Search

Dupilumab is a biologic, acting on IL-4 and IL-13 pathways. Dupilumab has a pediatric indication for treating severe asthma and atopic dermatitis. We report a pediatric case concerning paucisymptomatic, transient, and self-resolving hyperthyroidism. The updated literature includes the case of an adult patient who reported with hyperthyroidism, which was transient and self-resolving. Despite that these cases were transient and self-resolving, we would suggest that thyroid function assessment could be included in the follow-up of patients treated with Dupilumab. Dupilumab discontinuation is not required pending endocrinological assessment, mainly if there is an optimal clinical response to the biologic.

Introdução: A hanseníase é uma doença infectocontagiosa, que devido às repercussões clínicas e aos dados epidemiológicos é considerada de notificação compulsória. Contudo, esse transtorno quando é precocemente identificado e adequadamente manejado, evita consideravelmente o círculo vicioso de contágio e as manifestações clínicas que tornam a doença tão alvo de estigma. Objetivo: Descrever a reação negativa oriunda da poliquimioterapia imposta na hanseníase. Metodologia: Trata-se de uma revisão narrativa de literatura, fundamentada nas plataformas do Scielo, Pubmed, Lilacs e demais literaturas pertinentes ao tema, utilizando-se os seguintes descritores: Reação Hansênica, Efeitos Adversos e Poliquimioterapia, no período de janeiro de 2023. Resultados e Discussão: Atualmente, o protocolo terapêutico voltado para a Hanseníase é a poliquimioterapia e possui boa eficácia e tolerância pela maioria dos pacientes. No advém, a minoria destes apresenta reações adversas que variam de leve a exacerbadas e que devem ser devidamente classificados e orientados para outras opções farmacológica, objetivando impedir que o paciente abandone o tratamento, junto às enormes repercussões oriundas deste, e propiciar melhor qualidade de vida. Conclusão: Estima-se que o tratamento da Hanseníase é algo importante e indispensável para evitar problemas de saúde pública, mas este se baseia em uma alta carga associada de remédios potentes, a qual alguns portadores possuem sensibilidade e se orientados, podem continuar o tratamento até o alcance da cura.

Advanced hybrid closed loop (AHCL) systems are the newest tool to improve metabolic control in type 1 diabetes (T1D). Long-term glycemic control of children and adolescents with T1D switching to MiniMed™ 780G in a real clinical setting was evaluated.Time in range (TIR) and in different glucose ranges, glycemic variability indexes, HbA1c and basal-bolus insulin distribution were evaluated in 44 subjects (mean age 14.2 ± 4.0 years, 22 males) during manual mode period, first 14 days (A14d) and first month after auto-mode activation (A1M), first 14 days after 3 months (A3M) and 6 months (A6M) in auto-mode.Mean TIR at A14d was 76.3 ± 9.6% versus 69.3 ± 12.6% in manual mode (p 0.001), and this improvement was maintained over 6 months. Subjects with TIR70% and80% in manual mode were 45% and 23%, respectively, and increased to 80% (p = 0.041) and 41% (p = 0.007) at A14d. Basal-bolus distribution changed in favor of bolus, and auto-correction boluses inversely correlated with TIR. HbA1c was 7.2 ± 0.7% (55 mmol/mol) at baseline and significantly improved after 3 months (6.7 ± 0.5%, 50 mmol/mol, p 0.001) and 6 months (6.6 ± 0.5%, 49 mmol/mol, p 0.001). TIR was higher in individuals13 years at all time periods (p 0.001). Glycemic target120 mg/dl was associated with better TIR.AHCL MiniMed™ 780G allowed rapid and sustained improvement of glycemic control in young T1D patients, reaching recommended TIR. Teenagers showed good technology adherence with optimal TIR, maintained better over time compared to younger children. Stricter settings were associated with better metabolic control, without increase in severe hypoglycemia occurrence.

