24 results on '"Merlos, A."'
Search Results
2. Development of a novel in vitro assay to screen for neuroprotective drugs against iatrogenic neurite shortening.
- Author
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Antón L Martínez, José Brea, Mateo Barro, Xavier Monroy, Manuel Merlos, Javier Burgueño, and María Isabel Loza
- Subjects
Medicine ,Science - Abstract
This work tries to help overcome the lack of relevant translational screening assays, as a limitation for the identification of novel analgesics for neuropathic pain. Hyperexcitability and neurite shortening are common adverse effects of antiviral and antitumor drugs, leading to neuropathic pain. Now, as seen in the drug screening that we developed here, a high-content microscopy-based assay with immortalized dorsal root ganglia (DRG) neurons (differentiated F11 cells) allowed to identify drugs able to protect against the iatrogenic neurite shortening induced by the antitumor drug vincristine and the antiviral drug rilpivirine. We observed that vincristine and rilpivirine induced a significant reduction in the neurite length, which was reverted by α-lipoic acid. We had also evidenced protective effects of pregabalin and melatonin, acting through the α2δ-2 subunit of the voltage-dependent calcium channels and the MT1 receptor, respectively. Additionally, two hits originated from a previous primary screening aimed to detect inhibitors of hyperexcitability to inflammatory mediators in DRG neurons (nitrendipine and felodipine) also prevented neurite shortening in our model. In summary, in this work we developed a novel secondary assay for identifying hits with neuroprotective effect against iatrogenic neurite shortening, consistent with the anti-hyperexcitability action previously tested: highlighting nitrendipine and felodipine against iatrogenic damage in DRG neurons.
- Published
- 2021
- Full Text
- View/download PDF
3. Correction: The Zinc-Schiff Base-Novicidin Complex as a Potential Prostate Cancer Therapy.
- Author
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Vedran Milosavljevic, Yazan Haddad, Miguel Angel Merlos Rodrigo, Amitava Moulick, Hana Polanska, David Hynek, Zbynek Heger, Pavel Kopel, and Vojtech Adam
- Subjects
Medicine ,Science - Abstract
[This corrects the article DOI: 10.1371/journal.pone.0163983.].
- Published
- 2018
- Full Text
- View/download PDF
4. Correction: The Zinc-Schiff Base-Novicidin Complex as a Potential Prostate Cancer Therapy
- Author
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Milosavljevic, Vedran, primary, Haddad, Yazan, additional, Merlos Rodrigo, Miguel Angel, additional, Moulick, Amitava, additional, Polanska, Hana, additional, Hynek, David, additional, Heger, Zbynek, additional, Kopel, Pavel, additional, and Adam, Vojtech, additional
- Published
- 2022
- Full Text
- View/download PDF
5. The Zinc-Schiff Base-Novicidin Complex as a Potential Prostate Cancer Therapy.
- Author
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Vedran Milosavljevic, Yazan Haddad, Miguel Angel Merlos Rodrigo, Amitava Moulick, Hana Polanska, David Hynek, Zbynek Heger, Pavel Kopel, and Vojtech Adam
- Subjects
Medicine ,Science - Abstract
Prostate cancer cells control energy metabolism by chelating intracellular zinc. Thus, zinc delivery has been a popular therapeutic approach for prostate cancer. Here, we propose the use of the membrane-penetrating peptide Novicidin connected to zinc-Schiff base as a carrier vehicle for the delivery of zinc to prostate cells. Mass spectrometry, electrochemistry and spectrophotometry confirmed the formation/stability of this complex and provided insight regarding the availability of zinc for complex interactions. This delivery system showed minor toxicity in normal PNT1A cells and high potency towards PC3 tumor cells. The complex preferentially penetrated PC3 tumor cells in contrast to confinement to the membranes of PNT1A. Furthermore, zinc uptake was confirmed in both cell lines. Molecular analysis was used to confirm the activation of zinc stress (e.g., ZnT-1) and apoptosis (e.g., CASP-1). Our results strongly suggest that the zinc-Schiff base-Novicidin complex has great potential as a novel anticancer drug.
- Published
- 2016
- Full Text
- View/download PDF
6. Sarcosine Up-Regulates Expression of Genes Involved in Cell Cycle Progression of Metastatic Models of Prostate Cancer.
- Author
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Zbynek Heger, Miguel Angel Merlos Rodrigo, Petr Michalek, Hana Polanska, Michal Masarik, Vitezslav Vit, Mariana Plevova, Dalibor Pacik, Tomas Eckschlager, Marie Stiborova, and Vojtech Adam
- Subjects
Medicine ,Science - Abstract
The effects of sarcosine on the processes driving prostate cancer (PCa) development remain still unclear. Herein, we show that a supplementation of metastatic PCa cells (androgen independent PC-3 and androgen dependent LNCaP) with sarcosine stimulates cells proliferation in vitro. Similar stimulatory effects were observed also in PCa murine xenografts, in which sarcosine treatment induced a tumor growth and significantly reduced weight of treated mice (p < 0.05). Determination of sarcosine metabolism-related amino acids and enzymes within tumor mass revealed significantly increased glycine, serine and sarcosine concentrations after treatment accompanied with the increased amount of sarcosine dehydrogenase. In both tumor types, dimethylglycine and glycine-N-methyltransferase were affected slightly, only. To identify the effects of sarcosine treatment on the expression of genes involved in any aspect of cancer development, we further investigated expression profiles of excised tumors using cDNA electrochemical microarray followed by validation using the semi-quantitative PCR. We found 25 differentially expressed genes in PC-3, 32 in LNCaP tumors and 18 overlapping genes. Bioinformatical processing revealed strong sarcosine-related induction of genes involved particularly in a cell cycle progression. Our exploratory study demonstrates that sarcosine stimulates PCa metastatic cells irrespectively of androgen dependence. Overall, the obtained data provides valuable information towards understanding the role of sarcosine in PCa progression and adds another piece of puzzle into a picture of sarcosine oncometabolic potential.
