35 research outputs found
Clinical Predictors of Mood Disorders and Prevalence of Neuropsychiatric Symptoms in Patients with Systemic Lupus Erythematosus
Background/Objectives: We aimed to determine the prevalence and clinical correlations of mood disorders in a sample of systemic lupus erythematosus (SLE) patients. Hence, we hypothesized that the prevalence of mood disorders would be lower than reported in the literature and that patients would remain clinically stable and show less damage accrual despite low-dose corticosteroid prescription. Methods: In total, 92 SLE outpatients gave informed consent to participate in this cross-sectional study. Psychiatric and autoimmune clinical data were obtained, and a structured psychiatric interview was performed. The main clinical scales for the assessment of clinical symptomatology were included. To examine the potential relationships of presenting a mood disorder in SLE, clinical correlations and multivariate analyses were performed. Results: Mood disorders were the most prevalent disorder reported by SLE patients (16%), followed by adjustment disorders (5%). A significant proportion of patients presented psychosocial disturbances that did not meet the ICD-10 criteria for psychiatric diagnosis. According to the cut-off criterion for the Montgomery–Åsberg Depression Rating Scale (MADRS), up to 27% of the sample met the clinical criteria for depression. The multivariate analysis revealed a relationship between the presence of a mood disorder with total scores of the MADRS and the Young Mania Rating Scale (YMRS). Conclusions: The prevalence of mood disorders in patients with SLE was lower than previously reported. Although self-report clinical scales are useful for assessing clinical symptomatology, they should not be used in place of a comprehensive standardized interview conducted by a trained mental health specialist. Multidisciplinary teamwork is required for the early identification and therapeutic management of autoimmune patients with neuropsychiatric disorders.Funding for this study was supported by the Basque Government via 2016111021 and IT 1512-22 grants
Expression and activity profiles of DPP IV/CD26 and NEP/CD10 glycoproteins in the human renal cancer are tumor-type dependent
[Background]
Cell-surface glycoproteins play critical roles in cell-to-cell recognition, signal transduction and regulation, thus being crucial in cell proliferation and cancer etiogenesis and development. DPP IV and NEP are ubiquitous glycopeptidases closely linked to tumor pathogenesis and development, and they are used as markers in some cancers. In the present study, the activity and protein and mRNA expression of these glycoproteins were analysed in a subset of clear-cell (CCRCC) and chromophobe (ChRCC) renal cell carcinomas, and in renal oncocytomas (RO).[Methods]
Peptidase activities were measured by conventional enzymatic assays with fluorogen-derived substrates. Gene expression was quantitatively determined by qRT-PCR and membrane-bound protein expression and distribution analysis was performed by specific immunostaining.Peer reviewe
Doñana. Acta vertebrata. vol 12(1)
Contribución a la biometría y biología de la Bermejuela Rutilus arcasii (Steindch., 1866) del embalse de PinillaSistemática de iguanidae, sensu lato y de anolinae en Cuba (Repitilia, sauria)Nueva subespecie de Anolis isolepis (Lacertilia: Iguanidae) para CubaAlimentación del ratonero común (Buteo buteo,L. 1758) en el norte de España.Censo y datos sobre la biología del Halcón de Eleonor (Falco eleonorae Gené, 1839) en las Islas Canarias. Agosto-septiembre 1983Selección de hábitat en un grupo de aves forestales del norte de la Península Ibérica:Importancia de la estructura de la vegetación y competencia interespecíficaThe intersexual differentiation in the foraging behaviour of Oenanthe hispanica L. during the breeding seasonEtograma de Gazella dorcasAlgunos datos sobre el crecimiento y las dimorfometrías sexuales del esqueleto postcraneal de Mus spretus Lataste, 1883 (Rodentia: muridaeDistribución y taxonomía de Molossops temminckii (Chiroptera, Molossidae) en Venezuela.Estudio de una población rural de ratones (Mus musculus L.) II. Análisis comparativo de once estimadores del tamaño poblacional.Distribución de Hyla arborea L. (AMPHIBIA, ANURA, HYLIDAE) en el macizo ibérico septentrionaPresencia y nidificación de gavilán (Accipiter nisus granti Sharpe 1890) en la isla de el Hierro.Autumn food of the ptarmigan (Lagopus mutus Montin, 17776 in the spanish central pyreneesPollo atípico en nido de Hirundo rustica.Primera cita del chorlito social (Vanellus gragarius) en las marismas del GuadalquivirPeer reviewe
Bladder cancer index: cross-cultural adaptation into Spanish and psychometric evaluation