Impact investing is progressively losing focus in ensuring investments really do make a difference; therefore, the growth of the market may not make real social and environmental change. We propose three ways to put the “impact” back into the heart of impact investment.

Emery-Dreifuss muscular dystrophy (EDMD) is a rare disease characterized by early contractures, progressive muscle weakness, and cardiac abnormalities. Different subtypes of EDMD have been described, with the two most common forms represented by the X-linked EDMD1, caused by mutations in the EMD gene encoding emerin, and the autosomal EDMD2, due to mutations in the LMNA gene encoding lamin A/C. A clear definition of the magnetic resonance imaging (MRI) pattern in the two forms, and especially in the rarer EDMD1, is still lacking, although a preferential involvement of the medial head of the gastrocnemius has been suggested in EDMD2. We report a 13-year-old boy with mild limb girdle muscle weakness, elbow and ankle contractures, with absence of emerin at muscle biopsy, carrying a hemizygous frameshift mutation on the EMD gene (c.153dupC/p.Ser52Glufs*9) of maternal inheritance. Minor cardiac rhythm abnormalities were detected at 24-hour Holter electrocardiogram and required β-blocker therapy. MRI scan of the thighs showed a mild diffuse involvement, while tibialis anterior, extensor digitorum longus, peroneus longus, and medial gastrocnemius were the most affected muscles in the leg. We also provide a review of the muscular MRI data in EDMD patients and highlight the relative heterogeneity of the MRI patterns found in EDMDs, suggesting that muscle MRI should be studied in larger EDMD cohorts to better define disease patterns and to cover the wide disease spectrum.

The file contains the list and information of all antibodies used in the study

PDF file 1045K, Merged file (pdf) including methods, figures and legends

PDF file 45K, List of data sets and case sconsidered for human GEP analysis

Supplementary Figure 1. Representative plots illustrating analysis of tumor-specific CD8+ T cell response in TRAMP and KitWsh-TRAMP mice. Supplementary Figure 2. CD8+T cells from PDLN and prostates of KitWsh-TRAMP mice are responsive. Supplementary Figure 3. Quantification of MCs or T cells after reconstitution of depletion, respectively. Supplementary Figure 4. Flow cytometry identification of T cells in spleen and prostate of TRAMP and KitWsh-TRAMP mice. Supplementary Figure 5. Flow cytometry identification of myeloid cells in spleen and prostate of TRAMP and KitWsh-TRAMP mice. Supplementary Figure 6. MCs and PMN-MDSC can interact via CD40L-CD40 in TRAMP mice. Supplementary Figure 7. Wild type and CD40L-/- BMMC are equally functional, but CD8+T cells from PDLN and prostates of KitWsh-TRAMP mice reconstituted with BMMC CD40L-/- are still responsive. Supplementary Figure 8. MCs, CD40L and CD33 co-localize in human tumor prostate cancer samples. Supplementary Figure 9. Correlation between MC-genes and MDSC-activity genes in human prostate cancer data sets. Supplementary Figure 10. MC/PMN-MDSC signatures outperform random signatures of the same length.

XLS file 1816K, Biological programs over-represented in the SPARC-related signature

Immunotherapy, including the use of checkpoint inhibitors, is a potent therapeutic approach for some cancers, but has limited success with prostate tumors, in which immune suppression is instigated by the tumor. The immunosuppressive capacity of mast cells, which promote adenocarcinoma development in the prostate, prompted our investigation on whether mast cells promote tolerance to SV40 Large-T antigen, the transforming oncogene in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice. The incidence of adenocarcinoma was reduced in the offspring of a cross between TRAMP mice and mast cell–deficient KitWsh mice. TRAMP mice are tolerant to the SV40 Large T antigen, which is otherwise immunogenic in normal syngeneic B6 mice. Genetic ablation of mast cells in TRAMP mice restored their ability to mount a tumor-specific cytotoxic T-cell response. In KitWsh-TRAMP mice, the restored T-cell immunity correlated with the reduced activity of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC), along with their reduced expression of Arg1, Nos2, and Stat3. Having found that CD40L-expressing mast cells can interact in vivo with CD40-expressing PMN-MDSC, we then determined that only KitWsh-TRAMP mice reconstituted with mast cells expressing CD40L could restore PMN-MDSCs suppressive functions, T-cell unresponsiveness and adenocarcinoma development. Thus, mast cells have an immunoregulatory effect on PMN-MDSCs activity through CD40L-CD40 interaction, favoring immunosuppression and tumor onset. In prostate cancer patients, in silico analyses correlated poor clinical outcomes with high expression of genes related to mast cells and PMN-MDSCs. Cancer Immunol Res; 6(5); 552–65. ©2018 AACR.