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- 2016
- Full Text
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7. Overlapping DNA methylation dynamics in mouse intestinal cell differentiation and early stages of malignant progression.
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Marta Forn, Anna Díez-Villanueva, Anna Merlos-Suárez, Mar Muñoz, Sergi Lois, Elvira Carriò, Mireia Jordà, Anna Bigas, Eduard Batlle, and Miguel A Peinado
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Medicine ,Science - Abstract
Mouse models of intestinal crypt cell differentiation and tumorigenesis have been used to characterize the molecular mechanisms underlying both processes. DNA methylation is a key epigenetic mark and plays an important role in cell identity and differentiation programs and cancer. To get insights into the dynamics of cell differentiation and malignant transformation we have compared the DNA methylation profiles along the mouse small intestine crypt and early stages of tumorigenesis. Genome-scale analysis of DNA methylation together with microarray gene expression have been applied to compare intestinal crypt stem cells (EphB2high), differentiated cells (EphB2negative), ApcMin/+ adenomas and the corresponding non-tumor adjacent tissue, together with small and large intestine samples and the colon cancer cell line CT26. Compared with late stages, small intestine crypt differentiation and early stages of tumorigenesis display few and relatively small changes in DNA methylation. Hypermethylated loci are largely shared by the two processes and affect the proximities of promoter and enhancer regions, with enrichment in genes associated with the intestinal stem cell signature and the PRC2 complex. The hypermethylation is progressive, with minute levels in differentiated cells, as compared with intestinal stem cells, and reaching full methylation in advanced stages. Hypomethylation shows different signatures in differentiation and cancer and is already present in the non-tumor tissue adjacent to the adenomas in ApcMin/+ mice, but at lower levels than advanced cancers. This study provides a reference framework to decipher the mechanisms driving mouse intestinal tumorigenesis and also the human counterpart.
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- 2015
- Full Text
- View/download PDF
8. Correction: The Zinc-Schiff Base-Novicidin Complex as a Potential Prostate Cancer Therapy
- Author
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Pavel Kopel, Vojtech Adam, Vedran Milosavljevic, Yazan Haddad, Hana Polanska, Zbynek Heger, Miguel Angel Merlos Rodrigo, David Hynek, and Amitava Moulick
- Subjects
Fluorescence-lifetime imaging microscopy ,Urology ,Cancer Treatment ,lcsh:Medicine ,Gene Expression ,chemistry.chemical_element ,Apoptosis ,Zinc ,Biochemistry ,chemistry.chemical_compound ,Prostate cancer ,Exocrine Glands ,Genetics ,Medicine and Health Sciences ,Fluorescence microscope ,medicine ,Gene Regulation ,Centrifugation ,lcsh:Science ,Schiff base ,Multidisciplinary ,Cell Death ,Prostate Cancer ,lcsh:R ,Prostate Diseases ,Biology and Life Sciences ,Cancers and Neoplasms ,Biological Transport ,Cell Biology ,medicine.disease ,Chemistry ,Genitourinary Tract Tumors ,Metabolism ,Oncology ,chemistry ,Cell Processes ,Physical Sciences ,lcsh:Q ,Prostate Gland ,Anatomy ,Zinc Transporters ,Research Article ,Chemical Elements - Abstract
Prostate cancer cells control energy metabolism by chelating intracellular zinc. Thus, zinc delivery has been a popular therapeutic approach for prostate cancer. Here, we propose the use of the membrane-penetrating peptide Novicidin connected to zinc-Schiff base as a carrier vehicle for the delivery of zinc to prostate cells. Mass spectrometry, electrochemistry and spectrophotometry confirmed the formation/stability of this complex and provided insight regarding the availability of zinc for complex interactions. This delivery system showed minor toxicity in normal PNT1A cells and high potency towards PC3 tumor cells. The complex preferentially penetrated PC3 tumor cells in contrast to confinement to the membranes of PNT1A. Furthermore, zinc uptake was confirmed in both cell lines. Molecular analysis was used to confirm the activation of zinc stress (e.g., ZnT-1) and apoptosis (e.g., CASP-1). Our results strongly suggest that the zinc-Schiff base-Novicidin complex has great potential as a novel anticancer drug.
- Published
- 2022
9. Conserved mechanisms of tumorigenesis in the Drosophila adult midgut.
- Author
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Òscar Martorell, Anna Merlos-Suárez, Kyra Campbell, Francisco M Barriga, Christo P Christov, Irene Miguel-Aliaga, Eduard Batlle, Jordi Casanova, and Andreu Casali
- Subjects
Medicine ,Science - Abstract
Whereas the series of genetic events leading to colorectal cancer (CRC) have been well established, the precise functions that these alterations play in tumor progression and how they disrupt intestinal homeostasis remain poorly characterized. Activation of the Wnt/Wg signaling pathway by a mutation in the gene APC is the most common trigger for CRC, inducing benign lesions that progress to carcinomas due to the accumulation of other genetic alterations. Among those, Ras mutations drive tumour progression in CRC, as well as in most epithelial cancers. As mammalian and Drosophila's intestines share many similarities, we decided to explore the alterations induced in the Drosophila midgut by the combined activation of the Wnt signaling pathway with gain of function of Ras signaling in the intestinal stem cells. Here we show that compound Apc-Ras clones, but not clones bearing the individual mutations, expand as aggressive intestinal tumor-like outgrowths. These lesions reproduce many of the human CRC hallmarks such as increased proliferation, blockade of cell differentiation and cell polarity and disrupted organ architecture. This process is followed by expression of tumoral markers present in human lesions. Finally, a metabolic behavioral assay shows that these flies suffer a progressive deterioration in intestinal homeostasis, providing a simple readout that could be used in screens for tumor modifiers or therapeutic compounds. Taken together, our results illustrate the conservation of the mechanisms of CRC tumorigenesis in Drosophila, providing an excellent model system to unravel the events that, upon mutation in Apc and Ras, lead to CRC initiation and progression.
