Gliomas are the most common primary brain tumors. To date, therapies do not allow curing patients... more Gliomas are the most common primary brain tumors. To date, therapies do not allow curing patients, and glioblastomas (GBMs) are associated with remarkably poor prognosis. This situation is at least partly due to intrinsic or acquired resistance to treatment, especially to chemotherapy. In 2005, temozolomide (TMZ) has become the first chemotherapeutic drug validated for GBM. Nevertheless TMZ efficacy depends on Mgmt status. While the methylation of Mgmt promoter was considered so far as a prognostic marker, its targeting is becoming an effective therapeutic opportunity. Thus, arrival of both TMZ and Mgmt illustrated that considerable progress can still be realized by optimizing adjuvant chemotherapy. A part of this progress could be accomplished in the future by overcoming residual resistance. The aim of the present study was to investigate the involvement of a set of other DNA-repair genes in glioma resistance to temozolomide. We focused on DNA-repair genes located in the commonly d...
Acoustic cavitation is a way to improve local drug delivery in tumors. When no external nucleatio... more Acoustic cavitation is a way to improve local drug delivery in tumors. When no external nucleation agents are injected, high negative pressures are required for initiating inertial cavitation, which can lead to biological damages. In the present study, unseeded inertial cavitation was obtained in vivo using confocal beams and the effect of these exposure conditions was assessed on drug structure and activity, shallow tissues and growth of breast tumors. No change was observed on structure and cytotoxicity of doxorubicin after sonication. Experiments were conducted on healthy rats, exposing the thigh and abdomen. Histological analyses at 72 hours and 2 weeks post-treatment demonstrated only a modest impact on tissues, mainly resulting in mild skin damages. Finally, 4T1 breast tumors in mice were sonicated. Immunohistochemical analyses showed that the exposures of mammary tumors did not impact vascular density, proliferation, nor the proliferation and apoptosis of cancer cells. Moreover, ultrasound did not negatively impact on the spreading of cancer cells to the lungs and bone marrow. Thus, our study provides experimental evidence that these particular ultrasound parameters can be used safely for unseeded inertial cavitation in vivo.
Gliomas are the most common primary brain tumors. To date, therapies do not allow curing patients... more Gliomas are the most common primary brain tumors. To date, therapies do not allow curing patients, and glioblastomas (GBMs) are associated with remarkably poor prognosis. This situation is at least partly due to intrinsic or acquired resistance to treatment, especially to chemotherapy. In 2005, temozolomide (TMZ) has become the first chemotherapeutic drug validated for GBM. Nevertheless TMZ efficacy depends on Mgmt status. While the methylation of Mgmt promoter was considered so far as a prognostic marker, its targeting is becoming an effective therapeutic opportunity. Thus, arrival of both TMZ and Mgmt illustrated that considerable progress can still be realized by optimizing adjuvant chemotherapy. A part of this progress could be accomplished in the future by overcoming residual resistance. The aim of the present study was to investigate the involvement of a set of other DNA-repair genes in glioma resistance to temozolomide. We focused on DNA-repair genes located in the commonly d...
Acoustic cavitation is a way to improve local drug delivery in tumors. When no external nucleatio... more Acoustic cavitation is a way to improve local drug delivery in tumors. When no external nucleation agents are injected, high negative pressures are required for initiating inertial cavitation, which can lead to biological damages. In the present study, unseeded inertial cavitation was obtained in vivo using confocal beams and the effect of these exposure conditions was assessed on drug structure and activity, shallow tissues and growth of breast tumors. No change was observed on structure and cytotoxicity of doxorubicin after sonication. Experiments were conducted on healthy rats, exposing the thigh and abdomen. Histological analyses at 72 hours and 2 weeks post-treatment demonstrated only a modest impact on tissues, mainly resulting in mild skin damages. Finally, 4T1 breast tumors in mice were sonicated. Immunohistochemical analyses showed that the exposures of mammary tumors did not impact vascular density, proliferation, nor the proliferation and apoptosis of cancer cells. Moreover, ultrasound did not negatively impact on the spreading of cancer cells to the lungs and bone marrow. Thus, our study provides experimental evidence that these particular ultrasound parameters can be used safely for unseeded inertial cavitation in vivo.
Uploads
Papers by Sandra Geraci