PDF file 62K, List of inflammatory up and down modulated genes in SPARC high human B-NHLs

The file contains the lists of MC and MDSC related genes

Sunto Gli incentivi fiscali riguardo le ristrutturazioni immobiliari, le opere volte alla riduzione del rischio sismico e quelle per il miglioramento dell’efficienza energetica, costituiscono una spinta significativa del legislatore per il miglioramento della sicurezza, dell’efficienza energetica degli edifici, nonché, non da ultimo, del loro aspetto architettonico. L’aggiunta di ulteriori facilitazioni, quali lo sconto in fattura e la cessione del credito d’imposta, sono uno sforzo ulteriore volto a promuovere un loro maggior impiego. Nel fondo in trust, sovente, sono apportati immobili e l’accesso agli incentivi pone condizioni soggettive diverse in base alla disposizione che si esamina. Ciò richiede un’analisi critica di tutte le facilitazioni fiscali proposta dal legislatore, nel caso che gli immobili siano in differente modo apportati al fondo in trust e si intenda fruire delle agevolazioni in parola. Non ci proponiamo di analizzare specificamente i vantaggi fiscali sulle ristrutturazioni, il risparmio energetico ed il rischio sismico in quanto tali, temi che peraltro sono ampiamente dibattuti anche attualmente e su cui è stato e si continua a scrivere molto e che sono altresì in continuo aggiornamento dal lato normativo e della prassi, ma di individuare se, quando e come, gli immobili apportati nel fondo di un trust interno non commerciale – d’ora in avanti solo trust – possono godere di quale dato premio fiscale. Tuttavia questo ci obbliga comunque a dare un quadro almeno sintetico ma aggiornato, riguardo ogni facilitazione.

In the wake of the Covid-19 pandemic, public private partnerships (PPP) can prove useful to close the healthcare investment gap and accelerate long-term recovery, by matching public and private money. Despite their extensive application in the delivery of major infrastructure projects globally, their performance remains contested. Drawing on a unique set of data of PPP contracts for healthcare investments in Italy, the paper explores the antecedents (namely, policies, institutions, and contracts), that have influenced the capacity of PPP contracts to deliver performance, measured in terms of value for money (VfM), and contract stability. Results show that although explicit policy goals have a clear contribution, VfM can benefit from competent central PPP institutions, which should play a hands-on role in the planning, design, and project management activities. At the same time, centralised PPP units, if not combined with local competent authorities and strong governance mechanisms, may increase the risk of contract renegotiation.

