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C Bailly

Publications and source records attributed to C Bailly.

324 records · Page 18Linked to original sources

Early CYFRA 21-1 variation predicts tumor response to chemotherapy and survival in locally advanced non-small cell lung cancer patients.

We have evaluated CYFRA 21-1 serum level variations as an indicator of tumor response and survival in 44 consecutive patients with locally advanced non-small cell lung cancer (NSCLC) treated with induction chemotherapy (IC). Irrespective of the initial CYFRA 21-1 serum concentration, a more than 65% decrease in the serum level after the first chemotherapy course was significantly predictive of an objective tumor response (p = 0.0022). In addition, a more than 80% decrease in this level significantly predicted a better disease-free survival (p = 0.039). In patients with initial CYFRA 21-1 serum levels > 3.3 ng/mL (n = 29), a more than 80% decrease after the first IC course was the most significant predictor of overall survival (p = 0.025) in a Cox analysis including initial staging, tumor response and surgery. We conclude that early monitoring of CYFRA 21-1 serum levels may be a useful prognostic tool for tumor response and survival in stage III NSCLC patients treated by induction chemotherapy.

Adult↗

A pilot survey of social work services in pediatric primary care programs in urban teaching hospitals.

OBJECTIVE: To determine the current status of social work presence in pediatric primary care clinics in urban teaching hospitals. DESIGN: Survey instrument mailed to the medical directors of outpatient pediatrics in the major pediatric teaching hospital of approved residency programs in the 100 largest metropolitan areas in the United States. RESULTS: Sixty responses (60%) were received. Eighty percent of practices reported having on-site social work services, with a median of 14,805 annual clinic visits per social work full-time equivalent. Ninety-five percent of respondents considered on-site social work services in pediatric primary care to be important, whereas half of respondents considered social work services "less than adequate" at their site, and most of these felt this inadequacy had led to additional hospital visits or other adverse outcomes. There were no significant associations of reported adequacy of social work services with any characteristics of hospital, practice, or population. CONCLUSION: Pediatric primary care clinicians at teaching hospitals consider on-site social work services to be important, but most report these services are less than adequate in their practices, and for many, adequacy has declined.

Child↗

Initial management of advanced Burkitt lymphoma in children: is there still a place for surgery?

This retrospective study compared the overall survival, the event-free survival, and the timing of chemotherapy in patients with advanced Burkitt lymphoma with and without laparotomy. Thirty-five patients with advanced abdominal Burkitt lymphoma treated at least partially at the Centre Léon Bérard between 1981 and 1992 were included in this study. The diagnosis was obtained by laparotomy (LAP group) in 21 patients (17 stage III, 4 stage IV) and by other methods (non-LAP group) in 14 patients (5 stage III, 9 stage IV). The overall survival (71 and 93%) and the event-free survival (66 and 79%) were similar in the LAP and non-LAP groups, and the relapse rate was five (three local) in the LAP group compared with three (none local) in the non-LAP group. The local complication rate (9 of 21 versus 2 of 14) and the toxic death rate (2 of 21 versus 1 of 14) were slightly higher in the LAP group. Laparotomy also caused delays in therapy and increased the overall hospital stay. The mean interval from diagnosis to the start of the fourth course of chemotherapy was 57 days compared with 48 days and the average hospital stay was 44.4 days compared with 39 days for the LAP and non-LAP groups, respectively. Because advanced Burkitt lymphoma can be diagnosed by fine-needle aspiration, and chemotherapy cures more than 80% of the patients, there is no need for initial surgery, apart from acute emergencies. Furthermore, laparotomy delay chemotherapy and might reduce the survival rate.

Adolescent↗

[PKC 412].

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Antineoplastic Agents↗

The plant alkaloid usambarensine intercalates into DNA and induces apoptosis in human HL60 leukemia cells.

Usambarensine is a plant alkaloid isolated from the roots of Strychnos usambarensis collected in Central Africa. This bis-indole compound displays potent antiamoebic activities and shows antigardial, antimalarial and cytotoxic effects. Usambarensine is highly toxic to B16 melanoma cells and inhibits the growth of leukemia and carcinoma cells. To date, the molecular basis for its diverse biological effects remains totally unknown. However, its capacity to inhibit nucleic acids synthesis in melanoma cells, on the one hand, and its structural analogy with DNA-binding pyridoindole plant alkaloids recently studied (cryptolepine and matadine), on the other hand, suggested that usambarensine could also bind to DNA. Consequently, we studied the strength and mode of binding to DNA of usambarensine by means of absorption, circular and linear dichroism. The results of the optical measurements indicate that the alkaloid effectively binds to DNA and behaves as a typical intercalating agent. Biochemical experiments indicated that, in contrast to cryptolepine and matadine, usambarensine does not interfere with the catalytic activity of topoisomerase II. Human HL60 leukemia cells were used to assess the cytotoxicity of the alkaloid and its effect on the cell cycle. Usambarensine treatment is associated with a loss of cells in the G1 phase accompanied with a large increase in the sub-G1 region which is characteristic of apoptotic cells. The DNA of usambarensine-treated cells was severely fragmented and the proteolytic activity of DEVD-caspases is enhanced. Usambarensine is thus characterized as DNA intercalator inducing apoptosis in leukemia cells.