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- 2014
- Full Text
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10. Development of a novel in vitro assay to screen for neuroprotective drugs against iatrogenic neurite shortening
- Author
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Javier Burgueño, Manuel Merlos, María Isabel Loza, Antón L. Martínez, Mateo Barro, Xavier Monroy, and José Brea
- Subjects
Iatrogenic Disease ,Pregabalin ,Drug Evaluation, Preclinical ,Pharmacology ,Biochemistry ,Nitrendipine ,Animal Cells ,Ganglia, Spinal ,Medicine and Health Sciences ,Melatonin ,Neurons ,Analgesics ,Multidisciplinary ,Voltage-dependent calcium channel ,Thioctic Acid ,Antimicrobials ,Pharmaceutics ,Drugs ,Cell Differentiation ,Antivirals ,Neuroprotective Agents ,Vincristine ,Neuropathic pain ,Medicine ,Cellular Types ,medicine.drug ,Research Article ,Neurite ,medicine.drug_class ,Science ,Pain ,Neuroprotection ,Microbiology ,Cell Line ,Signs and Symptoms ,Drug Therapy ,Microbial Control ,Virology ,medicine ,Neurites ,Humans ,Neuropathic Pain ,business.industry ,Rilpivirine ,Biology and Life Sciences ,Cell Biology ,Neuronal Dendrites ,Hormones ,Felodipine ,Cellular Neuroscience ,Neuralgia ,Antiviral drug ,Clinical Medicine ,business ,Neuroprotectives ,Neuroscience ,Developmental Biology - Abstract
This work tries to help overcome the lack of relevant translational screening assays, as a limitation for the identification of novel analgesics for neuropathic pain. Hyperexcitability and neurite shortening are common adverse effects of antiviral and antitumor drugs, leading to neuropathic pain. Now, as seen in the drug screening that we developed here, a high-content microscopy-based assay with immortalized dorsal root ganglia (DRG) neurons (differentiated F11 cells) allowed to identify drugs able to protect against the iatrogenic neurite shortening induced by the antitumor drug vincristine and the antiviral drug rilpivirine. We observed that vincristine and rilpivirine induced a significant reduction in the neurite length, which was reverted by α-lipoic acid. We had also evidenced protective effects of pregabalin and melatonin, acting through the α2δ-2 subunit of the voltage-dependent calcium channels and the MT1receptor, respectively. Additionally, two hits originated from a previous primary screening aimed to detect inhibitors of hyperexcitability to inflammatory mediators in DRG neurons (nitrendipine and felodipine) also prevented neurite shortening in our model. In summary, in this work we developed a novel secondary assay for identifying hits with neuroprotective effect against iatrogenic neurite shortening, consistent with the anti-hyperexcitability action previously tested: highlighting nitrendipine and felodipine against iatrogenic damage in DRG neurons.
- Published
- 2021
11. Development of a novel in vitro assay to screen for neuroprotective drugs against iatrogenic neurite shortening
- Author
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Martínez, Antón L., primary, Brea, José, additional, Barro, Mateo, additional, Monroy, Xavier, additional, Merlos, Manuel, additional, Burgueño, Javier, additional, and Loza, María Isabel, additional
- Published
- 2021
- Full Text
- View/download PDF
12. Metabolic alterations and increased liver mTOR expression precede the development of autoimmune disease in a murine model of lupus erythematosus.
- Author
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Laia Vilà, Núria Roglans, Miguel Baena, Emma Barroso, Marta Alegret, Manuel Merlos, and Juan C Laguna
- Subjects
Medicine ,Science - Abstract
Although metabolic syndrome (MS) and systemic lupus erythematosus (SLE) are often associated, a common link has not been identified. Using the BWF1 mouse, which develops MS and SLE, we sought a molecular connection to explain the prevalence of these two diseases in the same individuals. We determined SLE- markers (plasma anti-ds-DNA antibodies, splenic regulatory T cells (Tregs) and cytokines, proteinuria and renal histology) and MS-markers (plasma glucose, non-esterified fatty acids, triglycerides, insulin and leptin, liver triglycerides, visceral adipose tissue, liver and adipose tissue expression of 86 insulin signaling-related genes) in 8-, 16-, 24-, and 36-week old BWF1 and control New-Zealand-White female mice. Up to week 16, BWF1 mice showed MS-markers (hyperleptinemia, hyperinsulinemia, fatty liver and visceral adipose tissue) that disappeared at week 36, when plasma anti-dsDNA antibodies, lupus nephritis and a pro-autoimmune cytokine profile were detected. BWF1 mice had hyperleptinemia and high splenic Tregs till week 16, thereby pointing to leptin resistance, as confirmed by the lack of increased liver P-Tyr-STAT-3. Hyperinsulinemia was associated with a down-regulation of insulin related-genes only in adipose tissue, whereas expression of liver mammalian target of rapamicyn (mTOR) was increased. Although leptin resistance presented early in BWF1 mice can slow-down the progression of autoimmunity, our results suggest that sustained insulin stimulation of organs, such as liver and probably kidneys, facilitates the over-expression and activity of mTOR and the development of SLE.
