Exposure to genotoxic agents, host factors, and lifestyle influence the number of centromeric signals in micronuclei: a pooled re-analysis.

We pooled data from three biomonitoring studies using the cytokinesis-block micronucleus assay in peripheral blood lymphocytes in combination with fluorescence in situ hybridization. Centromere-positive micronuclei (C+MN) were classified in two groups: those containing one centromere (C1+MN) and those with two or more (Cx+MN). The three studies evaluated untreated cancer patients, welders, and pathologists/anatomists exposed to formaldehyde. The total number of subjects included in the pooled re-analysis was 113. A higher frequency of C+MN was observed in cancer patients and exposed workers, who showed significant differences from controls in all studies. C1+MN were particularly increased in the group of pathologists/anatomists, who showed a 3.29 times higher frequency than controls (95% CI: 2.04-5.30). A borderline increase in Cx+MN was observed in welders when compared to the corresponding control group (FR: 1.31; 95% CI: 0.99-1.74). An evident effect of gender was found, with significantly increased frequencies of all endpoints measuring aneuploidy in females (C+MN, C1+MN, and Cx+MN). Alcohol consumption had a significant effect on total MN frequency and particularly on C+MN and C1+MN. In conclusion, scoring the number of centromeric signals in the micronucleus assay provides additional information about the mechanism of action of various genotoxic agents, and the role of confounding factors may be more specifically accounted for. Indeed, C+MN could be efficiently used in biomonitoring studies as an independent biomarker of exposure and early biological effect. The use of centromeric signals allows the identification of two further endpoints, representing two alternative pathways of chromosome loss, i.e., impaired chromosome migration, leading to increased C1+MN frequency, and centrosome amplification, possibly leading to Cx+MN with two or more centromeric signals.

Recurrences following primary osteosarcoma in adolescents and adults previously treated with chemotherapy.

In this retrospective analysis, we report on the detailed management of 33 recurrent osteosarcoma patients from a population of 81 adolescents and adults previously treated (between November 1979 and November 1998) at the La Timone Adults Hospital, for an extremity-localised osteosarcoma. The site of the first recurrence was limited to the lung in 24 patients (73%), was local in 4 patients (12%), at multiple sites in 4 patients (12%), and limited to the bone for 1 patient (3%). The median interval between the diagnosis of the primary osteosarcoma and the first recurrence was 16 months (range 4-108 months). For all patients, the treatment combined aggressive chemotherapy and surgical resection of the recurrences whenever possible. 19 patients (58%) achieved a second complete remission. The median follow-up time from the first recurrence was 18 months (range 4-150 months). For all patients, the median overall survival from first recurrence was 17 months (95% confidence interval (CI), 11-22 months) and the projected 3- and 5-year survival rates were 31.6 and 23.7%, respectively. Patients with a second complete remission had a better 5-year survival than patients without (44.6% versus 0%, P=0.001). The achievement of a second complete remission has an independent significant prognostic value for an improved survival. Aggressive surgery with the removal of recurrence sites combined with multi-agent chemotherapy can either cure patients with recurrent osteosarcoma or significantly prolong their survival.

Acentromeric micronuclei are increased in peripheral blood lymphocytes of untreated cancer patients.

Increased micronucleated cell rates, dicentric chromosomes, and other chromosomal damages have been reported in lymphocytes of cancer patients prior to the initiation of chemotherapy, and/or radiotherapy. The cause of these chromosomal damages in these lymphocytes remains unclear. In the present work, we investigated whether these micronuclei mainly reflect structural or numerical chromosomal aberrations by applying the cytokinesis-blocked micronucleus (CBMN) assay in combination with fluorescent in situ hybridization (FISH) of a DNA centromeric probe on blood samples of 10 untreated cancer patients (UCPs), and 10 healthy subjects (HSs). Micronucleated binucleated lymphocyte rate was significantly increased in patients (mean+/-S.D.: 19.0 per thousand +/-14.1 versus 9.2 per thousand +/-4.6 in controls). Trinucleated cytokinesis-blocked cells were not significantly higher in patients than in controls. Acentromeric, centromeric, and multicentromeric micronucleus levels were two-fold higher in patients than in controls, but the difference was significant only with acentromeric micronuclei. The percentage of micronuclei containing one or more centromeres averaged 69.2, and 71.5% in patients, and controls, respectively. The percentage of micronuclei containing several centromeres was 44.7% in patients, and 54.6% in controls. Among centromere-positive micronuclei, the percentage of micronuclei containing several centromeres averaged 59.7% in patients, and 75.4% in controls. These results indicate that genetic instability in peripheral blood lymphocytes of UCPs occurs because of enhanced chromosome breakage. However, a substantial proportion of this genetic instability occurs because of defects in chromosome segregation.

