Automatic segmentation of blood cells from microscopic slides: A comparative analysis.

With the recent developments in deep learning, automatic cell segmentation from images of microscopic examination slides seems to be a solved problem as recent methods have achieved comparable results on existing benchmark datasets. However, most of the existing cell segmentation benchmark datasets either contain a single cell type, few instances of the cells, not publicly available. Therefore, it is unclear whether the performance improvements can generalize on more diverse datasets.

A comparative analysis of deep learning architectures on high variation malaria parasite classification dataset.

Malaria, one of the leading causes of death in underdeveloped countries, is primarily diagnosed using microscopy. Computer-aided diagnosis of malaria is a challenging task owing to the fine-grained variability in the appearance of some uninfected and infected class. In this paper, we transform a malaria parasite object detection dataset into a classification dataset, making it the largest malaria classification dataset (63,645 cells), and evaluate the performance of several state-of-the-art deep neural network architectures pretrained on both natural and medical images on this new dataset.

DNMTi/HDACi combined epigenetic targeted treatment induces reprogramming of myeloma cells in the direction of normal plasma cells.

Background: Multiple myeloma (MM) is the second most common hematologic malignancy. Aberrant epigenetic modifications have been reported in MM and could be promising therapeutic targets. As response rates are overall limited but deep responses occur, it is important to identify those patients who could indeed benefit from epigenetic-targeted therapy.

Automated and simplified identification of normal and abnormal plasma cells in Multiple Myeloma by flow cytometry.

Background: Multiple myeloma (MM) is an incurable disease characterized by clonal plasma cell (PC) proliferation within the bone marrow (BM). Next-generation flow cytometry has become the reference tool to follow minimal residual disease (MRD). We developed a new simpler and cheaper flow cytometry method to analyze bone marrow samples in patients with MM.

Central Nervous System and Peripheral Inflammatory Processes in Alzheimer's Disease: Biomarker Profiling Approach.

Brain inflammation is one of the hallmarks of Alzheimer disease (AD) and a current trend is that inflammatory mediators, particularly cytokines and chemokines, may represent valuable biomarkers for early screening and diagnosis of the disease. Various studies have reported differences in serum level of cytokines, chemokines, and growth factors in patients with mild cognitive impairment or AD. However, data were often inconsistent and the exact function of inflammation in neurodegeneration is still a matter of debate.

Drug metabolism and clearance system in tumor cells of patients with multiple myeloma.

Resistance to chemotherapy is a major limitation of cancer treatments with several molecular mechanisms involved, in particular altered local drug metabolism and detoxification process. The role of drug metabolism and clearance system has not been satisfactorily investigated in Multiple Myeloma (MM), a malignant plasma cell cancer for which a majority of patients escapes treatment. The expression of 350 genes encoding for uptake carriers, xenobiotic receptors, phase I and II Drug Metabolizing Enzymes (DMEs) and efflux transporters was interrogated in MM cells (MMCs) of newly-diagnosed patients in relation to their event free survival.

GenomicScape: an easy-to-use web tool for gene expression data analysis. Application to investigate the molecular events in the differentiation of B cells into plasma cells.

DNA microarrays have considerably helped to improve the understanding of biological processes and diseases. Large amounts of publicly available microarray data are accumulating, but are poorly exploited due to a lack of easy-to-use bioinformatics resources. The aim of this study is to build a free and convenient data-mining web site (www.

Preclinical efficacy of sepantronium bromide (YM155) in multiple myeloma is conferred by down regulation of Mcl-1.

The inhibitor-of-apoptosis family member survivin has been reported to inhibit apoptosis and regulate mitosis and cytokinesis. In multiple myeloma, survivin has been described to be involved in downstream sequelae of various therapeutic agents. We assessed 1093 samples from previously untreated patients, including two independent cohorts of 392 and 701 patients, respectively.

A DNA repair pathway score predicts survival in human multiple myeloma: the potential for therapeutic strategy.

DNA repair is critical to resolve extrinsic or intrinsic DNA damage to ensure regulated gene transcription and DNA replication. These pathways control repair of double strand breaks, interstrand crosslinks, and nucleotide lesions occurring on single strands. Distinct DNA repair pathways are highly inter-linked for the fast and optimal DNA repair.

In vitro infection of primary human hepatocytes by HCV-positive sera: insights on a highly relevant model.

