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1. Response of chemosensitive and chemoresistant leukemic cell lines to drug therapy: Simultaneous assessment of proliferation, apoptosis, and necrosis

Author

M. Mousseau, M. Barbier, Xavier Ronot, Jean Boutonnat, K. A. Muirhead, D. Seigneurin, and Didier Grunwald

Subjects
Programmed cell death, Cell division, medicine.diagnostic_test, Cell growth, Cell, Biophysics, Cell Biology, Hematology, Biology, Cell cycle, Pathology and Forensic Medicine, Cell biology, Flow cytometry, chemistry.chemical_compound, Endocrinology, medicine.anatomical_structure, chemistry, medicine, Propidium iodide, Cytometry
Abstract

Background: The balance between cell proliferation and drug-induced cell death by apoptosis or necrosis plays a major role in determining response to chemotherapy. Commonly-used DNA analysis methods cannot study both parameters simultaneously. A new approach described here combines a green fluorescent membrane-intercalating dye (PKH67) with Hoechst 33342 or annexin V and propidium iodide, to allow simultaneous assessment of cell division, cell cycle status, apoptosis, and necrosis, respectively. Methods: To test this approach, we used cultured K562 leukemic cell lines which are drug-sensitive (K562S) or drug-resistant (K562R) by virtue of whether they lack or exhibit expression, respectively, of the gp-170 (PGP) glycoprotein pump involved in multidrug resistance. Results: We found that: 1) PKH67 fluorescence intensity decreases proportionately to number of cell divisions, 2) labeling with PKH67 does not alter either cell cycle distribution, as assessed by vital DNA staining with Hoechst 33342, or cell growth, and 3) using a simple threshold analysis method suitable for real-time sorting decisions, subpopulations of proliferating cells present at initial levels of ≥ 10% can readily be detected after two cell division times, based on decreased PKH67 intensity. Finally, we demonstrated that after treatment of an admixture of K562S and K562R with vincristine, triple-labeling with PKH67, annexin V, and propidium iodide can be used to identify and sort those cells which remain not only viable (nonnecrotic, nonapoptotic) but actively dividing (decreased PKH67 intensity) in the presence of drug. Conclusions: Although the studies described here were carried out in a model system using cells having known drug resistance phenotypes, we expect that the methods described will be useful in ex vivo studies of clinical leukemic specimens designed to identify the role played by specific chemoresistance proteins and mechanisms in therapeutic outcomes for individual patients.Cytometry (Comm. Clin. Cytometry) 42:50–60, 2000 © 2000 Wiley-Liss, Inc.

Published
2000
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2. A 13C method of estimation of carbon allocation to roots in a young chestnut coppice

Author

E. Deleens, M. Mousseau, and L. Mordacq

Subjects
Ecophysiology, biology, Physiology, Growing season, chemistry.chemical_element, Plant Science, Photosynthesis, biology.organism_classification, Fagaceae, Coppicing, Horticulture, chemistry, Botany, Respiration, Shoot, Carbon, Mathematics
Abstract

A method is described in which 1 year-old chestnut coppice was fed in situ with air highly enriched in 13CO2 (23%). After 3 days, 13C concentration increases in shoots were measured by mass spectrometry. Respiratory losses between 13C feeding and harvest were estimated using two different methods: (i) a model involving the temperature response of respiration and (ii) direct measurement of 13C content of the CO2 respired by the shoots during the night. Carbon allocation to roots was deduced by subtracting from the given amount of 13C, the amount remaining in shoots and the 13C respired by the shoots. The method was tested twice during the growing season. Very little carbon was allocated to roots in late July, but over 80% of assimilated 13C went to roots at the end of September. Despite some approximations in the 13C respiratory losses estimations, the method allowed evaluation of carbon allocation to roots with an error of about 5%.

Published
1986
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3. Carbon dioxide enrichment reduces shoot growth in sweet chestnut seedlings (Castanea sativa Mill.)*

Author

M. Mousseau and H. Z. Enoch

Subjects
Chlorophyll content, biology, Physiology, food and beverages, Growing season, Biomass, Plant Science, biology.organism_classification, Fagaceae, Horticulture, chemistry.chemical_compound, Nutrient, Dry weight, chemistry, Botany, Shoot, Carbon dioxide
Abstract

Two-year-old potted sweet chestnut seedlings were grown at 350 ppm CO2 and 700 ppm, day and night in constantly ventilated tunnels during two full growing seasons, near Paris, France (48° N, 2° E). Enrichment with CO2 caused an unusual shoot growth response. After the end of July, stem elongation ceased in 62% of the CO2 enriched plants as compared with 37% in the control. The leaves of CO2-enriched seedlings showed early senescence, indicated by premature yellowing and a decrease in chlorophyll content. This was associated with nutrient dilution brought about by the rapid growth of these trees. The increase in total dry weight of the CO2-enriched seedlings was essentially the result of increase in the root dry weight (69%). Shoot weight decreased by 22% relative to the control. Total leaf area per enriched plant was 25% smaller than the control. This unusual pattern of growth and carbon allocation of the CO2 treated Chestnut trees emphasizes the concept of a response specificity within trees to an increase of atmospheric CO2.