[Nutritional workshops for cancer patients: a pilot approach]. / Les ateliers de nutrition en oncologie médicale: une expérience pilote.

The authors describe an original experience with 3 years of a nutritional workshop for cancer patients. This intervention combine an information about nutritional aspects of cancer with psychosocial support, to buffer psychological and nutritional consequences of cancer. The workshop, leaded by two specialized teams, one in medical oncology, the other in public health, is proposed to patients during and after a specific treatment. In one day, it provided information about nutrition and cancer, diet education and psychosocial support with supportive-expressive group. At this day, the evaluation of this intervention is only subjective. Fifty-six patients participated in at least one workshop, with majority of women (91%). Nineteen workshops were leaded with average participant number of 7 per workshop the third year. The authors believe that nutritional workshops are of great help for cancer patients, by enhancing social reinsertion, giving opportunity of emotional expression and humanizing the treatment. Our experience show it is possible to propose psychosocial intervention in institution in the context of Mediterranean country. We are leading currently a study that will permit a more systematic evaluation of the effects of this intervention.

[Doxorubicin and cisplatin genotoxicity: search for a real indication using the micronucleus test]. / Génotoxicité de la doxorubicine et du cisplatine: recherche d'un témoin positif pour le test des micronoyaux.

Doxorubicin and cisplatin are two major anticancer drugs, and are also known to be mutagen. Using short term mutagenesis tests, the cytokinesis-block micronucleus test and chromosome aberrations test, a study of the cytotoxicity and the mutagenicity of these two drugs has been aimed to determine a genotoxic of reference for these tests. Cisplatin and doxorubicin were genotoxic and gave positive results with the two tests. Since cisplatin was more cytotoxic than doxorubicin for a same genotoxicity, doxorubicin has been selected as a positive control for these two short-term mutagenesis tests. A study of the individual variability in the response to in vitro doxorubicin exposure was made using the cytokinesis-block micronucleus test, applied to cultured T lymphocytes form healthy subjects and cancer patients. Micronucleated cell rate before (T0) and after in vitro exposure to doxorubicin (T1) were determined in the two groups of subjects. Micronucleated cell rates T1 were significantly higher than T0 for healthy subjects and cancer patients. A calculated sensitivity index [(T1)-(T0)] is proposed to evaluate the individual sensitivity to the positive control doxorubicin.

[Chondrosarcoma in nasal fossae and Maffucci's syndrome]. / Chondrosarcome des fosses nasales et syndrome de Maffucci-Kast.

INTRODUCTION: Maffucci's syndrome is a congenital non-hereditary disease very similar to Ollier's disease and associates multiple cutaneous hemangiomas, dyschondroplasia and often enchondromas. EXEGESIS: We report a unique case involving synchronous localization of chondrosarcoma in nasal fossae and anterior chest wall, disclosing Maffucci's syndrome. CONCLUSION: Atypical chondrosarcoma localization must lead to further investigation of potential multiple enchondromatosis.

Osteosarcomas of flat bones in adolescents and adults.

BACKGROUND: Osteosarcomas typically are long bone tumors and rarely affect the flat bones of the axial or appendicular skeleton. METHODS: The authors examined cases of high grade osteosarcoma of flat bones diagnosed at La Timone Adults University Hospital during a 16-year period. RESULTS: Sixteen patients with flat bone osteosarcomas were treated between 1980-1997. The median age of the patients was 25 years, with a male-to-female ratio of 14:2. Common presenting symptoms were swelling, pain, or both. Primary therapy included resection (n = 11 patients: alone in 8 patients and with radiation therapy in 3 patients), radiation therapy (n = 2 patients), or no local treatment (n = 3 patients). All patients received polychemotherapy, 7 preoperatively and postoperatively and 9 in the adjuvant setting. The overall 5-year survival rate was 47.7%; the overall median survival was 39 months (range, 4-211 months). The adequate local control rate was 68.7%. The local recurrence rate in patients who benefited from local treatment was 54%. Significant adverse prognostic factors on survival included the presence of synchronous metastases (three patients), metastases at any time during the course of the disease (eight patients), and inadequate local control (five patients). The overriding predictor of survival appeared to be the presence of metastases. Local recurrence appeared to have no influence on survival. No patient with metastases was alive at 3 years, whereas patients without recurrence or with local recurrence alone had a 5-year survival rate of 100%. Because the majority of patients with flat bone osteosarcomas ultimately die of metastatic disease, intensive systematic polychemotherapy should be an important component of treating these tumors. CONCLUSIONS: Based on the very encouraging results observed in the treatment of long bone osteosarcomas, the therapy for flat bone osteosarcomas should combine radical surgery with preoperative and postoperative adjuvant chemotherapy.