Variational multi-task MRI reconstruction: Joint reconstruction, registration and super-resolution.

Motion degradation is a central problem in Magnetic Resonance Imaging (MRI). This work addresses the problem of how to obtain higher quality, super-resolved motion-free reconstructions from highly undersampled MRI data. In this work, we present for the first time a variational multi-task framework that allows joining three relevant tasks in MRI: reconstruction, registration and super-resolution.

[Plastic arts workshop, in search of the therapeutic].

A plastic arts workshop makes no claims to provide therapeutic benefits. Patients are invited to attend without any clear objectives. This occupational activity soon becomes rooted in the care approach.

Haploid genetic screens identify genetic vulnerabilities to microtubule-targeting agents.

The absence of biomarkers to accurately predict anticancer therapy response remains a major obstacle in clinical oncology. We applied a genome-wide loss-of-function screening approach in human haploid cells to characterize genetic vulnerabilities to classical microtubule-targeting agents. Using docetaxel and vinorelbine, two well-established chemotherapeutic agents, we sought to identify genetic alterations sensitizing human HAP1 cells to these drugs.

Selected Alkylating Agents Can Overcome Drug Tolerance of G-like Tumor Cells and Eradicate BRCA1-Deficient Mammary Tumors in Mice.

We aimed to characterize and target drug-tolerant BRCA1-deficient tumor cells that cause residual disease and subsequent tumor relapse. We studied responses to various mono- and bifunctional alkylating agents in a genetically engineered mouse model for -mutant breast cancer. Because of the large intragenic deletion of the gene, no restoration of BRCA1 function is possible, and therefore, no BRCA1-dependent acquired resistance occurs.

Autonomously folded α-helical lockers promote RNAi.

RNAi is an indispensable research tool with a substantial therapeutic potential. However, the complete transition of the approach to an applied capability remains hampered due to poorly understood relationships between siRNA delivery and gene suppression. Here we propose that interfacial tertiary contacts between α-helices can regulate siRNA cytoplasmic delivery and RNAi.

Subunit composition of VRAC channels determines substrate specificity and cellular resistance to Pt-based anti-cancer drugs.

Although platinum-based drugs are widely used chemotherapeutics for cancer treatment, the determinants of tumor cell responsiveness remain poorly understood. We show that the loss of subunits LRRC8A and LRRC8D of the heteromeric LRRC8 volume-regulated anion channels (VRACs) increased resistance to clinically relevant cisplatin/carboplatin concentrations. Under isotonic conditions, about 50% of cisplatin uptake depended on LRRC8A and LRRC8D, but neither on LRRC8C nor on LRRC8E.

BRCA2-deficient sarcomatoid mammary tumors exhibit multidrug resistance.

Pan- or multidrug resistance is a central problem in clinical oncology. Here, we use a genetically engineered mouse model of BRCA2-associated hereditary breast cancer to study drug resistance to several types of chemotherapy and PARP inhibition. We found that multidrug resistance was strongly associated with an EMT-like sarcomatoid phenotype and high expression of the Abcb1b gene, which encodes the drug efflux transporter P-glycoprotein.

Risk of hormone escape in a human prostate cancer model depends on therapy modalities and can be reduced by tyrosine kinase inhibitors.

Almost all prostate cancers respond to androgen deprivation treatment but many recur. We postulated that risk of hormone escape--frequency and delay--are influenced by hormone therapy modalities. More, hormone therapies induce crucial biological changes involving androgen receptors; some might be targets for escape prevention.

Gene Expression Data to Mouse Atlas Registration Using a Nonlinear Elasticity Smoother and Landmark Points Constraints.

This paper proposes a numerical algorithm for image registration using energy minimization and nonlinear elasticity regularization. Application to the registration of gene expression data to a neuroanatomical mouse atlas in two dimensions is shown. We apply a nonlinear elasticity regularization to allow larger and smoother deformations, and further enforce optimality constraints on the landmark points distance for better feature matching.

Molecular profiling of patient-derived breast cancer xenografts.

Introduction: Identification of new therapeutic agents for breast cancer (BC) requires preclinical models that reproduce the molecular characteristics of their respective clinical tumors. In this work, we analyzed the genomic and gene expression profiles of human BC xenografts and the corresponding patient tumors.

Methods: Eighteen BC xenografts were obtained by grafting tumor fragments from patients into Swiss nude mice.

On the construction of topology-preserving deformation fields.

In this paper, we investigate a new method to enforce topology preservation on deformation fields. The method is composed of two steps. The first one consists in correcting the gradient vector fields of the deformation at the discrete level, in order to fulfill a set of conditions ensuring topology preservation in the continuous domain after bilinear interpolation.

Sugars comparable to glutathione as hemoglobin oxidation protectants during vacuum drying.

One of the most significant challenges to stabilization of blood in the dry state is mitigation of hemoglobin oxidation. Here, oxidation of free hemoglobin vacuum desiccated in phosphate-buffered saline alone reached 65%±5%. Arabinose, glucose, sucrose, trehalose, and raffinose at 100 mM were shown to reduce oxidation to 24%±2%, 23%±2%, 3%±1%, 8%±3%, and 7%±2%, respectively.