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- 2012
- Full Text
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13. Choice of the initial antiretroviral treatment for HIV-positive individuals in the era of integrase inhibitors
- Author
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Alejos, Belen, Suarez-Garcia, Ines, Bisbal, Otilia, Antonio Iribarren, Jose, Asensi, Victor, Gorgolas, Miguel, Muga, Roberto, Moreno, Santiago, Jarrin, Inma, Dalmau, David, Luisa Navarro, Maria, Isabel Gonzalez, Maria, Luis Blanco, Jose, Garcia, Federico, Rubio, Rafael, Gutierrez, Felix, Vidal, Francesc, Berenguer, Juan, Gonzalez, Juan, Hernando, Victoria, Moreno, Cristina, Iniesta, Carlos, Garcia Sousa, Luis Miguel, Sanz Perez, Nieves, Angeles Munoz-Fernandez, M., Maria Garcia-Merino, Isabel, Consuegra Fernandez, Irene, Gomez Rico, Coral, Gallego De la Fuente, Jorge, Palau Concejo, Paula, Portilla, Joaquin, Merino, Esperanza, Reus, Sergio, Boix, Vicente, Giner, Livia, Gadea, Carmen, Portilla, Irene, Pampliega, Maria, Diez, Marcos, Carlos Rodriguez, Juan, Sanchez-Paya, Jose, Luis Gomez, Juan, Hernandez, Jehovana, Remedios Aleman, Maria, del Mar Alonso, Maria, Inmaculada Hernandez, Maria, Diaz-Flores, Felicitas, Garcia, Dacil, Pelazas, Ricardo, Lopez Lirola, Ana, Sanz Moreno, Jose, Arranz Caso, Alberto, Hernandez Gutierrez, Cristina, Novella Mena, Maria, Pulido, Federico, Hernando, Asuncion, Dominguez, Lourdes, Rial Crestelo, David, Bermejo, Laura, Santacreu, Mireia, Arrizabalaga, Julio, Jose Aramburu, Maria, Camino, Xabier, Rodriguez-Arrondo, Francisco, Angel von Wichmann, Miguel, Pascual Tome, Lidia, Angel Goenaga, Miguel, Jesus Bustin-Duy, Ma, Azkune, Harkaitz, Ibarguren, Maialen, Lizardi, Aitziber, Kortajarena, Xabier, Masia, Mar, Padilla, Sergio, Navarro, Andres, Montolio, Fernando, Robledano, Catalina, Gregori Colome, Joan, Adsuar, Araceli, Pascual, Rafael, Fernandez, Marta, Garcia, Elena, Alberto Garcia, Jose, Barber, Xavier, Sanvisens, Arantza, Fuster, Daniel, Lopez Bernaldo de Quiros, Juan Carlos, Gutierrez, Isabel, Ramirez, Margarita, Padilla, Belen, Gijon, Paloma, Aldamiz-Echevarria, Teresa, Tejerina, Francisco, Jose Parras, Francisco, Balsalobre, Pascual, Diez, Cristina, Perez Latorre, Leire, Peraire, Joaquin, Vilades, Consuelo, Veloso, Sergio, Vargas, Montserrat, Lopez-Dupla, Miguel, Olona, Montserrat, Rull, Anna, Rodriguez-Gallego, Esther, Alba, Veronica, Montero Alonso, Marta, Lopez Aldeguer, Jose, Blanes Julia, Marino, Tasias Pitarch, Maria, Castro Hernandez, Ivan, Calabuig Munoz, Eva, Cuellar Tovar, Sandra, Salavert Lleti, Miguel, Fernandez Navarro, Juan, Gonzalez-garcia, Juan, Arnalich, Francisco, Ramon Arribas, Jose, Bernardino de la Serna, Jose Ignacio, Miguel Castro, Juan, Escosa, Luis, Herranz, Pedro, Hontanon, Victor, Garcia-Bujalance, Silvia, Garcia Lopez-Hortelano, Milagros, Gonzalez-Baeza, Alicia, Luz Martin-Carbonero, Maria, Mayoral, Mario, Jose Mellado, Maria, Esteban Mican, Rafael, Montejano, Rocio, Luisa Montes, Maria, Moreno, Victoria, Perez-Valero, Ignacio, Rodes, Berta, Sainz, Talia, Sendagorta, Elena, Stella Alcariz, Natalia, Valencia, Eulalia, Ramon Blanco, Jose, Antonio Oteo, Jose, Ibarra, Valvanera, Metola, Luis, Sanz, Mercedes, Perez-Martinez, Laura, Arazo, Piedad, Samperiz, Gloria, Jaen, Angels, Sanmarti, Montse, Cairo, Mireia, Martinez-Lacasa, Javier, Velli, Pablo, Font, Roser, Xercavins, Mariona, Alonso, Noemi, Rivero, Maria, Reparaz, Jesus, Gracia Ruiz de Alda, Maria, de Leon Cano, Maria Teresa, Pierola Ruiz de Galarreta, Beatriz, Segura, Ferran, Jose Amengual, Maria, Navarro, Gemma, Sala, Montserrat, Cervantes, Manuel, Pineda, Valentin, Calzado, Sonia, Navarro, Marta, de los Santos, Ignacio, Sanz Sanz, Jesus, Salas Aparicio, Ana, Sarria Cepeda, Cristina, Garcia-Fraile Fraile, Lucio, Martin Gayo, Enrique, Luis Casado, Jose, Dronda, Fernando, Moreno, Ana, Perez Elias, Maria Jesus, Gomez Ayerbe, Cristina, Gutierrez, Carolina, Madrid, Nadia, del Campo Terron, Santos, Marti, Paloma, Ansa, Uxua, Serrano, Sergio, Jesus Vivancos, Maria, Bernal, Enrique, Cano, Alfredo, Alcaraz Garcia, Antonia, Bravo Urbieta, Joaquin, Munoz, Angeles, Jose Alcaraz, Maria, del Carmen Villalba, Maria, Hernandez, Jose, Pena, Alejandro, Munoz, Leopoldo, Casas, Paz, Alvarez, Marta, Chueca, Natalia, Vinuesa, David, Martinez-Montes, Clara, Del Romero, Jorge, Rodriguez, Carmen, Puerta, Teresa, Carlos Carrio, Juan, Vera, Mar, Ballesteros, Juan, Ayerdi, Oskar, Antela, Antonio, Losada, Elena, Riera, Melchor, Penaranda, Maria, Leyes, Maria, Angels Ribas, Ma, Campins, Antoni A., Vidal, Carmen, Fanjul, Francisco, Murillas, Javier, Homar, Francisco, Santos, Jesus, Gomez Ayerbe, Crisitina, Viciana, Isabel, Palacios, Rosario, Maria Gonzalez, Carmen, Viciana, Pompeyo, Espinosa, Nuria, Fernando Lopez-Cortes, Luis, Podzamczer, Daniel, Ferrer, Elena, Imaz, Arkaitz, Tiraboschi, Juan, Silva, Ana, Saumoy, Maria, Ribera, Esteban, Curran, Adrian, Olalla, Julian, del Arco, Alfonso, de la Torre, Javier, Luis Prada, Jose, de Lomas Guerrero, Jose Maria Garcia, Perez Stachowski, Javier, Juan Martinez, Onofre, Jesus Vera, Francisco, Martinez, Lorena, Garcia, Josefina, Alcaraz, Begona, Jimeno, Amaya, Castro