosis of phagocytic cells was absent during Fas-Ig treatment (0.9+/-0.6 vs. 1300+/-150, p<0.0001), but apoptotic, mononucleated cells appeared at day 10, 2 days after the suspension of Fas-Ig administration. The time course of FasL expression during muscle inflammation, at mRNA and protein level, reveals a peak during myoblast proliferation. The peak of FasL expression coincides with the peak of apoptosis of phagocytic cells. In situ hybridization shows the co-expression of FasL and MyoD mRNA in mononucleated cells, i.e., myoblasts. Experiments on the myoblast cell culture confirmed the expression of FasL in myoblasts. The findings shown here indicate one of the pathways to control myoblast-macrophage interaction and might be relevant for the control of inflammatory cells in muscle tissue. Perhaps altering FasL expression with recombinant proteins could ameliorate inflammation in degenerative myopathies and up-regulate muscle regeneration.

Animals↗
PubMed2000

[Chemotherapy of metastatic breast cancer].

The most powerful prognostic factor in the treatment of metastatic breast cancer continues to be the response to induction chemotherapy. The range of drugs which are widely used in the treatment of advanced disease, the anthracyclines, the taxanes and vinorelbine, have all shown interesting activity in terms of their ability to obtain both high response rates and long duration of response. The anthracyclines, doxorubicin (DX) and epiadriamycin (EPI) constitute the established reference agents in the treatment of metastatic disease, and combinations of these drugs with vinorelbine (VRB) and the taxanes, paclitaxel (PTX) and docetaxel (DCT), have produced major increases in objective response rates: PTX-DX (58%), DCT-EPI (69.4%), PTX-EPI (71.1%), VRB-DX (75%), VRB-EPI (77.1%). Suggestions for other combinations of chemotherapeutic agents which do not include anthracyclines available with well tolerated and effective drugs. The way forward after a response has been obtained remains an open question in which the limited efficacy of the available drugs and their cumulative toxicity needs to be balanced against the quality of life of patients during their disease. Defining the optimal strategy for the management of disease after induction treatment is a problem which needs to draw on the results of research, analysis of experience and insight into the needs of patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Apoptosis of myofibres and satellite cells: exercise-induced damage in skeletal muscle of the mouse.

Apoptosis is well accepted as a type of cell death occurring in the development of mammalian muscles, but the death of adult myofibres in neuromuscular disorders and exercise-induced muscle damage is usually explained in terms of muscle necrosis. The current view that apoptosis precedes necrosis in death of dystrophin-deficient muscle fibres of mdx mouse has been well substantiated. Moreover, apoptotic myonuclei have been reported to increase in mdx mice 2 days after spontaneous exercise. To investigate the contribution of apoptosis to exercise-induced damage of normal muscle fibre a time-course analysis has been performed in adult C57BL/6 mice. Groups of five mice were sacrificed immediately after the end of the exercise, and after a rest period of 6 or 96 h. The amount of apoptosis in leg muscles was assessed by electron microscopy, by the terminal deoxynucleotidyl transferase assay and by electrophoretic detection of fragmented DNA; the expression of Bcl-2, Bax, Fas, ICE, p53 and ubiquitin was examined by immunohistochemistry and Western blot. Absent in muscles of normal 'sedentary' mice, apoptotic myonuclei peak in muscles of normal mice after a night of spontaneous wheel-running (4% +/- 3.5, immediately and 2.5% +/- 1.8 after 6 h rest, P < 0.05 vs non-runner mice); they then decrease but are present 4 days later (0.8% +/- 1.5). Satellite cells are also involved in the apoptotic process. Myofibre content of Bcl-2 decreases whereas Bax, Fas, ICE and ubiquitin modify their pattern of expression in correlation with the changes in apoptotic myonuclei. Apoptosis of endothelial cells is present after the night of wheel-running and with a twofold increase 4 days later (1.5 +/- 2.3 and 4.8 +/- 4.4 P < 0.05, respectively). Satellite cells are also involved in the apoptotic process. Thus, spontaneous running in unaccustomed mice increases the number of apoptotic nuclei in adult muscle fibres and in endothelial cells. It remains to be established whether muscle apoptosis is restricted to the repair mechanisms, as often suggested in many pathologic processes, or it is also part of pathogenesis of muscle damage. Regardless of whether these results are extended to human dystrophies, the clinical implications in terms of secondary pathogenetic mechanisms and muscle training are obvious.