Objective: Adult primary human hepatocytes (PHHs) support the complete infection cycle of natural HCV from patients' sera. The molecular details underlying sera infectivity towards these cells remain largely unknown. Therefore, we sought to gain a deeper comprehension of these features in the most physiologically relevant culture system.

DNA repair pathways in human multiple myeloma: role in oncogenesis and potential targets for treatment.

Every day, cells are faced with thousands of DNA lesions, which have to be repaired to preserve cell survival and function. DNA repair is more or less accurate and could result in genomic instability and cancer. We review here the current knowledge of the links between molecular features, treatment, and DNA repair in multiple myeloma (MM), a disease characterized by the accumulation of malignant plasma cells producing a monoclonal immunoglobulin.

Gene expression-based prediction of myeloma cell sensitivity to histone deacetylase inhibitors.

Background: Multiple myeloma (MM) is still a fatal plasma cell cancer. Novel compounds are currently clinically tested as a single agent in relapsing patients, but in best cases with partial response of a fraction of patients, emphasising the need to design tools predicting drug efficacy. Histone deacetylase inhibitors (HDACi) are anticancer agents targeting epigenetic regulation of gene expression and are in clinical development in MM.

A Molecular Predictor Reassesses Classification of Human Grade II/III Gliomas.

Diffuse gliomas are incurable brain tumors divided in 3 WHO grades (II; III; IV) based on histological criteria. Grade II/III gliomas are clinically very heterogeneous and their prognosis somewhat unpredictable, preventing definition of appropriate treatment. On a cohort of 65 grade II/III glioma patients, a QPCR-based approach allowed selection of a biologically relevant gene list from which a gene signature significantly correlated to overall survival was extracted.

Inhibition of DEPDC1A, a bad prognostic marker in multiple myeloma, delays growth and induces mature plasma cell markers in malignant plasma cells.

High throughput DNA microarray has made it possible to outline genes whose expression in malignant plasma cells is associated with short overall survival of patients with Multiple Myeloma (MM). A further step is to elucidate the mechanisms encoded by these genes yielding to drug resistance and/or patients' short survival. We focus here on the biological role of the DEP (for Disheveled, EGL-10, Pleckstrin) domain contained protein 1A (DEPDC1A), a poorly known protein encoded by DEPDC1A gene, whose high expression in malignant plasma cells is associated with short survival of patients.

Tumor cells in multiple myeloma patients inhibit myeloma-reactive T cells through carcinoembryonic antigen-related cell adhesion molecule-6.

Although functionally competent cytotoxic, T cells are frequently observed in malignant diseases, they possess little ability to react against tumor cells. This phenomenon is particularly apparent in multiple myeloma. We here demonstrate that cytotoxic T cells reacted against myeloma antigens when presented by autologous dendritic cells, but not by myeloma cells.

Modeling risk stratification in human cancer.

Motivation: Despite huge prognostic promises, gene expression-based survival assessment is rarely used in clinical routine. Main reasons include difficulties in performing and reporting analyses and restriction in most methods to one high-risk group with the vast majority of patients being unassessed. The present study aims at limiting these difficulties by (i) mathematically defining the number of risk groups without any a priori assumption; (ii) computing the risk of an independent cohort by considering each patient as a new patient incorporated to the validation cohort and (iii) providing an open-access Web site to freely compute risk for every new patient.

Development of gene expression-based score to predict sensitivity of multiple myeloma cells to DNA methylation inhibitors.

Multiple myeloma is a plasma cell cancer with poor survival, characterized by the clonal expansion of multiple myeloma cells (MMC), primarily in the bone marrow. Novel compounds are currently tested in this disease, but partial or minor patients' responses are observed for most compounds used as a single agent. The design of predictors for drug efficacy could be most useful to better understand basic mechanisms targeted by these drugs and design clinical trials.

Identification of pluripotent and adult stem cell genes unrelated to cell cycle and associated with poor prognosis in multiple myeloma.

Gene expression-based scores used to predict risk in cancer frequently include genes coding for DNA replication, repair or recombination. Using two independent cohorts of 206 and 345 previously-untreated patients with Multiple Myeloma (MM), we identified 50 cell cycle-unrelated genes overexpressed in multiple myeloma cells (MMCs) compared to normal human proliferating plasmablasts and non-proliferating bone marrow plasma cells and which have prognostic value for overall survival. Thirty-seven of these 50 myeloma genes (74%) were enriched in genes overexpressed in one of 3 normal human stem cell populations--pluripotent (18), hematopoietic (10) or mesenchymal stem cells (9)--and only three genes were enriched in one of 5 populations of differentiated cells (memory B lymphocytes, T lymphocytes, polymorphonuclear cells, monocytes, osteoclasts).