Published
1989
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4. Impact of creative art therapy on fatigue and quality of life in patients treated for localized breast cancer: A randomized study.

Author

Joly F, Pasquier D, Levy C, Mousseau M, D'Almeida MC, Noal S, Le Tinier F, Geffrelot J, Ciais C, Szymczak V, Leon C, Rousselot MP, Darbas S, Hanzen C, and Heutte N

Subjects
Anxiety therapy, Depression therapy, Female, Humans, Quality of Life, Art Therapy, Breast Neoplasms complications, Breast Neoplasms radiotherapy
Abstract

Background: Art therapy (AT) as supportive care may help patients cope with cancer treatments. This non-blinded randomized trial assessed the impact of creative AT on severe fatigue and quality of life (QoL) in localized breast cancer patients undergoing irradiation., Material and Methods: 320 patients were randomized to an AT group (ATG; 8 weekly sessions starting during irradiation) or to a standard group (SG). The primary endpoint was severe global fatigue (Functional Assessment of Chronic Therapy Fatigue subscale score <37) at 1 month post-irradiation. Quality of life (Fact-B), anxiety/depression (Hospital Anxiety and Depression Scale (HADS)) and different dimensions of fatigue 20-item Multidimensional Fatigue Inventory (MFI-20) were assessed at 1, 6 and 12 months post-irradiation. The secondary endpoints, fatigue among patients treated with chemotherapy, QoL (Fact-B), anxiety/depression (HADS) and different dimensions of fatigue (MFI-20) at 1, 6 and 12 months post-irradiation (with post hoc analysis in patients with treated with chemotherapy) were also assessed., Results: 82% of patients completed ≥8 sessions. Severe initial global fatigue was observed in 43% of patients in each group, and among in 64% of patients whose treatment protocol contained chemotherapy. At 1 month post-irradiation, 45% in the ATG and 57% of patients in the SG reported severe global fatigue (p = 0.37); among patients with initial severe mental fatigue (MFF), 79% and 44% had improved MFF (p = 0.007) respectively; similarly 79% and 44% with initial poor motivation had better mental motivation (p = 0.03). At 6 and 12 months, social well-being scores in the ATG were higher (21.3 and 21.4 vs. 19.8 and 19.2, p = 0.05 and p < 0.01) with a significant improvement for patients who had chemotherapy (41% vs. 18%, p = 0.017). A positive association was observed between the number of AT sessions, fatigue and QoL (p < 0.01)., Conclusion: AT did not significantly improve global severe fatigue among all cancer participants 1 month after radiation therapy, however it had a positive impact on social well-being and may improve MFF and motivation., (© 2022 John Wiley & Sons Ltd.)

Published
2022
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5. Impact of multidisciplinary tumour board in the management of ovarian carcinoma in the first-line setting. Exhaustive analysis from the Rhone-Alpes region.

Author

Ferraioli D, Bally O, Meeus P, Benayoun D, Bakrin N, De Saint Hilaire P, Beal Ardisson D, Provençal J, Barletta H, Mousseau M, Chauleur C, Verbaere S, Knibiehly A, Fuso L, Charreton A, Devouassoux-Shisheboran M, Chopin N, Glehen O, Labrosse-Canat H, Farsi F, and Ray-Coquard I

Subjects
Carcinoma, Ovarian Epithelial therapy, Chemotherapy, Adjuvant, Cytoreduction Surgical Procedures, Female, Humans, Neoadjuvant Therapy, Neoplasm Staging, Retrospective Studies, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Ovarian Neoplasms pathology
Abstract

Objective: Epithelial ovarian cancer (EOC) is a poor prognosis disease partly linked to diagnosis at an advanced stage. The quality of care management is a factor that needs to be explored, more specifically optimal organisation of first-line treatment., Methods: A retrospective study, dealing with all patients diagnosed within the Rhone-Alpes region with initial diagnosis EOC in 2012, was performed. The aim was to describe the impact of multidisciplinary tumour boards (MTB) in the organisation of care and the consequence on the patient's outcomes., Results: 271 EOC were analysed. 206 patients had an advanced EOC. Median progression-free survival (PFS) is 17.8 months (CI95%, 14.6-21.2) for AOC. 157 patients (57.9%) had a front-line surgery versus 114 patients (42.1%) interval debulking surgery. PFS for AOC patients with no residual disease is 24.3 months compared with 15.3 months for patients with residual disease (p = .01). No macroscopic residual disease is more frequent in the patients discussed before surgery in MTB compared with patients not submitted before surgery (73% vs. 56.2%, p < .001)., Conclusion: These results highlight the heterogeneity of medical practices in terms of front-line surgery versus interval surgery, in the administration of neoadjuvant chemotherapy and in the setting of MTB discussion., (© 2020 John Wiley & Sons Ltd.)

Published
2020
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7. Could ovarian choriocarcinoma be detected by maternal serum screening for Down syndrome?

