Olivier Kerdraon

Using human CD20-transfected murine lymphomatous B cells to evaluate the efficacy of intravitreal and intracerebral rituximab injections in mice.

PURPOSE The treatment of primary central nervous system lymphoma (PCNSL) and its subset, primary intraocular lymphoma (PIOL), remains of limited efficiency, and salvage therapies are often used without prior testing in adequate animal models. Most PNCSL/PIOL are aggressive B-cell malignancies. Two animal models that closely mimic the human situation were established to evaluate the efficiency of intravitreal and intracerebral anti-CD20 monoclonal antibody (rituximab) injections. METHODS Human CD20-transfected murine B-lymphoma cells (38C13 CD20(+)) were inoculated in the vitreous through the pars plana or in the caudate nucleus with the use of a stereotaxic frame in immunocompetent syngeneic mice. Animals were monitored clinically and by funduscopic and histologic examination. Rituximab was injected intravitreally or intracerebrally. Occurrences of exophthalmia, neurologic disturbance, and weight loss were monitored over 2 months. RESULTS Inoculation of 38C13 CD20(+) cells in the eye or the brain resulted in tumor occurrence after a median of 15 days or 22 days, respectively, with histologic characteristics closely resembling those of PIOL and PCNSL. Local rituximab injections eradicated tumor colonization in more than half the graft recipients and inhibited tumor progression significantly in the others compared with progression in mice that underwent grafting with the control 38C13 cell line (no human CD20 expression) and in mice that underwent grafting with 38C13 CD20(+) cells that received local injections of an irrelevant antibody (trastuzumab). CONCLUSIONS Inoculation of native or human CD20-transfected murine 38C13 cells in the vitreous or the brain of immunocompetent mice provides useful novel models for evaluating the biology and treatment of PIOL and PCNSL. Intravitreal and intracerebral rituximab injections reduced tumor occurrence and growth in each model.

Tératomes ovariens matures et immatures: caractéristiques en échographie, TDM et IRM

Mature cystic ovarian teratomas, also called dermoid cysts, are one of the most frequent ovarian tumors of younger female patients and are suggested when a fat-containing cystic tumor is identified on imaging. However, the presence of fat is not pathognomonic for dermoid cyst, and it may also be identified in immature teratomas, whose prognosis and treatment are different. Some imaging features are helpful to differentiate between both tumors, including th epresence of enhancement on CT and MRI. Knowledge of the imaging features of these tumors allows for a confident diagnosis to be made in most cases. A few rare and less typical imaging features should also be recognized.

Assessment of the specificity of a new folate-targeted photosensitizer for peritoneal metastasis of epithelial ovarian cancer to enable intraperitoneal photodynamic therapy. A preclinical study

BACKGROUND Ovarian cancers prognosis remains dire after primary therapy. Recurrence rate is disappointingly high as 60% of women with epithelial ovarian cancer considered in remission will develop recurrent disease within 5 years. Special attention to undetected peritoneal metastasis during surgery is necessary as they are the main predictive factors of recurrences. Folate Receptor α (FRα) shows promising prospects in targeting ovarian cancerous cells and intraperitoneal photodynamic therapy (PDT) could be a solution in addition to macroscopic cytoreductive surgery to treat peritoneal micrometastasis. The aim of this preclinical study is to assess the specificity of a folate-targeted photosensitizer for ovarian peritoneal micrometastasis. METHODS We used the NuTu-19 epithelial ovarian cancer cell line to induce peritoneal carcinomatosis in female Fischer 344 rats. Three groups of 6 rats were studied (Control (no photosensitizer)/Non-conjugated photosensitizer (Porph)/Folate-conjugated photosensitizer (Porph-s-FA)). Four hours after the administration of the photosensitizer, animals were sacrificed and intraperitoneal organs tissues were sampled. FRα tissue expression was evaluated by immunohistochemistry. Tissue incorporation of photosensitizers was assessed by confocal microscopy and tissue quantification. RESULTS FRα is overexpressed in tumor, ovary, and liver whereas, peritoneum, colon, small intestine, and kidney do not express it. Cytoplasmic red endocytosis vesicles observed by confocal microscopy are well correlated to FRα tissue expression. Photosensitizer tissue quantification shows a mean tumor-to-normal tissue ratio of 9.6. CONCLUSION We demonstrated that this new generation folate-targeted photosensitizer is specific of epithelial ovarian peritoneal metastasis and may allow the development of efficient and safe intraperitoneal PDT procedure.