In recent decades, interest in sustainable food packaging systems with additional functionality, able to increase the shelf life of products, has grown steadily. Following this trend, the present review analyzes the state of the art of this active renewable packaging. The focus is on antimicrobial systems containing nanocellulose and chitosan, as support for the incorporation of essential oils. These are the most sustainable and readily available options to produce completely natural active packaging materials. After a brief overview of the different active packaging technologies, the main features of nanocellulose, chitosan, and of the different essential oils used in the field of active packaging are introduced and described. The latest findings about the nanocellulose- and chitosan-based active packaging are then presented. The antimicrobial effectiveness of the different solutions is discussed, focusing on their effect on other material properties. The effect of the different inclusion strategies is also reviewed considering both in vivo and in vitro studies, in an attempt to understand more promising solutions and possible pathways for further development. In general, essential oils are very successful in exerting antimicrobial effects against the most diffused gram-positive and gram-negative bacteria, and affecting other material properties (tensile strength, water vapor transmission rate) positively. Due to the wide variety of biopolymer matrices and essential oils available, it is difficult to create general guidelines for the development of active packaging systems. However, more attention should be dedicated to sensory analysis, release kinetics, and synergetic action of different essential oils to optimize the active packaging on different food products. © 2022 The Authors. Journal of The Science of Food and Agriculture published by John WileySons Ltd on behalf of Society of Chemical Industry.

Electrolyte-Gated Organic Field-Effect Transistors (EGOFETs) offer many opportunities for the development of low-cost and low-power electronics suitable for applications like sensors and point-of-care tests; however, EGOFETs can be affected by the drift of their operative point that causes signals distortion and loss of information during sensing applications. Here, a blend of 2,8-Difluoro-5,11-bis(triethylsilylethynyl)anthradithiophene (diF-TES-ADT) and polystyrene (PS) is used as the active material for the fabrication of dual-gate EGOFETs. We exploited the dual-gate architecture to improve EGOFETs stability by implementing digital feedback that uses the back-gate electrode to compensate dynamically for the transistor threshold voltage allowing us to fix its operative point for prolonged tests (>10 h) with different aqueous solutions (Milli-Q water, NaCl 0.1 M and a physiological solution). The presented real-time threshold voltage compensation does not only allow to steady EGOFETs DC output current, but it also preserves EGOFETs sensing capability for the detection of signals with frequencies as low as 1 Hz., The research leading to these results has received funding from the University of Padua, Department of Chemical Sciences (Grants: P-DISC#09BIRD2019-UNIPD - SMOW -; P-DiSC#11NExuS_BIRD2020-UNIPD - CARBON-FET -). It is further funded by the Italian Ministry of Education, Universities and Research through the project entitled “Nanochemistry for Energy and Health, NExuS” (the national funding network termed “Dipartimenti di Eccellenza” awarded to the Department of Chemical Sciences at the University of Padua). This work was partially supported by the University of Padua, Department of Information Engineering, under the initiative Project PROACTIVE 2018, and by MIUR (Italian Minister for Education) under the initiative “Departments of Excellence” (Law 232/2016). This work was funded by the Spanish Ministry of Science and Innovation with the project GENESIS PID2019-111682RB-I00 and through the “Severo Ochoa” Programme for Centers of Excellence in R&D (FUNFUTURE CEX2019-000917-S), and the Generalitat de Catalunya (2017-SGR-918). S. R. acknowledges her FPI fellowship and is enrolled in the UAB PhD program., With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000917-S).

Two vaccines against SARS-CoV-2 are approved by the World Health Organization (WHO) for minors aged 12 years and over. Currently, people with both type 1 diabetes (T1D) and type 2 diabetes (T2D) are prioritized for vaccination.To evaluate possible glycemic control modification, insulin dose adjustment and adverse effects after COVID-19 vaccination in young T1D individuals, users of different technology levels.Thirty-nine T1D individuals, who received a whole vaccination cycle of either Moderna or Pfizer- BioNTech vaccines, were enrolled, 24 of whom using advanced hybrid closed loop systems (AHCLs) and 15 using intermittently scanned continuous glucose monitoring (isCGM). Symptoms after each dose and the following variables were considered: time in range 70-180 mg/dl (TIR), time in different glucose ranges, mean glucose levels, coefficient of variation (CV), total daily dose (TDD) and bolus proportion RESULTS: No significant differences in TIR, time in different glucose ranges, mean glucose levels, TDD, bolus proportion, were observed before and after any dose nor before and after the whole vaccination cycle. CV was significantly lower after the whole vaccination cycle (CV pre-vaccination 35.1 ± 6.9% vs. CV post-vaccination 33.5 ± 6.3%; p 0.031) in subjects treated by AHCLs. Side effects after the vaccination were mild and more frequent after the second dose. No severe adverse reactions were reported.COVID-19 vaccination was safe and not associated with significant perturbation of glycemic control in adolescents and young adults with T1D. This information could be of clinical use when counseling families about SARS-CoV-2 vaccination in young people with T1D.