Author

Gauchez AS, Dreux S, Stéfani L, Mousseau M, Jouk PS, and Muller F

Subjects
Adult, Choriocarcinoma blood, Down Syndrome diagnosis, Female, Humans, Infant, Newborn, Infant, Premature, Mass Screening, Ovarian Neoplasms blood, Pregnancy, Biomarkers, Tumor blood, Choriocarcinoma diagnosis, Chorionic Gonadotropin, beta Subunit, Human blood, Down Syndrome blood, Ovarian Neoplasms diagnosis
Abstract

The incidence of ovarian malignancies during gestation ranges from 1 in 8000 to 1 in 20,000 deliveries. Ovarian malignancies that produce human chorionic gonadotropin (hCG) are limited to germ cell tumors, of which dysgerminoma is the most frequent (45%) malignant type encountered in pregnant patients, the others being ovarian choriocarcinoma and mixed germ cell tumors (Boulay and Podczaski, 1998). In women of childbearing age, it is hard to distinguish between metastatic choriocarcinoma on a complete mole and primary ovarian choriocarcinoma. Treatment is based on adnexectomy followed by chemotherapy. Given the extreme rarity of these tumors, the long-term prognosis is difficult to establish. Had the diagnosis for our patient been made during pregnancy, the therapeutic approach would have been discussed in terms of gestational age. In the last trimester, we could have suggested cesarean section followed by adnexectomy, and then chemotherapy. In the second-trimester, chemotherapy could have been discussed, although the fetal toxicity of cisplatin chemotherapy is not firmly defined (Ferrandina et al., 2005). This treatment is an alternative to termination of pregnancy. We retrospectively studied maternal serum biochemistry so as to assess the possibility of a diagnosis of ovarian choriocarcinoma at the time of maternal serum screening for Down syndrome.

Published
2007
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8. Long term follow-up of ventilated patients with thoracic restrictive or neuromuscular disease.

Author

Brooks D, De Rosie J, Mousseau M, Avendaño M, and Goldstein RS

Subjects
Analysis of Variance, Carbon Dioxide blood, Exercise Test, Female, Humans, Male, Middle Aged, Neuromuscular Diseases blood, Oxygen blood, Pulmonary Ventilation, Thoracic Diseases blood, Ventilators, Mechanical, Lung physiopathology, Neuromuscular Diseases physiopathology, Thoracic Diseases physiopathology
Abstract

Objective: To evaluate the long term effects of home mechanical ventilation (HMV) on pulmonary function, nighttime gas exchange, daytime arterial blood gases, sleep architecture and functional exercise capacity (6 min walk). Patients with respiratory failure attributable to thoracic restrictive disease (TRD) (kyphoscoliosis) or neuromuscular disease (NMD) were assessed, ventilated, trained and followed in a dedicated unit for the care of patients requiring long term ventilation., Design: All patients admitted for home ventilation training since 1988 were reviewed. Measurements of lung function, gas exchange during wakefulness and sleep, as well as functional exercise capacity, were recorded before and immediately after the establishment of HMV. Measurements were repeated one to two years, five years and eight to 10 years later., Patients: Seventy-four individuals with TRD or NMD who completed the home ventilation training program and continued with HMV during all or part of the day for at least one year were studied., Results: Forty patients had TRD. The characteristics of these patients were (mean SE) as follows: age 58 2.4 years; vital capacity (VC) 27% 1.6% predicted, forced expiratory volume in 1 s (FEV1) 25% 1.5% predicted; FEV1/forced VC (FVC) 78% 1.8%. Thirty-four patients had NMD. The characteristics of these patients were as follows: age 44 3.1 years; VC 41% 4.9% predicted, FEV1 44 5.3% predicted; FEV1/FVC 83% 4.2%. There was a significant improvement in distance walked in 6 min (maximum change 51.2 m in patients with NMD and 93.0 m in patients with TRD), daytime partial pressure of arterial carbon dioxide (maximum change 12.9 mmHg in patients with NMD and 10.4 mmHg in patients with TRD) and nighttime partial pressure of arterial carbon dioxide (maximum change 11.7 mmHg in patients with NMD and 18.0 mmHg in patients with TRD) over time (P 0.004). Ventilation resulted in an improvement in partial pressure of arterial oxygen in patients with TRD (68.1 2.8 mmHg to 80.1 3.5 mmHg) and in patients with NMD (52.9 1.7 mmHg to 65.3 2.1 mmHg), although the change was not statistically significant in patients with NMD (P=0.001 in patients with TRD; P=0.105 in patients with NMD). The improvement after ventilation was maintained over several years. Sleep efficiency (75% 18%, 79% 2.2%), the arousal index (13.4 13 events/h, 28.2 17 events/h) and the apnea-hypopnea index (10.1 11.3 events/h, 13.9 9.5 events/h) did not change with time in either patients with TRD or patients with NMD, respectively (P 0.5)., Conclusions: HMV was associated with sustained, long term improvements in nighttime and daytime gas exchange in patients with TRD and NMD. Function exercise capacity increased in patients with TRD and in a subgroup of ambulatory patients with NMD. In patients with TRD, these improvements were maintained for up to 10 years after HMV was established.

Published
2002
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