Authors: Simian, Marina; Manzur, Teresita; Rodriguez, Vanina; Bal, Elisa Dora; Klein, Slobodanka Mariana
Publication Date: 2009.
Language: English.
Abstract:
Currently, an in vivo spontaneous model of estrogen dependent, tamoxifen sensitive breast cancer does not exist. We show here the characterization of the M05 mammary tumor that appeared spontaneously in a 1-year-old virgin female BALB/c mouse in our animal facility. The M05 tumor is a semi-differentiated adenocarcinoma that expresses estrogen and progesterone receptors. When it was transplanted to either male or ovariectomized female mice it did not grow. Moreover, ovariectomy or treatment with tamoxifen of tumor bearing mice led to a halt in tumor growth. Treatment of ovariectomized mice that had been inoculated with the M05 tumor showed that only estradiol, but not progesterone, promoted the re-growth of the tumor. Finally, after passage nine, tumor growth was achieved in male and ovariectomized female mice suggesting that the tumor had progressed to hormone independence. However, like often found in the clinic, expression of estrogen and progesterone receptors was maintained. This model mimics the biology of estrogen receptor positive breast cancer in humans and presents itself as an invaluable tool for the study of endocrine resistance in a physiologically relevant setting.
Author affiliation: Simian, Marina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Author affiliation: Manzur, Teresita. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina
Author affiliation: Rodriguez, Vanina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina
Author affiliation: Bal, Elisa Dora. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Author affiliation: Klein, Slobodanka Mariana. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Repository: CONICET Digital (CONICET). Consejo Nacional de Investigaciones Científicas y Técnicas
Authors: Orlando, Ulises Daniel; Castillo, Ana Fernanda; Dattilo, Melina A.; Solano, Angela Rosario; Maloberti, Paula Mariana; Podesta, Ernesto Jorge
Publication Date: 2015.
Language: English.
Abstract:
Although the role of acyl-CoA synthetase 4 (ACSL4) in mediating an aggressive phenotype is well accepted, there is little evidence as to the early steps through which ACSL4 increases tumor growth and progression. In this study, and by means of the stable transfection of MCF-7 cells with ACSL4 using the tetracycline Tet-Off system (MCF-7 TetOff/ACSL4), we identify the mTOR pathway as one of the main specific signatures of ACSL4 expression and demonstrate the partial involvement of the lipoxygenase pathway in the activation of mTOR. The specificity of ACSL4 action on mTOR signaling is also determined by doxycycline inhibition of ACSL4 expression in MCF-7 Tet-Off/ACSL4 cells, by the expression of ACSL4 in the non-aggressive T47D breast cancer cell line and by knocking down this enzyme expression in the MDA-MB-231 breast cancer cells, which constitutively express ACSL4. ACSL4 regulates components of the two complexes of the mTOR pathway (mTORC1/2), along with upstream regulators and substrates. We show that mTOR inhibitor rapamycin and ACSL4 inhibitor rosiglitazone can act in combination to inhibit cell growth. In addition, we demonstrate a synergistic effect on cell growth inhibition by the combination of rosiglitazone and tamoxifen, an estrogen receptor α (ERα) inhibitor. Remarkably, this synergistic effect is also evident in the triple negative MDA-MB-231 cells in vitro and in vivo. These results suggest that ACSL4 could be a target to restore tumor hormone dependence in tumors with poor prognosis for disease-free and overall survival, in which no effective specifically targeted therapy is readily available.
Author affiliation: Orlando, Ulises Daniel. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquimica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina
Author affiliation: Castillo, Ana Fernanda. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquimica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina
Author affiliation: Dattilo, Melina A.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquimica; Argentina
Author affiliation: Solano, Angela Rosario. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquimica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina
Author affiliation: Maloberti, Paula Mariana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquimica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina
Author affiliation: Podesta, Ernesto Jorge. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquimica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina
Repository: CONICET Digital (CONICET). Consejo Nacional de Investigaciones Científicas y Técnicas
Authors: Morvillo, V.; Luthy, Isabel Alicia; Bravo, A. I.; Capurro, M. I.; Portela, P.; Calandra, Ricardo Saul; Mordoh, Jose
Publication Date: 2002.
Language: English.