South-Eastern Spain is a key locality of the Western Mediterranean to unravel the origin of post-collisional magmatism and its relationships with the multi-stage evolution of the upper mantle in complex geodynamic settings. This study is focused on the Plio-Pleistocene post-collisional intraplate-like alkali basalts cropping out in the Tallante area (South-Eastern Spain) that are erupted in a region previously characterised by subduction related calc-alkaline to ultrapotassic (i.e., lamproitic) volcanism. Tallante alkali basalts represent a volcanic episode similar to other contemporary small volume intraplate volcanic occurrences of Western-Central Europe and North Africa, which are believed to derive from a Common Mantle Reservoir characterising the entire Circum Mediterranean asthenosphere. We report new major, trace element, and Sr-Nd-Pb isotope data on Tallante alkali basalts, showing compositions broadly similar to the other mafic volcanic rocks derived from the Common Mantle Reservoir and thus suggesting an asthenospheric component similar to other European within plate volcanic rocks. On the other hand, specific trace element ratios, such as Ce/Pb, Nb/U, Th/Yb, along with delta207Pb/204Pb and 87Sr/86Sr, clearly indicate the involvement of an enriched, subduction-related component, with a lamproitic geochemical and isotopic flavour. The trace element ratios suggest that low melting degree magmas from the Common Mantle Reservoir infiltrated and triggered melting of the strongly metasomatised sub-continental lithospheric mantle, which produced the lamproitic magmas previously erupted in the same area. The proposed origin of Tallante alkali basalts, located along a large scale left-lateral strike-slip fault, is consistent with analytical, numerical and laboratory models indicating that narrow subduction zones such as the Gibraltar Arc are characterised by mantle inflow around the slab edges determining upwelling and adiabatic melting of the asthenospheric mantle through slab tears.

Supplementary Figure Legend from Antimitotic effect of the retinoid 4-oxo-fenretinide through inhibition of tubulin polymerization: a novel mechanism of retinoid growth–inhibitory activity

Supplementary Figure S4. PDGFRbeta identifies vascular lacunae in TNBC tissues

Supplementary Results and Supplementary Table S1.

Supplementary Figure legends (S1-S4)

Purpose: The aim of this study was to analyze receptor tyrosine kinases (RTK) and their downstream signaling activation profile in myxoid liposarcomas (MLS) by investigating 14 molecularly profiled tumors: 7 naive and 7 treated with conventional chemotherapy/radiotherapy or the new drug trabectedin.Experimental Design: Frozen and matched formalin-fixed, paraffin-embedded material from surgical specimens were analyzed using biochemical, molecular, and molecular/cytogenetic approaches, complemented by immunohistochemistry and confocal microscopy.Results: In the absence of any RTK and downstream effector deregulation, the naive cases revealed epidermal growth factor receptor, platelet-derived growth factor receptor B, RET, and MET activation sustained by autocrine/paracrine loops, and RTK cross-talk as a result of heterodimerization. Interestingly, RET and MET activation seems to play a major role in the pathogenesis of MLS by involving different targets through different mechanisms. RET activation (which may activate MET) involves the tumoral vascular component by means of RET/MET cross-talk and VEGFA (vascular endothelial growth factor A)/GFRα3 (glial cell–derived neurotrophic factor family receptor α3)/artemin–mediated signaling as revealed by VEGF receptor 2/RET coimmunoprecipitation. MET activation involves the cellular tumor component by means of a direct ligand-dependent loop and indirect GFRα3 (RET coreceptor)/artemin–mediated signaling. About downstream signaling, the association of AKT activation with the round cell variant is interesting. No relevant changes in the original RTK activation profiles were observed in the posttreatment cases, a finding that is in keeping with the nontargeted treatments used.Conclusions: These findings highlight the particular cell-specific activation profile of RET/GFRα3 and MET in MLS, and the close correlation between AKT activation and the round cell variant, thus opening up new therapeutic perspectives for MET/AKT inhibitors and antagonistic small molecules binding GFRα3. Clin Cancer Res; 16(14); 3581–93. ©2010 AACR.