Animals↗
PubMed1997

Response to second-line chemotherapy in patients with metastatic breast carcinoma previously responsive to first-line treatment: prognostic factors.

BACKGROUND: The aim of this retrospective study was to determine those prognostic factors associated with response to a second-line chemotherapy in patients with metastatic breast carcinoma (MBC) that was previously responsive to a first-line chemotherapy. METHODS: The 70 MBC patients studied had previously responded to a first-line chemotherapy, mainly anthracycline or anthracenedione-containing regimens. During first-line chemotherapy they had received treatment until the maximum response was obtained, at which time treatment was discontinued. Second-line chemotherapy regimens were of several types (48.5% with anthracycline). A study of prognostic factors associated with response to second-line chemotherapy was performed by univariate and multivariate analysis. RESULTS: Second-line chemotherapy achieved a 44% response rate, with a median response duration of 10 months. Survival was 13 months in the entire patient group, 22 months in responders, and 8 months in nonresponders. Univariate analysis identified seven factors related to patient response rate to second-line treatment. A better response rate to second-line chemotherapy was observed in patients with the following features: 1) chemotherapy free time (time between onset of metastatic disease and initiation of first-line) < 12 months (P = 0.03); 2) complete response to first-line chemotherapy (P = 0.013); 3) response duration to first-line chemotherapy > 14 months (P = 0.0001); 4) progression free interval (time between end of first-line treatment and initiation of second-line chemotherapy) > 11 months (P = 0.0001); 5) performance status at second-line treatment < 2 (P = 0.04); 6) tumor index at second-line chemotherapy < 4 (P = 0.05); and 7) treatment with an anthracycline-containing second-line regimen (P = 0.03). In multivariate analysis, only progression free interval was identified as being associated with response rate to second-line chemotherapy (P = 0.0001). CONCLUSIONS: Retained chemosensitivity appeared to be an important characteristic in patients responding to second-line chemotherapy.

Adult↗
PubMed1997

Meiotic study of hybrids in the genus Eulemur and taxonomic considerations.

A reproductive study was conducted on seven hybrids of Eulemur showing chromosomal multivalents involving at least four chromosomes at the pachytene stage. Three individuals were infertile hybrids and one presented a reduced spermatogenesis. In three out of these four hybrids, multivalents were associated with the sex bivalent in a large number of spermatocytes (23%). The relative importance of the reduction of fertility in males linked to chromosomal multivalent formation as well as the genetic background is discussed with regard to the use of cytogenetic data for systematics. Our findings argue for the classification of Eulemur fulvus collaris and E. f. albocollaris in two separate species. In regard to their repartition area, their separation along a linear north-south axis in Madagascar is discussed.

Abortion, Veterinary↗
PubMed1997

Prognostic factors in patients with localized Ewing's sarcoma: the effect on survival of actual received drug dose intensity and of histologic response to induction therapy.