Abstract:
The presence and characteristics of androgen receptors (AR) have been described by our group in one human melanoma cell line. We now investigated their presence in two other human melanoma cell lines, IIB-MEL-LES and IIB-MEL-IAN, as well as in biopsies of human metastatic melanoma. Scatchard analysis revealed a single binding component for both cell lines, the apparent dissociation constant obtained being 15 nM, with a binding capacity of 280 fmol/mg total cell protein for IIB-MEL-LES cells and of 14 nM with a binding capacity of 206 fmol/mg total cell protein for IIB-MEL-IAN. When specificity was assessed, as seen before, not only androgen and antiandrogen, but also non-androgenic compounds were able to compete for [3H]-R1881 binding. When immunocytochemistry of IIB-MEL-LES and IIB-MEL-IAN cells was performed for AR, both cell lines were deeply stained in the nucleus whereas no staining was found for oestrogen and progesterone receptors. Every specimen of melanoma metastases tested for the presence of AR was deeply stained, and the intensity of the staining was high in the majority. Several hormones and antihormones were tested for their ability to affect cell proliferation. On both cell lines, Testosterone, Dihydrotesterone, Oestradiol and Progesterone significantly stimulated cell proliferation, with reversion by Hydroxy-Flutamide, Casodex or Tamoxifen.
Author affiliation: Morvillo, V.. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Author affiliation: Luthy, Isabel Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Author affiliation: Bravo, A. I.. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos ; Argentina
Author affiliation: Capurro, M. I.. Instituto Luis Federico Leloir;
Author affiliation: Portela, P.. Instituto Luis Federico Leloir;
Author affiliation: Calandra, Ricardo Saul. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas; Argentina
Author affiliation: Mordoh, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Repository: CONICET Digital (CONICET). Consejo Nacional de Investigaciones Científicas y Técnicas
Authors: Lamb, Caroline Ana; Helguero, Luisa A.; Fabris, Victoria Teresa; Colombo, Lucas Luis; Molinolo, Alfredo; Lanari, Claudia Lee Malvina
Publication Date: 2003.
Language: English.
Abstract:
The purpose of this study was to evaluate the effect of the selective estrogen receptor modulators raloxifene and tamoxifen and of the pure antiestrogen fulvestrant on tumor growth and progesterone receptor (PR) expression in an experimental model of breast cancer. The effects of these compounds on cell proliferation were studied in primary cultures of a progestin-dependent mammary carcinoma tumor line, in the presence of medroxyprogesterone acetate (MPA) or 17-β-estradiol (E2). In in vivo studies the tumor was inoculated subcutaneously in BALB/c female mice treated with 20 mg MPA depot. Raloxifene (12.5 mg/kg) or tamoxifen (5 mg/kg) were administered in daily doses or E2 silastic pellets (5 mg) were implanted. When the tumors reached about 25–50 mm2 MPA was removed in half of the animals. E2 induced complete tumor regressions, tamoxifen inhibited tumor growth in vivo while raloxifene disclosed proliferative effects in animals in which MPA had been removed. In vitro, E2 inhibited cell proliferation at concentrations higher than 10−14 M. Raloxifene and fulvestrant, but not tamoxifen, partially reverted E2-induced inhibition. Fulvestrant and tamoxifen inhibited MPA-induced cell proliferation while raloxifene had a stimulatory effect. Tamoxifen and E2 increased, raloxifene induced no effect, and fulvestrant significantly decreased PR expression. In this study we provide evidence for differential effects of tamoxifen and raloxifene on experimental mammary tumors. Since raloxifene is under evaluation for use in breast cancer prevention, these results may have important clinical implications.
Author affiliation: Lamb, Caroline Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Author affiliation: Helguero, Luisa A.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Author affiliation: Fabris, Victoria Teresa. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Author affiliation: Colombo, Lucas Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Author affiliation: Molinolo, Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Author affiliation: Lanari, Claudia Lee Malvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Repository: CONICET Digital (CONICET). Consejo Nacional de Investigaciones Científicas y Técnicas
Authors: Muthular, Milagros; Passero, Pablo; Jewtuchowicz, Virginia; Miozza, Valeria; Brusca, María Isabel; Pérez, Cristina
Publication Date: 2018.