Iglesias, Angeles, Pernas Souto, Berta, Mena de Cea, Alvaro, Munoz, Josefa, Zurine Zubero, Miren, Mirena Baraia-Etxaburu, Josu, Ibarra Ugarte, Sofia, Ferrero Beneitez, Oscar Luis, Lopez de Munain, Josefina, Camara Lopez, Ma Mar, de la Pena, Mireia, Lopez, Miriam, Galera, Carlos, Albendin, Helena, Perez, Aurora, Iborra, Asuncion, Moreno, Antonio, Angustias Merlos, Maria, Vidal, Asuncion, Amador, Concha, Pasquau, Francisco, Ena, Javier, Benito, Concha, Fenoll, Vicenta, Gil Anguita, Concepcion, Algado Rabasa, Jose Tomas, Malmierca, Eduardo, Gonzalez-Ruano, Patricia, Martin Rodrigo, Dolores, Ruiz Seco, Ma Pilar, Omar Mohamed-Balghata, Mohamed, Gomez Vidal, Maria Amparo, Alberto de Zarraga, Miguel, Estrada Perez, Vicente, Tellez Molina, Maria Jesus, Vergas Garcia, Jorge, Perez-Somarriba Moreno, Juncal, Cabello, Alfonso, Alvarez, Beatriz, Prieto, Laura, Galindo Puerto, Maria Jose, Fernando Vilalta, Ramon, Ferrer Ribera, Ana, Rivero Roman, Antonio, Brieva Herrero, Maria Teresa, Rivero Juarez, Antonio, Lopez Lopez, Pedro, Machuca Sanchez, Isabel, Pena Martinez, Jose, Cervero Jimenez, Miguel, Torres Perea, Rafael, Jusdado Ruiz-Capillas, Juan Jose, Pineda, Juan A., CoRIS Cohort, Instituto de Salud Carlos III, Red Española de Investigación en SIDA, European Commission, ViiV Healthcare, Red de Investigación Cooperativa en Investigación en Sida (España), and Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
- Subjects
Male ,European People ,Spanish People ,Health Care Providers ,Pathology and Laboratory Medicine ,seropositividad al VIH ,Geographical locations ,0302 clinical medicine ,Immunodeficiency Viruses ,Abacavir ,HIV Seropositivity ,Odds Ratio ,Ethnicities ,Public and Occupational Health ,mediana edad ,Antiretrovirals ,adulto ,cociente de probabilidades relativas ,antirretrovirales ,Anti-Retroviral Agents ,Medical Microbiology ,Viral Pathogens ,Medicine ,medicine.medical_specialty ,Sida ,Science ,Immunology ,030106 microbiology ,Investigación médica ,Men WHO Have Sex with Men ,Integrase Inhibitors ,Microbiology ,Tenofovir alafenamide ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,Physicians ,Humans ,Microbial Pathogens ,Pharmacology ,Organisms ,Biology and Life Sciences ,Raltegravir ,Health Care ,Regimen ,chemistry ,Population Groupings ,Preventive Medicine ,Sexuality Groupings ,RNA viruses ,0301 basic medicine ,Medical Doctors ,humanos ,Tratamiento médico ,chemistry.chemical_compound ,Antiretroviral Therapy, Highly Active ,Medicine and Health Sciences ,Medical Personnel ,030212 general & internal medicine ,Hispanic People ,Multidisciplinary ,Antimicrobials ,Cobicistat ,Drugs ,Viral Load ,Middle Aged ,Antivirals ,Vaccination and Immunization ,Europe ,Professions ,Rilpivirine ,Viruses ,Female ,Pathogens ,inhibidores de la integrasa ,Research Article ,medicine.drug ,Adult ,Antiretroviral Therapy ,Emtricitabine ,Antiviral Therapy ,Microbial Control ,Virology ,Internal medicine ,Retroviruses ,medicine ,European Union ,análisis multifactorial ,business.industry ,Lentivirus ,HIV ,Spain ,People and Places ,Multivariate Analysis ,Ritonavir ,business ,Viral Transmission and Infection - Abstract
CoRIS cohort., [Background] We aimed to describe the most frequently prescribed initial antiretroviral therapy (ART) regimens in recent years in HIV-positive persons in the Cohort of the Spanish HIV/AIDS Research Network (CoRIS) and to investigate factors associated with the choice of each regimen., [Methods] We analyzed initial ART regimens prescribed in adults participating in CoRIS from 2014 to 2017. Only regimens prescribed in >5% of patients were considered. We used multivariable multinomial regression to estimate Relative Risk Ratios (RRRs) for the association between sociodemographic and clinical characteristics and the choice of the initial regimen., [Results] Among 2874 participants, abacavir(ABC)/lamivudine(3TC)/dolutegavir(DTG) was the most frequently prescribed regimen (32.1%), followed by tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC)/elvitegravir(EVG)/cobicistat(COBI) (14.9%), TDF/FTC/rilpivirine (RPV) (14.0%), tenofovir alafenamide (TAF)/FTC/EVG/COBI (13.7%), TDF/FTC+DTG (10.0%), TDF/FTC+darunavir/ritonavir or darunavir/cobicistat (bDRV) (9.8%) and TDF/FTC+raltegravir (RAL) (5.6%). Compared with ABC/3TC/DTG, starting TDF/FTC/RPV was less likely in patients with CD4100.000 copies/mL. TDF/FTC+DTG was more frequent in those with CD4100.000 copies/mL. TDF/FTC+RAL and TDF/FTC+bDRV were also more frequent among patients with CD4, [Conclusions] The choice of initial ART regimens is consistent with Spanish guidelines’ recommendations, but is also clearly influenced by physician’s perception based on patient’s clinical and sociodemographic variables and by the prescribing hospital location., The RIS cohort (CoRIS) is supported by the Instituto de Salud Carlos III through the Red Temática de Investigación Cooperativa en Sida (RD06/006, RD12/0017/0018 and RD16/0002/0006) as part of the Plan Nacional I+D+i and cofinanced by ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER). This study was funded by ViiV Healthcare.