Alkaloids↗

DNA but not topoisomerases is a target for a cytotoxic benzo[5,6]cyclohepta[b]indol-6-one derivative.

The interaction of a newly designed benzocycloheptaindol-6-one derivative with DNA has been investigated by complementary spectroscopic techniques including absorption, circular and linear dichroism. Footprinting measurements were performed to delineate the sequence-selectivity of the drug-DNA interaction and a plasmid relaxation assay was used to study the effects of the drug on human DNA topoisomerases I and II. The results clearly indicated that the test compound behaves as a typical DNA intercalating agent but does not stimulate DNA cleavage by topoisomerases. At the cellular level, the cytometry measurements showed that the drug provoked a marked accumulation of HL60 human leukemia cells in the G2/M phase of the cell cycle. DNA is thus identified as a valid target for this new series of drugs particularly toxic to human (HL60) and murine (P388) leukemia cells.

Animals↗

Topoisomerase I-DNA covalent complexes in human colorectal cancer xenografts with different p53 and microsatellite instability status: relation with their sensitivity to CTP-11.

The topoisomerase I poison CPT-11 has proved efficient for the treatment of untreated metastatic colorectal cancers (CRC) and those refractory to fluoropyrimidines. However, the interpatient variability is important. A previous in vitro study suggested that measurements of the level of topoisomerase I-DNA intermediates trapped by camptothecin may be useful to estimate the chemosensitivity of colon carcinoma cell lines. To verify this hypothesis, we developed an immuno-assay to detect covalent topoisomerase I-DNA complexes in a series of human colorectal cancers xenografted in nude mice. Six human CRCs were selected for their distinctive p53 and microsatellite instability (MSI) status. Tumour lysates, prepared from mice untreated or treated with CPT-11, were fractionated onto CsCl gradients to separate free and DNA-bound topoisomerase I by centrifugation. Interestingly, significant levels of DNA-topoisomerase I complexes were detected in the tumours most responsive to the treatment with CPT-11, irrespective of their MSI and p53 phenotypes. Our in vivo study fully agrees with the predictions from the in vitro data indicating that evaluation of topoisomerase I-DNA complexes would be useful to predict the response of CRC to a treatment with CPT-11.

Animals↗

Synthesis and biological activities of indolocarbazoles bearing amino acid residues.

Three indolocarbazole compounds bearing a tripeptide or a lysine group attached to one of the indole nitrogens via a propylamino chain and two rebeccamycin derivatives bearing a lysine residue on the sugar moiety were synthesised with the aim of improving the binding to DNA and the antiproliferative activities. Four tumour cell lines, from murine L1210 leukemia, human HT29 colon carcinoma, A549 non-small cell lung carcinoma and K-562 leukemia, were used to evaluate the cytotoxicity of the drugs. Their effects on the cell cycle of L1210 cells and their antimicrobial properties against two Gram-positive bacteria Bacillus cereus and Streptomyces chartreusis, a Gram-negative bacterium Escherichia coli and a yeast Candida albicans were also investigated.

Amino Acids↗

DNA binding properties of the indolocarbazole antitumor drug NB-506.

Indolocarbazoles derived from the antibiotic rebeccamycin represent an important group of antitumor agents. Several indolocarbazoles are currently undergoing clinical trials. These compounds inhibit topoisomerase 1 to produce DNA breaks that are responsible for cell death. Unlike classical topoisomerase I poisons like camptothecin, glycosyl indolocarbazoles can form stable complexes with DNA even in the absence of topoisomerase I. At least in part, their mode of action is reminiscent of that of the anthracyclines, which also bind to nucleic acids and interfere with topoisomerase II. The lead synthetic compound in the series is the uncharged drug NB-506, which bears a glucose residue attached to the indolocarbazole chromophore substituted with two hydroxyl groups at positions 1 and 11. Here we report a detailed biophysical study aimed at characterizing the DNA binding properties of NB-506. Molecular modeling was used to compare the conformation and electronic properties of NB-506 and its analogue ED-571 bearing the two hydroxyl groups at positions 2 and 10. Surface plasmon resonance experiments, performed with DNA hairpin oligomers, indicate that NB-506 binds almost equally well to both AT and GC base pairs, and the binding affinity (K = 10(5) M(-1)) is similar to that of certain classical intercalators such as amsacrine and bisantrene. Isothermal titration calorimetry experiments show that the binding of NB-506 is enthalpy-driven (deltaH = -7.2 kcal/mol). The binding enthalpy measured for NB-506 is similar to that obtained with doxorubicin but the DNA interaction processes for the two drugs differ markedly in terms of entropy and deltaG. The free energy of NB-506 binding to DNA is considerably less favorable than that of doxorubicin. These biophysical data help us to understand further how rebeccamycin-type anticancer drugs interact with DNA.

