MicroRNAs control the differentiation and function of B cells, which are considered key elements in the pathogenesis of systemic lupus erythematosus (SLE). However, a common micro(mi)RNA signature has not emerged since published data includes patients of variable ethnic background, type of disease, and organ involvement, as well as heterogeneous cell populations. Here, we aimed at identifying a miRNA signature of purified B cells from renal and non-renal severe SLE patients of Latin American background, a population known to express severe disease. Genome-wide miRNA expression analyses were performed on naive and memory B cells and revealed two categories of miRNA signatures. The first signature represents B cell subset-specific miRNAs deregulated in SLE: 11 and six miRNAs discriminating naive and memory B cells of SLE patients from healthy controls (HC), respectively. Whether the miRNA was up or down-regulated in memory B cells as compared with naive B cells in HC, this difference was abolished in SLE patients, and vice versa. The second signature identifies six miRNAs associated with specific pathologic features affecting renal outcome, providing a further understanding for SLE pathogenesis. Overall, the present work provided promising biomarkers in molecular diagnostics for disease severity as well as potential new targets for therapeutic intervention in SLE.
Papillary breast lesions are rare breast tumors that comprise a broad spectrum of diseases. Pathologically they present as mass-like projections attached to the wall of the ducts, supported by fibrovascular stalks lined by epithelial cells. On mammogram they appear as masses that can be associated with microcalcifications. Ultrasound is the most used imaging modality. On ultrasound papillary lesions appear as homogeneous solid lesions or complex intracystic lesions. A nonparallel orientation, an echogenic halo or posterior acoustic enhancement associated with microcalcifications are highly suggestive of malignancy. MRI has proven to be useful to establish the extent of the lesion. Core needle biopsy is the gold standard for diagnosis. Surgical excision is usually recommended, although treatment for papillomas without atypia is still controversial.
Background and objectives Several microRNAs are known to control the differentiation and function of B cells, that are considered key elements in the pathogenesis of systemic lupus erythematosus (SLE). However, a common miRNA signature has not emerged in SLE, since published data includes patients of variable ethnic background, type of disease and organ involvement. Moreover, published gene expression studies are often limited since they target only unfractionated, heterogeneous cell populations. Here, we aimed at identifying a miRNA-signature of purified B cells from renal and non renal severe (Bilag A) SLE patients of hispanic ethnic background, a population know to express severe disease. Materials and methods Blood samples were obtained from healthy sex, age and ethnically matched controls (HC) with no history of autoimmune diseases and from SLE patients of chilean hispanic descent fulfilling SLICC and ACR criteria, with or without severe lupus nephritis (LN) (mean Bilag count respectively 17.8 and 16.8). Naive and memory B cells were sorted using CD27 surface marker. Total RNAs extraction, reverse transcription, and amplification steps were performed to fulfil quality and integrity criteria of the MIQE guidelines. The genome-wide miRNA expression study was perfomed using the TaqMan® Human MicroRNA Array Cards v3.0 (Applied Biosystems). Data were normalised using ExpressionSuite software (Life technologies) and analysed using RT2 profiler PCR array data analysis version 3.5 (Qiagen). Results TLDA analyses of naive and memory B cells from HC and 2 subsets of SLE patients revealed two categories of miRNA-based signatures. The first signature represents miRNAs with potential as diagnostic biomarkers : 11 miRNAs discriminating all SLE patients from HC, and 8 miARNs discriminating patient subsets (SLE versus SLE-LN). The second signature identifies 13 miRNAs with therapeutic potential in lupus. Clustering analyses of TLDA datasets evidenced that the main differences in miRNA expression profilings between SLE patients were between naive and memory B cells, independently of disease severity. In all cases, whether the miRNA was up or down-regulated in memory B cells as compared with naive B cells in HC, this difference was abolished in SLE patients. Among these, we found miR-223 that was previously reported as deregulated in SLE, as well as in other autoimmune disorders and B cell leukaemia. Array data were further validated on individual samples (n = 6). Conclusions Overall, the present work identified two types of miRNA-based signatures in circulating B cells isolated from Chilean SLE patients, providing promising biomarkers in molecular diagnostics for disease severity as well as potential new targets for therapeutic intervention in SLE. References Wu HJ, Ivanov II, Darce J, et al. Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells. Immunity 2010; 32(6):815–27. doi: 10.1016/j.immuni.2010.06.001. Lécuyer E, Rakotobe S, Lengliné-Garnier H, et al. Segmented fil...
Ovarian cancer patients respond well to first line chemotherapy but present high incidences of toxicity followed by consistent relapse within 18 months. Despite every cancer and patient being unique, generally all cancers are treated by the same chemotherapy regimes and patient metabolism is not considered in treatment selection. Differing metabolism may account for unacceptable toxicity or failures in chemotherapy treatment. It is becoming accepted that the metastatic cell is distinct to those found in the primary tumor and is thus the true target of chemotherapy. Our objectives were to isolate these potential ovarian metastatic cells from patients and correlate their in vitro response to the chemotherapy with clinical response. The single nucleotide polymorphism (SNP) distribution of genes related to chemotherapy metabolism was also analyzed in each patient. Primary cultures and blood samples of ovarian patients were obtained with signed informed consent from a network of Chilean and Peruvian hospitals. Chemotherapy response was assessed by MTS and data correlated with medical follow-up. SNPs were detected using commercial taqman probes from Applied Biosystem. Results. Ovarian cancer patients with clinical follow-up demonstrated a marked separation of progression free survival (PFS) curves according to classification within our in vitro assay. Analysis of exclusively first line patients demonstrated a median PFS of 17 months for patients predicted to respond to treatment showed by our assay, but only an average of 2 months of PFS in patients that the assay predicted no response. Initial analysis of 14 SNPs related to paclitaxel-platinum based chemotherapy demonstrates marked differences in Chilean patients. Conclusion. We demonstrate a clear distinction in time to relapse between the patients predicted or not to respond to treatment by our assay. Ovarian cancer patients demonstrate notably different distributions in SNPs previously correlated with platinum metabolism. Our results highlight the requirement of the medical community to take this research to the stage of randomized clinical trials. CORFO 13CTI21526-P6 & 13IDL2-18608, FONDECYT 1140960, 1140657 & 1120292. Citation Format: Maria Loreto Bravo, Pamela Gonzalez, Sumie Kato, Carolina Ibañez, Marcelo Garrido, Jorge Brañes, Maria Isabel Barriga, Eva Bustamante, Nicanor Barrena, Catalina Alonso, Leonel Muñoz, Erasmo Bravo, Clemente Arab, Alejandro Barra, Paula Jimenez, Patricio Gayan, Fernando Gonzalez, Ignacio Chavez, Alfredo Aguilar, Joseph Pinto, Mauricio Cuello, Gareth Owen, Jaime Cartagena. Prediction of chemotherapy response and metabolism for the tailoring of ovarian cancer treatment. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4314. doi:10.1158/1538-7445.AM2015-4314
This work is licensed under Creative Commons Attribution 4.0 License AJBSR.MS.ID.001160.
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