- Published
- 2019
14. Correction: The Zinc-Schiff Base-Novicidin Complex as a Potential Prostate Cancer Therapy
- Author
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Milosavljevic, Vedran, primary, Haddad, Yazan, additional, Merlos Rodrigo, Miguel Angel, additional, Moulick, Amitava, additional, Polanska, Hana, additional, Hynek, David, additional, Heger, Zbynek, additional, Kopel, Pavel, additional, and Adam, Vojtech, additional
- Published
- 2018
- Full Text
- View/download PDF
15. The Zinc-Schiff Base-Novicidin Complex as a Potential Prostate Cancer Therapy
- Author
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David Hynek, Pavel Kopel, Yazan Haddad, Hana Polanska, Vedran Milosavljevic, Zbynek Heger, Vojtech Adam, Miguel Angel Merlos Rodrigo, and Amitava Moulick
- Subjects
0301 basic medicine ,Male ,Molecular Conformation ,chemistry.chemical_element ,lcsh:Medicine ,Gene Expression ,Peptide ,Antineoplastic Agents ,Apoptosis ,Zinc ,Biology ,Zinc-Schiff Base-Novicidin Complex ,03 medical and health sciences ,Prostate cancer ,Coordination Complexes ,Cell Line, Tumor ,rakovina prostaty ,medicine ,Humans ,Chelation ,lcsh:Science ,Cation Transport Proteins ,Schiff Bases ,chemistry.chemical_classification ,Sp1 transcription factor ,Multidisciplinary ,Prostate Cancer ,lcsh:R ,Caspase 1 ,Prostatic Neoplasms ,medicine.disease ,3. Good health ,030104 developmental biology ,chemistry ,Biochemistry ,Microscopy, Fluorescence ,Cell culture ,Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ,Komplex Zinek-Schiffova báze-Novicidin ,Toxicity ,lcsh:Q ,Antimicrobial Cationic Peptides - Abstract
Prostate cancer cells control energy metabolism by chelating intracellular zinc. Thus, zinc delivery has been a popular therapeutic approach for prostate cancer. Here, we propose the use of the membrane-penetrating peptide Novicidin connected to zinc-Schiff base as a carrier vehicle for the delivery of zinc to prostate cells. Mass spectrometry, electrochemistry and spectrophotometry confirmed the formation/stability of this complex and provided insight regarding the availability of zinc for complex interactions. This delivery system showed minor toxicity in normal PNT1A cells and high potency towards PC3 tumor cells. The complex preferentially penetrated PC3 tumor cells in contrast to confinement to the membranes of PNT1A. Furthermore, zinc uptake was confirmed in both cell lines. Molecular analysis was used to confirm the activation of zinc stress (e.g., ZnT-1) and apoptosis (e.g., CASP-1). Our results strongly suggest that the zinc-Schiff base-Novicidin complex has great potential as a novel anticancer drug. Buňky rakoviny prostaty ovládají energetický metabolismus chelatací intracelulárního zinku. Tedy dodání zinku bylo populární jako terapeutický přístup k léčbě rakoviny prostaty. Zde navrhujeme použití membránou pronikajícího peptidu novicidinu připojeného k Schiffově bázi se zinkem jako nosného prostředku pro dodání zinku do buněk prostaty. Hmotnostní spektrometrie, elektrochemie a spektrofotometrie potvrdily tvorbu a stabilitu tohoto komplexu a poskytly pochopení ohledně dostupnosti zinku pro komplexní interakce. Tento systém ukázal menší toxicitu v normálních buňkách PNT1A a vysokou účinnost vůči nádorovým buňkám PC3. Komplex přednostně pronikl nádorovými buňkami PC3 na rozdíl od uzavření se membránám PNT1A. Dále byl potvrzen příjem zinku v obou buněčných linií. Molekulární analýza byla použita k potvrzení aktivace zinkového stresu (např. ZnT-1) a apoptózy (např. CASP-1). Naše výsledky silně naznačují, že komplex zinek-Schiffova báze-novicidin má velký potenciál jako nové protinádorové léčivo.