Clinical and prognostic role of annexin A2 in multiple myeloma.

Annexin A2 (ANXA2) promotes myeloma cell growth, reduces apoptosis in myeloma cell lines, and increases osteoclast formation. ANXA2 has been described in small cohorts of samples as expressed by myeloma cells and cells of the BM microenvironment. To investigate its clinical role, we assessed 1148 samples including independent cohorts of 332 and 701 CD138-purified myeloma cell samples from previously untreated patients together with clinical prognostic factors, chromosomal aberrations, and gene expression-based high-risk scores, along with expression of ANXA2 in whole BM samples, stromal cells, osteoblasts, osteoclasts, and BM sera.

The role of fluorescence in situ hybridization and gene expression profiling in myeloma risk stratification.

Multiple myeloma patients' survival under treatment varies from a few months to more than 15 years. Clinical prognostic factors, especially beta2-microglobulin (B2M) and the international staging system (ISS), allow risk assessment to a certain extent, but do not identify patients at very high risk. As malignant plasma cells are characterized by a variety of chromosomal aberrations and changes in gene expression, a molecular characterization ofCD138-purified myeloma cells by interphase fluorescence in situ hybridization (iFISH) and gene expression profiling (GEP) can be used for improved risk assessment, iFISH allows a risk stratification with presence of a translocation t(4;14) and/or deletion of 17p13 being the best documented adverse prognostic factors.

Genes with a spike expression are clustered in chromosome (sub)bands and spike (sub)bands have a powerful prognostic value in patients with multiple myeloma.

Background: Genetic abnormalities are common in patients with multiple myeloma, and may deregulate gene products involved in tumor survival, proliferation, metabolism and drug resistance. In particular, translocations may result in a high expression of targeted genes (termed spike expression) in tumor cells. We identified spike genes in multiple myeloma cells of patients with newly-diagnosed myeloma and investigated their prognostic value.

Gene expression profiling in multiple myeloma--reporting of entities, risk, and targets in clinical routine.

Purpose: Multiple myeloma is an incurable malignant plasma cell disease characterized by survival ranging from several months to more than 15 years. Assessment of risk and underlying molecular heterogeneity can be excellently done by gene expression profiling (GEP), but its way into clinical routine is hampered by the lack of an appropriate reporting tool and the integration with other prognostic factors into a single "meta" risk stratification.

Experimental Design: The GEP-report (GEP-R) was built as an open-source software developed in R for gene expression reporting in clinical practice using Affymetrix microarrays.

Characterization of a transitional preplasmablast population in the process of human B cell to plasma cell differentiation.

The early steps of differentiation of human B cells into plasma cells are poorly known. We report a transitional population of CD20(low/-)CD38(-) preplasmablasts along differentiation of human memory B cells into plasma cells in vitro. Preplasmablasts lack documented B cell or plasma cell (CD20, CD38, and CD138) markers, express CD30 and IL-6R, and secrete Igs at a weaker level than do plasmablasts or plasma cells.

Gene expression profile of ADAMs and ADAMTSs metalloproteinases in normal and malignant plasma cells and in the bone marrow environment.

Objective: The ADAM (a disintegrin and metalloproteinases) and the related ADAMTS (a disintegrin and metalloproteinases with thrombospondin) motifs metalloproteinases are membrane-anchored and secreted proteins exhibiting key roles in mediating cell adhesion, proteolytic shedding, and cell signaling. Dysregulation of these proteins has been observed in some pathologic states, including cancers. Their contribution to multiple myeloma, a plasma-cell neoplasia strongly dependent on bone marrow environment, has been poorly characterized.

A high-risk signature for patients with multiple myeloma established from the molecular classification of human myeloma cell lines.

Background: Multiple myeloma is a plasma-cell tumor with heterogeneity in molecular abnormalities and treatment response.

Design And Methods: We have assessed whether human myeloma cell lines have kept patients' heterogeneity using Affymetrix gene expression profiling of 40 human myeloma cell lines obtained with or without IL6 addition and could provide a signature for stratification of patient risk.

Results: Human myeloma cell lines, especially those derived in the presence of IL6, displayed a heterogeneity that overlaps that of the patients with multiple myeloma.