Supplementary Figure 1 from Antimitotic effect of the retinoid 4-oxo-fenretinide through inhibition of tubulin polymerization: a novel mechanism of retinoid growth–inhibitory activity

The retinoid 4-oxo-N-(4-hydroxyphenyl)retinamide (4-oxo-4-HPR), a metabolite of fenretinide (4-HPR) present in plasma of 4-HPR–treated patients, is very effective in inducing growth inhibition and apoptosis in several cancer cell lines. 4-Oxo-4-HPR and 4-HPR have different mechanisms of action because 4-oxo-4-HPR, unlike 4-HPR, causes marked cell accumulation in G2-M phase. Here, we investigated the molecular events involving 4-oxo-4-HPR–induced cell cycle perturbation in ovarian (A2780 and IGROV-1) and breast (T47D, estrogen receptor+ and BT-20, estrogen receptor-) cancer cells. 4-Oxo-4-HPR induced a delay of mitosis (with mitotic index increasing 5- to 6-fold in all cell lines) without progression beyond the anaphase, as shown by cyclin B1 expression. 4-Oxo-4-HPR induced multipolar spindle formation and phosphorylation of BUBR1, resulting in activation of the spindle checkpoint. Multipolar spindles were not due to impairment of pole-focusing process, loss of centrosome integrity, or modulation of the expression levels of molecules associated with spindle aberrations (Kif 1C, Kif 2A, Eg5, Tara, tankyrase-1, centractin, and TOGp). We show here that 4-oxo-4-HPR targets microtubules because, in treated cells, it interfered with the reassembly of cold-depolymerized spindle microtubules and decreased the polymerized tubulin fraction. In cell-free assays, 4-oxo-4-HPR inhibited tubulin polymerization (50% inhibition of microtubule assembly at 5.9 μmol/L), suggesting a direct molecular interaction with tubulin. In conclusion, by showing that 4-oxo-4-HPR causes mitotic arrest through antimicrotubule activities, we delineate a new molecular mechanism for a retinoid. [Mol Cancer Ther 2009;8(12):3360–8]

MiR-9 regulates PDGFRbeta expression in TNBC cell lines

Organization of cancer cells into endothelial-like cell-lined structures to support neovascularization and to fuel solid tumors is a hallmark of progression and poor outcome. In triple-negative breast cancer (TNBC), PDGFRβ has been identified as a key player of this process and is considered a promising target for breast cancer therapy. Thus, we aimed at investigating the role of miRNAs as a therapeutic approach to inhibit PDGFRβ-mediated vasculogenic properties of TNBC, focusing on miR-9 and miR-200. In MDA-MB-231 and MDA-MB-157 TNBC cell lines, miR-9 and miR-200 promoted and inhibited, respectively, the formation of vascular-like structures in vitro. Induction of endogenous miR-9 expression, upon ligand-dependent stimulation of PDGFRβ signaling, promoted significant vascular sprouting of TNBC cells, in part, by direct repression of STARD13. Conversely, ectopic expression of miR-200 inhibited this sprouting by indirectly reducing the protein levels of PDGFRβ through the direct suppression of ZEB1. Notably, in vivo miR-9 inhibition or miR-200c restoration, through either the generation of MDA-MB-231–stable clones or peritumoral delivery in MDA-MB-231 xenografted mice, strongly decreased the number of vascular lacunae. Finally, IHC and immunofluorescence analyses in TNBC specimens indicated that PDGFRβ expression marked tumor cells engaged in vascular lacunae. In conclusion, our results demonstrate that miR-9 and miR-200 play opposite roles in the regulation of the vasculogenic ability of TNBC, acting as facilitator and suppressor of PDGFRβ, respectively. Moreover, our data support the possibility to therapeutically exploit miR-9 and miR-200 to inhibit the process of vascular lacunae formation in TNBC. Cancer Res; 76(18); 5562–72. ©2016 AACR.

