Biomedical subjects

Cynthia Ménard

Publications and source records attributed to Cynthia Ménard.

21 records · Page 2Linked to original sources

PubMed2003

Radiation abscopal antitumor effect is mediated through p53.

The observation that radiation treatment to a local area of the body results in an antitumor effect for tumors distant to the radiation site has been termed the "abscopal effect." To understand the mechanism of this unusual phenomenon, we examined whether the effect was mediated through p53, a protein complex up-regulated in irradiated cells. Non-tumor-bearing legs of C57BL/6 (wild-type p53) and p53 null B6.129S2-Trp53(tm1Tyj) mice were irradiated to determine whether an abscopal effect could be observed against Lewis lung carcinoma (LLC) and T241 (fibrosarcoma) implanted at a distant site. In mice with wild-type p53, both LLC and T241 tumors implanted into the midline dorsum grew at a significantly slower rate when the leg of the animal was exposed to five 10-Gy fractions of radiation compared with sham-irradiated animals, suggesting that the abscopal effect is not tumor specific. When the radiation dose to the leg was reduced (twelve fractions of 2 Gy each), the inhibition of LLC tumor growth was decreased indicating a radiation-dose dependency for the abscopal effect. In contrast, when the legs of p53 null animals or wild-type p53 mice treated with pifithrin-alpha (a p53 blocker) were irradiated (five 10-Gy fractions), tumor growth was not delayed. These data implicate p53 as a key mediator of the radiation-induced abscopal effect and suggest that pathways downstream of p53 are important in eliciting this response.

Animals↗

PubMed2003

Clinical trial of endorectal amifostine for radioprotection in patients with prostate cancer: rationale and early results.

Tolerance of the normal rectal mucosa to radiation injury limits the dose that can be safely delivered to the prostate gland with definitive external beam radiation therapy. The radioprotective agent amifostine (Ethyol; MedImmune, Inc, Gaithersburg, MD) is approved for intravenous use. Laboratory studies indicate that rectal administration results in preferential accumulation of amifostine in the rectal mucosa, and in clinical studies, neither free parent compound nor free active metabolite has been detected in the systemic circulation. This trial evaluates the rates of early and late rectal toxicities in patients with prostate cancer receiving definitive or adjuvant three-dimensional conformal external beam radiation therapy and concurrent daily endorectal applications of amifostine. Endpoints include Radiation Therapy Oncology Group acute and late toxicity gradings, Expanded Prostate Cancer Index Composite self-assessment questionnaires, and proctoscopic examinations with scoring of mucosal damage measured before, during, and after treatment. Eleven patients have been enrolled to date; 10 have completed radiotherapy and three have been followed-up to 6 months. Two patients received 66 Gy to the prostatic bed post-prostatectomy; five patients received 74 Gy and three received 76 Gy to the prostate gland. In all patients, daily fractionation was 2 Gy, and 1 g of amifostine (50 mg/mL in 20 mL reconstituted saline) was administered endorectally 40 minutes before radiation delivery. Daily endorectal administration was well tolerated. To date, six patients have experienced grade 2 (Radiation Therapy Oncology Group) acute toxicities, all but one because of frequent bowel movements relieved by loperamide. The initial trial will proceed until 18 patients are accrued, at which time an interval evaluation of both early and late toxicity endpoints will be conducted.

Adenocarcinoma↗

PubMedDate not supplied

An interventional magnetic resonance imaging technique for the molecular characterization of intraprostatic dynamic contrast enhancement.

The biological characterization of an individual patient's tumor by noninvasive imaging will have an important role in cancer care and clinical research if the molecular processes that underlie the image data are known. Spatial heterogeneity in the dynamics of magnetic resonance imaging contrast enhancement (DCE-MRI) is hypothesized to reflect variations in tumor angiogenesis. Here we demonstrate the feasibility of precisely colocalizing DCE-MRI data with the genomic and proteomic profiles of underlying biopsy tissue using a novel MRI-guided biopsy technique in a patients with prostate cancer.

Biopsy↗