To bring to the fore the most important prognostic factors in Ewing's sarcoma (ES) with current protocols, we studied the classical prognostic factors, dose intensity (DI) of actual received drugs, age and histological response to induction therapy and their correlation in 39 patients with localized ES treated from 11/85 to 06/95 to identify eventual predictors of event-free survival (EFS). Inclusion criteria were age 35 yr or less, definitive local treatment by our team and chemotherapy including at least 4 drugs: vincristine (VCR), dactinomycin (DACT), doxorubicin (DOXO) cyclophosphamide (CPX). The endpoint was the absence of relapse. Parameters related to the status of patients were tested using the Chi square test or Fisher's exact test. The non parametric Kruskal-Wallis test was used for quantitative data. When necessary stratified analysis was done using the Mantel Cox test. With a median follow-up of 7 yr, overall survival (OS) and EFS were both 67% at 7 yr. According to univariate analysis, the significant predictors of survival were the DI of VCR and DACT, the histological response to preoperative chemotherapy (CT), the patient's age (< 18 yr DFS: 84%; > 18 yr DFS: 38%). The risk of metastases was almost tenfold higher in patients with low received DI of VCR (DFS 40% versus 95%) and of DACT (DFS 48% versus 94%). The prognostic value of primary tumor characteristics (tumoral volume or location) was erased by the comprehensive treatment. Following multivariate analysis, the actual received DI of VCR (p < 0.02) and DACT (p < 0.03) and the histological response to preoperative CT (p < 0.05) were retained as the only significant independent predictors of EFS. Taking into account the actual received DI of VCR and DACT, the prognostic value of age disappears. In conclusion, this study points out the main role of the drug DI in ES (particularly VCR and DACT) and of histological response to preoperative CT.

Adolescent↗
PubMed1996

[Psychological theories in relation to the development of schizophrenia].

A description of schizophrenia is given from a psychodynamic perspective. The illness is subsequently illuminated by means of different psychological theories, as the characteristic symptomatology is explained through five basic branches of psychology: The psychology of perception, motivation, cognition, personality formation and developmental psychology. Finally, current treatment-strategies are discussed.

Humans↗
PubMed1996

Erdheim-Chester disease. Clinical and radiologic characteristics of 59 cases.

We made a retrospective evaluation of clinical and radiologic features, treatment, and outcome of Erdheim-Chester disease, a rare non-Langerhans cell histiocytosis. We had 7 patients coming from 3 French teaching hospitals and reviewed 52 cases from the literature. These cases were considered to have Erdheim-Chester disease when they had either typical bone radiographs (symmetrical long bones osteosclerosis) and/or histologic criteria disclosing histiocytic infiltration without features for Langerhans cell histiocytosis (no S-100 protein, no intracytoplasmic Birbeck granules). Ages at diagnosis ranged from 7 to 84 years (mean +/- SD = 53 +/- 14 yr) with a male/female ratio of 33/26. Bone pain was the most frequent clinical sign (28/59), mostly located in the lower limbs. Exophthalmos and diabetes insipidus were found in respectively 16/59 and 17/59 patients. General symptoms (fever, weight loss) and "xanthomas" (mainly located on the eyelids) were present in 11/59 patients. Retroperitoneal involvement was found in 17/59 patients. Skeletal X-ray showed typical osteosclerosis of the diaphysis of the long bones in 45/59 patients. Bone radiographs showed osteolytic lesions of the flat bones (skull, ribs) in 8 patients. Histologic diagnosis was performed after a bone biopsy (28 patients), a retroorbital biopsy (9 patients), and/or a biopsy of the retroperitoneal infiltration or the kidney (11 patients). Six of our 7 patients but only 5 of 52 patients from the literature had the complete histologic criteria, disclosing no Birbeck granules or S-100 immunostaining. In other cases, histologic results usually described a xanthogranulomatous infiltration by foamy histiocytes nested in fibrosis. Treatment was corticotherapy (20/59), chemotherapy (8/59), radiotherapy (6/59), surgery (3/59) and immunotherapy (1 patient). Twenty-two patients died after a mean follow-up of 32 +/- 30 mo (range, 3-120 mo). In conclusion, Erdheim-Chester disease may be confused with Langerhans cell histiocytosis as it sometimes shares the same clinical (exophthalmos, diabetes insipidus) or radiologic (osteolytic lesions) findings. However, it also appears to have distinctive features. Patients are older and have a worse prognosis than those with Langerhans cell histiocytosis, and the diagnosis relies on the association of specific radiologic and histologic findings.