BACKGROUND: The Bladder Cancer Index (BCI) is so far the only instrument applicable across all bladder cancer patients, independent of tumor infiltration or treatment applied. We developed a Spanish version of the BCI, and assessed its acceptability and metric properties. METHODS: For the adaptation into Spanish we used the forward and back-translation method, expert panels, and cognitive debriefing patient interviews. For the assessment of metric properties we used data from 197 bladder cancer patients from a multi-center prospective study. The Spanish BCI and the SF-36 Health Survey were self-administered before and 12 months after treatment. Reliability was estimated by Cronbach's alpha. Construct validity was assessed through the multi-trait multi-method matrix. The magnitude of change was quantified by effect sizes to assess responsiveness. RESULTS: Reliability coefficients ranged 0.75-0.97. The validity analysis confirmed moderate associations between the BCI function and bother subscales for urinary (r = 0.61) and bowel (r = 0.53) domains; conceptual independence among all BCI domains (r ≤ 0.3); and low correlation coefficients with the SF-36 scores, ranging 0.14-0.48. Among patients reporting global improvement at follow-up, pre-post treatment changes were statistically significant for the urinary domain and urinary bother subscale, with effect sizes of 0.38 and 0.53. CONCLUSIONS: The Spanish BCI is well accepted, reliable, valid, responsive, and similar in performance compared to the original instrument. These findings support its use, both in Spanish and international studies, as a valuable and comprehensive tool for assessing quality of life across a wide range of bladder cancer patients
Production of a short recombinant C4V3 HIV-1 immunogen that induces strong anti-HIV responses by systemic and mucosal routes without the need of adjuvants
Synthetic peptides have been shown to evoke neutralizing and cytotoxic protective anti-HIV responses in mice and other animal models. Recent data support that C4V3 peptides can induce anti- V3 antibodies that neutralize primary isolates. Critical to the success of peptide-based vaccines is the development of strategies to augment their immunogenicity while reducing their large-scale production costs. Therefore, finding efficient and economical alternatives for the production of epitopic vaccines could have an impact on researches using such immunogens. Herein, we report the recombinant production and immunological characterization of a short polypeptide which carries the three relevant epitopes contained in a C4V3 peptide. This polypeptide, named rC4V3, was efficiently produced in E. coli, yielding more than 75 mg per culture liter. No major difficulties were found in the recovery, refolding and purification of this peptide; the latter facilitated by C-terminal inclusion of a histidine tag. The immunogenicity of this protein was studied by administering it intramuscularly or intranasally to mice and it demonstrated to be a strong elicitor of anti-HIV antibodies at systemic and mucosal compartments. Remarkably, such responses were attained with rC4V3 even without the need of adjuvants. We can conclude that this protein might be a promising tool for studies using epitope-based vaccine designs
Abstract 3246: Pharmacologic targeting of the Hedgehog (HH) signal transduction pathway significantly suppresses growth of malignant pleural mesothelioma (MPM) and non-small cell lung cancer (NSCLC) cells in vitro
Abstract
OBJECTIVE. The HH signal transduction pathway plays crucial roles in organ morphogenesis and is active during embryonic development but quiescent in terminally differentiated cells. Binding of HH ligands to PTCH1 relieves its inhibitory activity on the pathway activator SMO leading to pathway activation and upregulation of target gene expression including the transcription factor Gli1 that serves as marker of pathway activation. It is reactivated in many solid cancers including NSCLC as we have previously demonstrated and proven to be the key oncogenic driver in tumors such as skin basal cell carcinoma. The aim of this study is to determine if HH pathway regulates cell growth and survival of MPM cells and to evaluate the efficacy of pathway blockade using SMO antagonists (SMO inhibitor GDC0449 - GDC or the antifungal drug itraconazole -ITRA) or Gli inhibitors (GANT61 or the anti-leukemia drug arsenic trioxide - ATO) in suppressing the viability of not only NSCLC but also MPM cells.
METHODS. Expression of main components of HH pathway in 8 MPM cells was assessed by qRT-PCR. Suppression of HH/SMO-mediated signaling by these pathway antagonists was determined by LightII cells. Selective knockdown of SMO to inhibit HH signaling was achieved by siRNA in 3 MPM cells H2373, Gardner and H2452. Cell viability following treatments with GDC, ITRA, GANT61or ATO were evaluated in a panel of 8 MPM cells and 8 NSCLC cells using MTT assay. Apoptosis was determined by annexinV/PE staining and flow cytometry.
RESULTS. All MPM cells, similar to previously demonstrated in NSCLC cells, express varying levels of HH ligands, PTCH1, SMO with readily detectable Gli1 observed in 7/8 of MPM cells by qRT-PCR. SMO siRNA mediate 2- to 3-fold reduction of SMO and also of Gli1 gene expression by qRT-PCR, indicating significant HH pathway blockade. This was associated with 40±6% to 70±8% reduction of cell viability (p<0.01 versus non-target siRNA controls). All 4 pathway antagonists completely blocked HH activation in LightII reporter cells. Treating MPM or NSCLC cells with HH inhibitors resulted in 1.5- to 4-fold reduction of Gli1 expression. GANT61, ATO, ITRA and to a lesser degree GDC significantly suppressed viability of all cancer cells at low microM concentrations. More importantly, ITRA, ATO, GANT61 induce significant apoptosis (ranging from 30% to 60%) in representative MPM or NSCLC cells.