- Published
- 2016
16. Sarcosine Up-Regulates Expression of Genes Involved in Cell Cycle Progression of Metastatic Models of Prostate Cancer
- Author
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Mariana Plevová, Miguel Angel Merlos Rodrigo, Hana Polanska, Tomas Eckschlager, Marie Stiborová, Zbynek Heger, Dalibor Pacík, Petr Michalek, Vitezslav Vit, Vojtech Adam, and Michal Masarik
- Subjects
0301 basic medicine ,Male ,Microarrays ,Cancer Treatment ,lcsh:Medicine ,Gene Expression ,receptors ,Apoptosis ,Glycine N-Methyltransferase ,Biochemistry ,Polymerase Chain Reaction ,Transcriptome ,Serine ,Prostate cancer ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Medicine and Health Sciences ,Cell Cycle and Cell Division ,metabolism-related proteins ,lcsh:Science ,Mice, Inbred BALB C ,Multidisciplinary ,Cell Death ,phosphorylation ,Prostate Cancer ,Cell Cycle ,Prostate Diseases ,Cell cycle ,Glycine N-methyltransferase ,3. Good health ,Up-Regulation ,Gene Expression Regulation, Neoplastic ,Bioassays and Physiological Analysis ,Oncology ,Cell Processes ,030220 oncology & carcinogenesis ,Androgens ,Anatomy ,Research Article ,Sarcosine ,Urology ,proliferation ,Sarcosine Dehydrogenase ,Mice, Nude ,thymidylate synthase ,Biology ,Research and Analysis Methods ,serine ,03 medical and health sciences ,Exocrine Glands ,Cell Line, Tumor ,LNCaP ,medicine ,Genetics ,Animals ,Humans ,breast-cancer ,therapy ,lcsh:R ,Biology and Life Sciences ,Cancers and Neoplasms ,Prostatic Neoplasms ,Cell Biology ,medicine.disease ,one-carbon metabolism ,Molecular biology ,Hormones ,Genitourinary Tract Tumors ,030104 developmental biology ,chemistry ,Sarcosine dehydrogenase ,lcsh:Q ,Prostate Gland ,Neoplasm Transplantation ,glycine ,Genes, Neoplasm - Abstract
The effects of sarcosine on the processes driving prostate cancer (PCa) development remain still unclear. Herein, we show that a supplementation of metastatic PCa cells (androgen independent PC-3 and androgen dependent LNCaP) with sarcosine stimulates cells proliferation in vitro. Similar stimulatory effects were observed also in PCa murine xenografts, in which sarcosine treatment induced a tumor growth and significantly reduced weight of treated mice (p < 0.05). Determination of sarcosine metabolism-related amino acids and enzymes within tumor mass revealed significantly increased glycine, serine and sarcosine concentrations after treatment accompanied with the increased amount of sarcosine dehydrogenase. In both tumor types, dimethylglycine and glycine-N-methyltransferase were affected slightly, only. To identify the effects of sarcosine treatment on the expression of genes involved in any aspect of cancer development, we further investigated expression profiles of excised tumors using cDNA electrochemical microarray followed by validation using the semi-quantitative PCR. We found 25 differentially expressed genes in PC-3, 32 in LNCaP tumors and 18 overlapping genes. Bioinformatical processing revealed strong sarcosine-related induction of genes involved particularly in a cell cycle progression. Our exploratory study demonstrates that sarcosine stimulates PCa metastatic cells irrespectively of androgen dependence. Overall, the obtained data provides valuable information towards understanding the role of sarcosine in PCa progression and adds another piece of puzzle into a picture of sarcosine oncometabolic potential.
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- 2016
17. Sarcosine Up-Regulates Expression of Genes Involved in Cell Cycle Progression of Metastatic Models of Prostate Cancer
- Author
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Heger, Zbynek, primary, Merlos Rodrigo, Miguel Angel, additional, Michalek, Petr, additional, Polanska, Hana, additional, Masarik, Michal, additional, Vit, Vitezslav, additional, Plevova, Mariana, additional, Pacik, Dalibor, additional, Eckschlager, Tomas, additional, Stiborova, Marie, additional, and Adam, Vojtech, additional
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- 2016
- Full Text
- View/download PDF
18. Conserved Mechanisms of Tumorigenesis in the Drosophila Adult Midgut
- Author
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Christo P. Christov, Kyra Campbell, Irene Miguel-Aliaga, Anna Merlos-Suárez, Jordi Casanova, Eduard Batlle, Francisco M. Barriga, Andreu Casali, Òscar Martorell, and Ministerio de Ciencia e Innovación (España)
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Aging ,Anatomy and Physiology ,Carcinogenesis ,Cellular differentiation ,Digestive Physiology ,lcsh:Medicine ,PROGRESSION ,Apoptosis ,medicine.disease_cause ,BETA-CATENIN ,Molecular Cell Biology ,Drosophila Proteins ,lcsh:Science ,Genetics ,Mutation ,Multidisciplinary ,biology ,Stem Cells ,Drosophila Melanogaster ,COLON-CANCER ,PROLIFERATION ,Wnt signaling pathway ,JAK-STAT signaling pathway ,Animal Models ,Multidisciplinary Sciences ,Adult Stem Cells ,DIFFERENTIATION ,Science & Technology - Other Topics ,Cellular Types ,Drosophila Protein ,Research Article ,Signal Transduction ,Beta-catenin ,General Science & Technology ,EPITHELIUM ,Signaling Pathways ,Model Organisms ,MD Multidisciplinary ,Cancer Genetics ,medicine ,Animals ,Biology ,Science & Technology ,lcsh:R ,CONTROLS SELF-RENEWAL ,Epithelial Cells ,Oncogenes ,INTESTINAL-STEM-CELLS ,JAK/STAT ,APC ,Clone Cells ,Gastrointestinal Tract ,Tumor progression ,Genetics of Disease ,ras Proteins ,biology.protein ,Cancer research ,lcsh:Q ,Digestive System ,Developmental Biology - Abstract
Whereas the series of genetic events leading to colorectal cancer (CRC) have been well established, the precise functions that these alterations play in tumor progression and how they disrupt intestinal homeostasis remain poorly characterized. Activation of the Wnt/Wg signaling pathway by a mutation in the gene APC is the most common trigger for CRC, inducing benign lesions that progress to carcinomas due to the accumulation of other genetic alterations. Among those, Ras mutations drive tumour progression in CRC, as well as in most epithelial cancers. As mammalian and Drosophila's intestines share many similarities, we decided to explore the alterations induced in the Drosophila midgut by the combined activation of the Wnt signaling pathway with gain of function of Ras signaling in the intestinal stem cells. Here we show that compound Apc-Ras clones, but not clones bearing the individual mutations, expand as aggressive intestinal tumor-like outgrowths. These lesions reproduce many of the human CRC hallmarks such as increased proliferation, blockade of cell differentiation and cell polarity and disrupted organ architecture. This process is followed by expression of tumoral markers present in human lesions. Finally, a metabolic behavioral assay shows that these flies suffer a progressive deterioration in intestinal homeostasis, providing a simple readout that could be used in screens for tumor modifiers or therapeutic compounds. Taken together, our results illustrate the conservation of the mechanisms of CRC tumorigenesis in Drosophila, providing an excellent model system to unravel the events that, upon mutation in Apc and Ras, lead to CRC initiation and progression. © 2014 Martorell et al., This work was supported by the MICINN (BFU2010-16016 and BFU2011-23479) to A.C.