Modeling of response to endocrine therapy in a panel of human luminal breast cancer xenografts.

Resistance to endocrine therapy is a major complication of luminal breast cancer and studies of the biological features of hormonal resistance are limited by the lack of adequate preclinical models. The aim of this study is to establish and characterize a panel of primary human luminal breast carcinoma xenografts, and to evaluate their response to endocrine therapies. Four hundred and twenty-three tumor fragments obtained directly from patients have been grafted in the interscapular fatpad of Swiss nude mice.

Establishment and characterisation of a new breast cancer xenograft obtained from a woman carrying a germline BRCA2 mutation.

Background: The BRCA2 gene is responsible for a high number of hereditary breast and ovarian cancers, and studies of the BRCA2 biological functions are limited by the lack of models that resemble the patient's tumour features. The aim of this study was to establish and characterise a new human breast carcinoma xenograft obtained from a woman carrying a germline BRCA2 mutation.

Methods: A transplantable xenograft was obtained by grafting a breast cancer sample into nude mice.

A preclinical therapeutic schedule optimizing docetaxel plus estramustine administration in prostate cancer.

Androgen-dependent and castration-resistant prostate cancer (PC) is usually sensitive to docetaxel chemotherapy. Nevertheless, docetaxel resistance frequently appears after several cycles of treatment, raising the problem of salvage treatment for docetaxel-resistant PC patients. Although the combination of docetaxel and estramustine prolongs metastasis-free and overall survival of patients with androgen-independent PC, the use of this modality remains limited in elderly patients or patients with several comorbidities, especially vascular disease or gastrointestinal toxicity, because of unacceptable toxicity including venous thrombosis.

Hormone escape is associated with genomic instability in a human prostate cancer model.

Lack of hormone dependency in prostate cancers is an irreversible event that occurs through generation of genomic instability induced by androgen deprivation. Indeed, the cytogenetic profile of hormone-dependent (HD) prostate cancer remains stable as long as it received a hormone supply, whereas the profile of hormone-independent (HID) variants acquired new and various alterations. This is demonstrated here using a HD xenografted model of a human prostate cancer, PAC120, transplanted for 11 years into male nude mice and 4 HID variants obtained by surgical castration.

Self-repelling snakes for topology-preserving segmentation models.

The implicit framework of the level-set method has several advantages when tracking propagating fronts. Indeed, the evolving contour is embedded in a higher dimensional level-set function and its evolution can be phrased in terms of a Eulerian formulation. The ability of this intrinsic method to handle topological changes (merging and breaking) makes it useful in a wide range of applications (fluid mechanics, computer vision) and particularly in image segmentation, the main subject of this paper.

[New targeted therapies in hormone-refractory prostate cancer].

Although the number of men presenting with metastatic prostate cancer has decreased significantly over the last several years, the death rate for those men is essentially unchanged. Effective treatments have not existed for prostate cancer progressing after androgen deprivation therapy until recently. Docetaxel based chemotherapy has demonstrated to extend patient survival in two large randomized studies.

A new model of patient tumor-derived breast cancer xenografts for preclinical assays.

Purpose: To establish a panel of human breast cancer (HBC) xenografts in immunodeficient mice suitable for pharmacologic preclinical assays.

Experimental Design: 200 samples of HBCs were grafted into Swiss nude mice. Twenty-five transplantable xenografts were established (12.

Potentiation of antitumour activity of docetaxel by combination with trastuzumab in a human prostate cancer xenograft model and underlying mechanisms.

Antitumour activity of docetaxel (Taxotere) in hormone-dependent (HD) and hormone-independent (HID) prostate cancer PAC120 xenograft model was previously reported, and its level was associated with HER2 protein expression. In the present study, we evaluate the antitumour effects of docetaxel combined with trastuzumab (Herceptin), an anti-HER2 antibody. Although trastuzumab alone had no effect on tumour growth, it potentiated the antitumour activity of docetaxel in HD tumours and more strongly in HID variants.

Capacitation of fresh bovine spermatozoa on bovine epithelial oviduct cell monolayers.

Capacitation of fresh bovine spermatozoa on bovine epithelial oviduct cells was assessed1) by the ability of spermatozoa to fertilize bovine oocytes in vitro and2) by exposure to lysophosphatidylcholine (LC) to induce acrosome reaction in the capacitated spermatozoa. When spermatozoa were incubated on bovine epithelial oviduct cells in B2 medium supplemented with 10% estrous cow serum (ECS) and then exposed to 100 microg/ml LC for 15 minutes, the percentage of acrosome reaction induced increased in a time-dependent course, reaching a plateau after 6 hours. Inversely, when spermatozoa were incubated in B2+10% ECS alone, the percentage of acrosome reaction induced by LC didn't fluctuate.

In vitro fertilization of sheep oocytes matured in vivo.

Incubating washed ram spermatozoa in a modified Brackett's defined medium buffered with Hepes (DM-H) containing 20% of heat-inactivated sheep serum appears to be a reliable method of capacitating sperm for in vitro fertilization. Raising the Ca(++) concentration in the fertilization medium (DM-H-SS) to 10 mM stabilized the fertilization rate of various rams (2). This study was designed to determine if the developmental competence of the oocytes fertilized under such conditions was normal.