Algorithms↗

Can MIBG scan replace the need for bone marrow assessment at diagnosis and reassessment in stage 4 neuroblastomas?

UNLABELLED: Complete staging (extensive marrow investigation and meta-iodo benzylguanine (MIBG) scan) is considered as mandatory both at diagnosis and after chemotherapy for assessment of metastases in neuroblastomas. However the correlation between bone marrow invasion and uptake of MIBG at metastatic sites remains unclear. This study investigates whether MIBG alone is sufficiently sensitive to make these procedures redundant. PATIENTS AND METHODS: 20 children over one year of age, with histologically proven metastatic neuroblastoma were studied. Extensive bone marrow assessment and MIBG bone scan performed both at diagnosis and after completion of induction chemotherapy were reviewed. RESULTS: At diagnosis metastases were detected by marrow investigation alone in 2, MIBG alone in 2 and both procedures in 16. After induction chemotherapy metastases were detected by only marrow investigation in 2, by only MIBG in 3, by both procedures in 6 patients, and by none in 9. CONCLUSIONS: Whether marrow investigations and MIBG scan explore the same phenomenon remains unclear. However it appears that marrow disease that is histologically detectable may remain MIBG negative both at diagnosis and after treatment. Both procedures are still justified at time of diagnosis and evaluation of response.

3-Iodobenzylguanidine↗

[Comparative study of the tumor regression rate of 127 uveal melanomas irradiated with 106 Ru/106 Rh. Attempted analysis of the correlations between per-operative cytology and histopathology of the enucleated eye and the tumoral regression on the one hand, and general prognosis on the other hand].

A study of the speed of tumor regression in 127 uveal melanomas treated with beta-rays brachyterapy, since June 1983, allows a division into 2 groups: radiosensitive forms with a volume less than 50% in the following year, and radioresistant forms. Correlation between radio sensitivity and tumor cell type were obtained with intraoperative cytopunction, and showed the prevalence of epithelioid type. The results of enucleation indicate the prevalence of fusiform type inside the radioresistant tumor group. No precise correlation could be brought between death and the previous data, the most important negative criteria being the level of initial tumor height equal or superior to 7 mm.

Adult↗

Effects of an androgenic derivative on the development of chemically-induced mammary carcinogenesis in the rat.

The effects of an androgenic derivative--danazol--on the development of dimethylbenz(a)anthracene (DMBA)-rat mammary carcinogenesis were studied. Animals in the treated group received danazol (10-12 mg/kg/day) during 169 days, starting 5 days after DMBA induction. As compared with tumours in control animals, those treated with danazol appear later and are significantly smaller. Moreover, this treatment reduced the incidence of animals affected by mammary cancer and the average number of malignant tumours in each animal. In the same way, the incidence of animals with missing nodules was significantly higher in the group treated with danazol. It is concluded that danazol has an inhibitory effect on experimental mammary tumours. This effect seems to be greater the earlier the treatment is started and the longer time it is applied.

9,10-Dimethyl-1,2-benzanthracene↗

[Control of an epidemic of meningococcal meningitis in Central Africa].

A severe epidemic of group A meningococcal disease occurred in the northwest part of the Central African Republic from January to March 1992. The outbreak affected a large and densely populated area, with a poor road network, located 400 kilometers south of the classical meningitis belt. An initial selective vaccination campaign was carried out by the national health care service. As the epidemic was continuing, the national authorities asked for international assistance. The French participated by sending Bioforce, a medical task force designed by the Ministry of Defense, with the financial support of the Ministry of Cooperation. Neisseria meningitidis strains were isolated and identified within 36 hours by the Bioforce field laboratory. Strains from 24 patients were sent to the Pasteur Institute in Paris (Neisseria Unit) for serotyping, testing of antibiotic susceptibility, and multilocus enzyme electrophoresis. With one exception, all strains had formula A:4:P1.9. By an initial rapid assessment, the limits of the affected area and populations were determined. The weekly incidence rates observed in different areas varied within a range of 3 to 10 cases per 1,000, with fatality rates from 20 to 30 cases per 100. The spread of the epidemic was stopped by a mass vaccination campaign, which targeted the entire population (200,000 immunizations) of the affected area. The case fatality rate could not be reduced below 15%, despite antimicrobial treatments implemented as soon as possible. The optimal treatment was the standard single intramuscular injection of oily chloramphenicol. The predictive values of clinical symptoms were calculated. The efficacy of vaccination was estimated by comparison of the percentage of people immunized and the proportion of those vaccinated people who developed meningitis identified during the 3 weeks following the mass vaccination campaign. The efficacy varied between 93 to 95% according to the place. The typical weekly incidence rate of 1 case per 1,000 is not a relevant threshold to sufficiently and immediately detect a meningitis outbreak and needs to be reconsidered.

Adolescent↗