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- 2014
- Full Text
- View/download PDF
19. The Zinc-Schiff Base-Novicidin Complex as a Potential Prostate Cancer Therapy
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Milosavljevic, Vedran, primary, Haddad, Yazan, additional, Merlos Rodrigo, Miguel Angel, additional, Moulick, Amitava, additional, Polanska, Hana, additional, Hynek, David, additional, Heger, Zbynek, additional, Kopel, Pavel, additional, and Adam, Vojtech, additional
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- 2016
- Full Text
- View/download PDF
20. Overlapping DNA Methylation Dynamics in Mouse Intestinal Cell Differentiation and Early Stages of Malignant Progression
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Forn, Marta, primary, Díez-Villanueva, Anna, additional, Merlos-Suárez, Anna, additional, Muñoz, Mar, additional, Lois, Sergi, additional, Carriò, Elvira, additional, Jordà, Mireia, additional, Bigas, Anna, additional, Batlle, Eduard, additional, and Peinado, Miguel A., additional
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- 2015
- Full Text
- View/download PDF
21. Conserved Mechanisms of Tumorigenesis in the Drosophila Adult Midgut
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Martorell, Òscar, primary, Merlos-Suárez, Anna, additional, Campbell, Kyra, additional, Barriga, Francisco M., additional, Christov, Christo P., additional, Miguel-Aliaga, Irene, additional, Batlle, Eduard, additional, Casanova, Jordi, additional, and Casali, Andreu, additional
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- 2014
- Full Text
- View/download PDF
22. Metabolic Alterations and Increased Liver mTOR Expression Precede the Development of Autoimmune Disease in a Murine Model of Lupus Erythematosus
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Vilà, Laia, primary, Roglans, Núria, additional, Baena, Miguel, additional, Barroso, Emma, additional, Alegret, Marta, additional, Merlos, Manuel, additional, and Laguna, Juan C., additional
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- 2012
- Full Text
- View/download PDF
23. Conserved Mechanisms of Tumorigenesis in the Drosophila Adult Midgut.
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Martorell, Òscar, Merlos-Suárez, Anna, Campbell, Kyra, Barriga, Francisco M., Christov, Christo P., Miguel-Aliaga, Irene, Batlle, Eduard, Casanova, Jordi, and Casali, Andreu
- Subjects
- *
COLON cancer , *NEOPLASTIC cell transformation , *DROSOPHILA , *CANCER invasiveness , *CELLULAR signal transduction , *EPITHELIAL cells , *CANCER cell differentiation , *ADULTS , *INTESTINAL cancer - Abstract
Whereas the series of genetic events leading to colorectal cancer (CRC) have been well established, the precise functions that these alterations play in tumor progression and how they disrupt intestinal homeostasis remain poorly characterized. Activation of the Wnt/Wg signaling pathway by a mutation in the gene APC is the most common trigger for CRC, inducing benign lesions that progress to carcinomas due to the accumulation of other genetic alterations. Among those, Ras mutations drive tumour progression in CRC, as well as in most epithelial cancers. As mammalian and Drosophila's intestines share many similarities, we decided to explore the alterations induced in the Drosophila midgut by the combined activation of the Wnt signaling pathway with gain of function of Ras signaling in the intestinal stem cells. Here we show that compound Apc-Ras clones, but not clones bearing the individual mutations, expand as aggressive intestinal tumor-like outgrowths. These lesions reproduce many of the human CRC hallmarks such as increased proliferation, blockade of cell differentiation and cell polarity and disrupted organ architecture. This process is followed by expression of tumoral markers present in human lesions. Finally, a metabolic behavioral assay shows that these flies suffer a progressive deterioration in intestinal homeostasis, providing a simple readout that could be used in screens for tumor modifiers or therapeutic compounds. Taken together, our results illustrate the conservation of the mechanisms of CRC tumorigenesis in Drosophila, providing an excellent model system to unravel the events that, upon mutation in Apc and Ras, lead to CRC initiation and progression. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
24. Metabolic alterations and increased liver mTOR expression precede the development of autoimmune disease in a murine model of lupus erythematosus.
- Author
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Laia Vilà, Núria Roglans, Miguel Baena, Emma Barroso, Marta Alegret, Manuel Merlos, and Juan C Laguna
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