Shear Wave Elastography (SWE): An Analysis of Breast Lesion Characterization in 83 Breast Lesions

Qualitative and quantitative shear wave elastography (SWE) criteria were assessed to differentiate between malignant and benign breast lesions. This prospective study included 83 lesions. SWE features measured included maximal stiffness values inside the lesion (E(lesion)) and in the peri-lesion area (E(perilesion)) and ratio values (R(lesion) and R(perilesion)) according to the formula E(lesion) or E(perilesion)/E(fat), with E(fat) corresponding to normal fatty tissue. We compared ultrasonography (B-mode), SWE and histologic sizes. With qualitative and quantitative SWE analysis, sensitivity was 94% and specificity 73%. Malignant lesions appeared more heterogeneous, with higher stiffness and ratio values than benign lesions (p < 0.001). For malignant lesions, SWE size was better correlated to histologic size than B-mode size. Using benign SWE signs to selectively downgrade category 4a and 4b lesions, the specificity improved from 13% to 51% without loss in sensitivity (100%) compared to ultrasound.

Fischer 344 Rat: A Preclinical Model for Epithelial Ovarian Cancer Folate-Targeted Therapy.

Objective Ovarian cancer prognosis remains dire after primary therapy. Recurrence rates are disappointingly high as 60% of women with advanced epithelial ovarian cancer considered in remission will develop recurrent disease within 5 years. Special attention to undetected peritoneal metastasis and residual tumorous cells during surgery is necessary as they are the main predictive factors of recurrences. Folate receptor &agr; (FR&agr;) shows promising prospects in targeting ovarian cancerous cells. Our aim was to determine if the Fischer model described by Rose et al could be used to evaluate folate-targeted therapies in preclinical studies. Methods NuTu-19 epithelial ovarian cancer cell line was used to induce peritoneal carcinomatosis in female Fischer 344 rats. FR&agr; expression by NuTu-19 cells was assessed in vitro by immunofluorescence using “Cytospin®” protocol. In vitro folate-targeted compound uptake by NuTu-19 cells was evaluated by incubation of FR&agr;-positive ovarian cancer cell lines (NuTu-19/SKOV-3/OVCAR-3/IGROV-1) with or without (control) a folate-targeted photosensitizer. Intracellular incorporation was assessed by confocal microscopy. Determination of in vivo FR&agr; tissue expression by several organs of the peritoneal cavity was studied by immunohistochemistry. Results NuTu-19 cells express FR&agr; which allows intracellular incorporation of folate-targeted compound by endocytosis. FR&agr; is expressed in tumor tissue, ovary, and liver. Peritoneum, colon, small intestine, and kidney do not express the receptor. Conclusions Female Fischer 344 rat is an inexpensive reproducible and efficient preclinical model to study ovarian peritoneal carcinomatosis folate-targeted therapies.

Neuroimaging features and pathology of mixed glioblastoma--AVM complex: a case report.

This report is of a rare case of glioblastoma coexisting with an arteriovenous malformation in a 65-year-old man. Multimodal magnetic resonance imaging (MRI) performed at 3T revealed a necrotic and cystic lesion in the left hemisphere; morphological and metabolic findings were consistent with an infiltrating high-grade glioma, but the presence of dark vessel-like signals on T2* and susceptibility-weighted imaging (SWI) suggested the coexistence of a vascular malformation. The arteriovenous malformation was confirmed by MR angiography and cerebral angiography. The patient was operated on, and histological examination revealed atypical cells characteristic of glioblastoma multiforme and, in the same area, arteriovenous malformation. The possible role of angiogenic factors in this case is also addressed.