CONCLUSIONS. HH signaling is active in MPM and regulates cell viability. ATO and ITRA are as effective as the prototypic SMO inhibitor GDC and the Gli inhibitor GANT61 in suppressing HH signaling in MPM and NSCLC cells. Pharmaceuticals that are FDA-approved for other indications but recently found to have anti-HH activity such as ATO or ITRA may be repurposed to treat HH-dependent MPM or NSCLC cells.
Citation Format: Min You, Javier Varona Santos, David J. Robbins, Niramol Savaraj, Dao M. Nguyen. Pharmacologic targeting of the Hedgehog (HH) signal transduction pathway significantly suppresses growth of malignant pleural mesothelioma (MPM) and non-small cell lung cancer (NSCLC) cells in vitro. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3246. doi:10.1158/1538-7445.AM2013-3246</jats:p
Targeting of the Hedgehog signal transduction pathway suppresses survival of malignant pleural mesothelioma cells in vitro
The present study sought to determine whether the Hedgehog (Hh) pathway is active and regulates the cell growth of cultured malignant pleural mesothelioma (MPM) cells and to evaluate the efficacy of pathway blockade using smoothened (SMO) antagonists (SMO inhibitor GDC-0449 or the antifungal drug itraconazole [ITRA]) or Gli inhibitors (GANT61 or the antileukemia drug arsenic trioxide [ATO]) in suppressing MPM viability.
Selective knockdown of SMO to inhibit Hh signaling was achieved by small interfering RNA in 3 representative MPM cells. The growth inhibitory effect of GDC-0449, ITRA, GANT61, and ATO was evaluated in 8 MPM lines, with cell viability quantified using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell death was determined by annexinV/propidium iodide staining and flow cytometry.
SMO small interfering RNA mediated a two- to more than fivefold reduction of SMO and Gli1 gene expression as determined by real-time quantitative reverse-transcriptase polymerase chain reaction, indicating significant Hh pathway blockade. This was associated with significantly reduced cell viability (34% ± 7% to 61% ± 14% of nontarget small interfering RNA controls; P = .0024 to P = .043). Treating MPM cells with Hh inhibitors resulted in a 1.5- to 4-fold reduction of Gli1 expression. These 4 Hh antagonists strongly suppressed MPM cell viability. More importantly, ITRA, ATO, GANT61 induced significant apoptosis in the representative MPM cells.
Hh signaling is active in MPM and regulates cell viability. ATO and ITRA were as effective as the prototypic SMO inhibitor GDC-0449 and the Gli inhibitor GANT61 in suppressing Hh signaling in MPM cells. Pharmaceutical agents Food and Drug Administration-approved for other indications but recently found to have anti-Hh activity, such as ATO or ITRA, could be repurposed to treat MPM
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Adaptive and maladaptive roles of lipid droplets in health and disease
Advances in the understanding of lipid droplet biology have revealed essential roles for these organelles in mediating proper cellular homeostasis and stress response. Lipid droplets were initially thought to play a passive role in energy storage. However, recent studies demonstrate that they have substantially broader functions, including protection from reactive oxygen species, endoplasmic reticulum stress, and lipotoxicity. Dysregulation of lipid droplet homeostasis is associated with various pathologies spanning neurological, metabolic, cardiovascular, oncological, and renal diseases. This review provides an overview of the current understanding of lipid droplet biology in both health and disease
The combination of ADI-PEG20 and TRAIL effectively increases cell death in melanoma cell lines
Current treatment for advanced, metastatic melanoma is not very effective, and new modalities are needed. ADI-PEG20 is a drug that specifically targets ASS-negative malignant melanomas while sparing the ASS-expressing normal cells. Although laboratory research and clinical trials showed promising results, there are some ASS-negative cell lines and patients that can develop resistance to this drug. In this report, we combined ADI-PEG20 with another antitumor drug TRAIL to increase the killing of malignant melanoma cells. This combination can greatly inhibit cell growth (to over 80%) and also enhanced cell death (to over 60%) in four melanoma cell lines tested compared with control. We found that ADI-PEG20 could increase the cell surface receptors DR4/5 for TRAIL and that caspase activity correlated with the increased cell death. These two drugs could also increase the level of Noxa while decrease that of survivin. We propose that these two drugs can complement each other by activating the intrinsic and extrinsic apoptosis pathways, thus enhance the killing of melanoma cells