MiR-200 family inhibits tube formation ability through PDGFRbeta repression

The file contains all the supplementary tables (S1-S4): - Supplementary Table S1. Clinicopathologic features of 78 breast cancer patients (set 1) and 85 TNBC (set 2). - Supplementary Table S2. Relation between miR-9 expression and clinicopathologic characteristics in human breast cancer. - Supplementary Table S3. Top 40 genes predicted as miR-9 target and statistically significant down-modulated in basal versus luminal breast cancer. - Supplementary Table S4. Relation between clinicopathologic characteristics and miR-9 and miR-200c in TNBC human tissues.

Supplementary Figure 5 from microRNA-205 Regulates HER3 in Human Breast Cancer

Supplementary Figure 2 from microRNA-205 Regulates HER3 in Human Breast Cancer

Supplementary Table 5 from MicroRNA Signatures in Human Ovarian Cancer

Supplementary Figure 3 from microRNA-205 Regulates HER3 in Human Breast Cancer

Supplementary Table 3 from MicroRNA Signatures in Human Ovarian Cancer

Supplementary Table 2 from MicroRNA Signatures in Human Ovarian Cancer

Supplementary Table 1 from MicroRNA Signatures in Human Ovarian Cancer

Epithelial ovarian cancer (EOC) is the sixth most common cancer in women worldwide and, despite advances in detection and therapies, it still represents the most lethal gynecologic malignancy in the industrialized countries. Unfortunately, still relatively little is known about the molecular events that lead to the development of this highly aggressive disease. The relatively recent discovery of microRNAs (miRNA), a class of small noncoding RNAs targeting multiple mRNAs and triggering translation repression and/or RNA degradation, has revealed the existence of a new level of gene expression regulation. Multiple studies involving various types of human cancers proved that miRNAs have a causal role in tumorigenesis. Here we show that, in comparison to normal ovary, miRNAs are aberrantly expressed in human ovarian cancer. The overall miRNA expression could clearly separate normal versus cancer tissues. The most significantly overexpressed miRNAs were miR-200a, miR-141, miR-200c, and miR-200b, whereas miR-199a, miR-140, miR-145, and miR-125b1 were among the most down-modulated miRNAs. We could also identify miRNAs whose expression was correlated with specific ovarian cancer biopathologic features, such as histotype, lymphovascular and organ invasion, and involvement of ovarian surface. Moreover, the levels of miR-21, miR-203, and miR-205, up-modulated in ovarian carcinomas compared with normal tissues, were significantly increased after 5-aza-2′-deoxycytidine demethylating treatment of OVCAR3 cells, suggesting that the DNA hypomethylation could be the mechanism responsible for their overexpression. Our results indicate that miRNAs might play a role in the pathogenesis of human EOC and identify altered miRNA gene methylation as a possible epigenetic mechanism involved in their aberrant expression. [Cancer Res 2007;67(18):8699–707]

Supplementary Table 4 from MicroRNA Signatures in Human Ovarian Cancer

Supplementary Figure 2 from MicroRNA Signatures in Human Ovarian Cancer

Supplementary Figure 1 from microRNA-205 Regulates HER3 in Human Breast Cancer

Supplementary Figure 4 from microRNA-205 Regulates HER3 in Human Breast Cancer