Biomedical subjects

E Deniaud-Alexandre

Publications and source records attributed to E Deniaud-Alexandre.

23 records · Page 2Linked to original sources

PubMed2000

Poly(ADP-ribose) polymerase, a major determinant of early cell response to ionizing radiation.

PURPOSE: To determine whether DNA-dependent protein kinase (DNA-PK) and poly(ADP-ribose) polymerase (PARP-1) are involved in eliciting the rapid fluctuations of radiosensitivity that have been observed when cells are exposed to short pulses of ionizing radiation. MATERIALS AND METHODS: The effect of DNA-PK and PARP-1 inhibitors on the survival of cells to split-dose irradiation was investigated using Chinese hamster V79 fibroblasts and human carcinoma SQ-20B cells. The responses of PARP-1 proficient and PARP-1 knockout mouse 3T3 fibroblasts were compared in a similar split-dose assay. RESULTS: Inactivation of DNA-PK by wortmannin potentiated radiation-induced cell kill but it did not alter the oscillatory, W-shaped pattern of early radiation response. In contrast, oscillatory radiation response was abolished by 3-aminobenzamide, a reversible inhibitor of enzymes containing a PARP catalytic domain. The oscillatory response was also lacking in PARP-1 knockout mouse 3T3 fibroblasts. CONCLUSION: The results show that PARP-1 plays a key role in the earliest steps of cell response to ionizing radiation with clonogenic ability or growth as endpoint. It is hypothesized that rapid poly(ADP-ribosylation) of target proteins, or recruitment of repair proteins by activated PARP-1 at the sites of DNA damage, bring about rapid chromatin remodelling that may affect the incidence of chromosomal damage upon re-irradiation.

3T3 Cells↗

PubMed2000

[New administration modalities for radiotherapy in lung cancer].

Much progress has been made in recent years in administration modalities for radiotherapy for lung cancer. Exposure time to external irradiation was the first parameter to be modified: hyperfractionated radiotherapy, hyperfractionated accelerated radiotherapy with or without concomitant irradiation, synchronous or asynchronous protocols, split course radiotherapy. Radiosensitizing agents have also been the subject of much research: radiosensitization of hypoxic cells, modifiers of the biological response, concomitant radiochemotherapy. The main drugs used are 5-fluorouracil, platinum salts, etoposide, hydroxyurea, taxanes, topotecan, vinorelbin, and gemcitabine. Outcome with these combinations is discussed, both for non-small-cell and small-cell lung cancer. 3D conformational radiotherapy can enable increased dosing in the tumoral target while better preserving healthy tissues. High dose endoluminal brachytherapy is used particularly as a palliative treatment for bronchial obstructions or as curative treatment for weakly infiltrative small endoluminal tumors.

Antineoplastic Agents↗

PubMed2000

[Postoperative radiotherapy after complete resection of stage II (N1) non-small-cell lung cancer: reasons for not proposing it].

Postoperative external radiation in non-small-cell lung cancer has remained a topic of debate since the first randomized study examining the potential contribution of postoperative radiotherapy published more than 35 years ago and despite a recent meta-analysis published in 1998 that included 9 randomized prospective studies. Among the 4 eligible randomized studies including non-small-cell lung cancer patients in complete remission of stage II (N1) disease, none demonstrated a significant advantage on survival. In addition, some of these studies disclosed an apparently deleterious effect after postoperative radiotherpy. Although the modalities and the technical quality of radiotherapy and surgical resection were different for the different studies or within a given study, or in some of the older studies even obsolete, and although the precision of the outcome evaluation can be criticized, there is currently no argument for proposing postoperative radiotherapy as a routine systematic practice with conventional methods of bidimensional dosimetric planification after complete surgical resection with good quality mediastinal node dissection for non-small-cell lung cancer patients with stage II (N1) disease. However, the contribution of postoperative radiotherpy with sufficient means for performing tridimensional conformational radiotherapy with individual optimization of computerized dosimetric planification taking into account the residual respiratory function after surgery remains to be evaluated in randomized prospective studies with rigorous control of the technical quality of the surgical resection and the radiotherapy and a precise statistical analysis of the locoregional and distant events in case of incomplete surgical resection and in more advanced stage disease (parietal T3, N0, stage III N2).

Carcinoma, Non-Small-Cell Lung↗

PubMed1998

[Localized or metastatic cancer of the prostate: review of new treatment modalities].

Amongst men, prostatic adenocarcinoma is the most common cancer and the second most frequent cause of deaths. Widespread PSA measurement have led to earlier diagnosis. Recent clinical trials have tried to show an improvement in the prognosis. Early stages are mainly treated surgically even if local control results are similar with radiotherapy. Radiotherapy is the main stay of treatment for more locally advanced disease, either conventionally or conformational. Adjuvant hormonotherapy has been shown to improve survived as opposed to neoadjuvant hormonotherapy which only has local effects. The treatment of metastatic disease is palliative with the use of antiandrogens. In case of relapse, a second line of hormonotherapy or a chemotherapy is given. However the problem is the lack of effective drugs. Response rates to the main drug treatment are around 10 to 20%. New therapeutic approaches are now based on antimicrotubules agents but it is difficult to evaluate their efficacity. Further clinical trials will provide more information about improvement in survival rates and in quality of life.

Humans↗

PubMed1997

[Early cell response to radiation].

The early steps of cellular radiation response have been investigated using a linear electron accelerator operated in a split-dose mode, in such a way that the time intervals between pulse exposures to relativistic electrons ranged from fractions of a second to a few minutes. The initial dose brought about large, synchronous changes in radiation sensitivity and generated a tetraphasic, W-shaped time-dependent profile of cell survival upon the second radiation exposure. While this time-related process was observed in most cell lines investigated, its kinetic parameters varied significantly from one cell line to the other. The number of DNA strand breaks (neutral and alkaline DNA filter elution) and the level of apoptosis (gel electrophoresis and flow cytometry) induced at the different phases of the time-dependent profile showed no relationship with the W-effect. It is presently hypothesized that mechanisms involved in molecular recognition of radio-induced lesions and initiation of genomic instability play a major role in this effect. Whatever the mechanism involved, the split-dose irradiation in the range of seconds enables dissecting the early steps of radiation response. The relevance of the W-effect to radiation therapy and technical drawbacks are discussed.

Cell Cycle↗