Adolescent↗
PubMed1996

[Comparison of concomitant radiotherapy and chemotherapy with radiotherapy alone in advanced cancers of the head and neck: results of a randomized trial].

From April 1987 to October 1992, 67 patients with inoperable squamous cell carcinoma of the head and neck region were included in a randomized trial. All patients had induction chemotherapy with cisplatin (100 mg/m2, D1) and fluorouracil (1 g/m2, from D1 to D5) every three weeks for a total of three cycles. Patients were randomized to concurrent external radiation therapy (70 Gy/39 fractions/8 weeks) and chemotherapy with cisplatin (50 mg/m2 in short infusion, D1, D15, D29, D43) and fluorouracil (5 mg/kg, intra-muscular, every Monday, Wednesday and Friday) (experimental group) versus radiotherapy alone with the same modalities (control group). The followup for living patients was 14 to 60 months with a median of 42 months. Analysis of preliminary results has shown that: 1) early and late side effects are similar in both groups; 2) after completion of treatment, the percentage of patients in complete remission was 71% (20/28) in the experimental group and 43% (12/28) in the control group; this difference was statistically significant among non responders to induction chemotherapy (1/15 versus 13/20, P = 0.001), but non significant among responders (11/13 versus 7/8) and 3) there were no differences between both randomized groups in term of 3-year overall survival and of 3-year loco-regional control. Results are discussed taking into account a review of literature.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Management of breast cancer in the elderly.

The management of breast cancer in elderly women was analysed by a retrospective study of 150 women over 70 years old referred to our department between 1984 and 1988. 80 were T1-T2, 33 were T3 and 34 were T4. 107 were N0 and 43 were N1-N2. 16 women (11%) were in poor health, preventing conventional treatment. Treatment choice varied with age: 60% of the women aged 70-79 (group 1) and 23% of the oldest women (group 2) were treated conventionally. The use of surgery decreased with age and surgical procedures were conventional in only 85% of the group 1 women and in 56% of the group 2 women. Definitive radiation therapy was used more frequently in the oldest women, as was primary hormone therapy. Quality of follow-up also varied with age. Five-year survival rates were still high in both groups while relapses were frequent. Breast cancer was consequently a frequent cause of death. The increase in the proportion of elderly people with breast cancers over the next few years will require validated guidelines. Specific protocols and specific rules of management must be drawn up.

Age Factors↗
PubMed1991

External irradiation prior to conservative surgery for breast cancer treatment.

From 1981 to 1987, 138 patients with breast cancer unsuitable for primary tumorectomy received initial external radiotherapy (45 Gy/25f/35d) in order to reduce the tumor volume so that secondary limited surgery could be performed. There were 81 T2 and 57 T3. Fifty-seven percent of the patients had a tumor larger than 4.5 cm. After completion of the radiotherapy, 22 patients (16%) showed no more evidence of a tumor either clinically or radiologically and received a boost of 25 Gy. In 52 cases (38%) the tumor regression allowed for secondary tumorectomy followed by a boost of 20 Gy. Sixty-four patients (46%) showed either little or no tumor regression: radical surgery was performed in 14 cases (10%) and high dose boost curietherapy (37 Gy) in the 50 (36%) remaining patients who refused mastectomy. Breast conservation in good condition was thus obtained in 74 patients (54%). Sufficient tumor regression to allow secondary tumorectomy was more often observed in T2 than in T3, in poorly differentiated tumors or mucinous type, and in tumor with well defined mammographic aspects. Actuarial 5-year local control and disease-free survival rates after limited surgery were, respectively, 90% and 73%. No particular complications were observed after secondary tumorectomy. This therapeutic approach is encouraging in patients with large T2 and T3 breast tumors, but a longer follow-up is required to assess definitive conclusions.

Breast Neoplasms↗