Language: Spanish.
Abstract:
Candida albicans es uno de los microorganismos más frecuentemente involucrados en diversas infecciones y podría provenir de la cavidad bucal del paciente, tanto de nichos de caries como de enfermedad periodontal. El desarrollo de resistencia a los medicamentos disponibles y otros factores justifican la búsqueda de nuevas alternativas antimicóticas. Objetivo. Estudiar en forma comparativa los efectos in vitro del medicamento antitumoral tamoxifeno (Tx) y del fluconazol (Flz) sobre el crecimiento de cepas clínicas de Candida albicans aisladas de la boca de pacientes con patologías odontológicas y médicas. Materiales y métodos. Se emplearon siete cepas de C. albicans: a) una estándar ATCC 90028 sensible a Flz (ATCC); b) cuatro bucales de sendas pacientes oncológicas con enfermedad periodontal (period 8, 9, 10 y 11); c) dos bucales de un paciente con SIDA y candidiasis orofaríngea: c1) una sensible a Flz (2-76) y c2) una resistente a Flz (12-99). Se evaluó el crecimiento celular y la concentración inhibitoria mínima (CIM) por técnicas del M27-A3, CLSI. Se calculó la concentración inhibitoria 50 % (CI50) por análisis informático de funciones. Resultados. El tamoxifeno inhibió el crecimiento de Candida albicans, tanto sensible como resistente al fluconazol. Los datos se ajustan adecuadamente a curvas teóricas saturables de tipo concentración del inhibidor versus respuesta. La potencia del tamoxifeno con respecto al tamoxifeno es 31veces mayor sobre la cepa resistente y menor que 1 en las sensibles. Conclusiones. El tamoxifeno tiene actividad antimicótica sobre cepas bucales aisladas de pacientes con patologías odontológicas y médicas. Reviste particular interés su potencia sobre la cepa resistente al fluconazol
Author affiliation: Muthular, Milagros. Universidad de Buenos Aires
Author affiliation: Passero, Pablo . Universidad de Buenos Aires
Author affiliation: Jewtuchowicz, Virginia. Universidad de Buenos Aires
Author affiliation: Miozza, Valeria. Universidad de Buenos Aires
Author affiliation: Brusca, María Isabel. Universidad de Buenos Aires
Author affiliation: Pérez, Cristina. Universidad de Buenos Aires
Keywords: Odontología; Azoles; Tamoxifeno; Candida albicans; Enfermedades de la boca.
Repository: Biblioteca Digital (UNCu). Universidad Nacional de Cuyo
Authors: Piñero, Tamara Alejandra; Landoni, Malena; Duschak, Vilma Gladys; Katzin, Alejandro M.; Couto, Alicia Susana
Publication Date: 2018.
Language: English.
Abstract:
Parasites of the genus Plasmodium responsible for Malaria are obligate intracellular pathogens residing in mammalian red blood cells, hepatocytes, or mosquito midgut epithelial cells. Regarding that detailed knowledge on the sphingolipid biosynthetic pathway of the apicomplexan protozoan parasites is scarce, different stages of Plasmodium falciparum were treated with tamoxifen in order to evaluate the effects of this drug on the glycosphingolipid biosynthesis. Thin layer chromatography, High performance reverse phase chromatography and UV-MALDI-TOF mass spectrometry were the tools used for the analysis. In the ring forms, the increase of NBD-phosphatidyl inositol biosynthesis was notorious but differences at NBD-GlcCer levels were undetectable. In trophozoite forms, an abrupt decrease of NBD-acylated GlcDHCer and NBD-GlcDHCer in addition to an increase of NBD-PC biosynthesis was observed. On the contrary, in schizonts, tamoxifen seems not to be producing substantial changes in lipid biosynthesis. Our findings indicate that in this parasite, tamoxifen is exerting an inhibitory action on Glucosylceramidesynthase and sphingomyelin synthase levels. Moreover, regarding that Plasmodium does not biosynthesize inositolphosphoceramides, the accumulation of phosphatidylinositol should indicate an inhibitory action on glycosylinositol phospholipid synthesis.
Author affiliation: Piñero, Tamara Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones en Hidratos de Carbono; Argentina
Author affiliation: Landoni, Malena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones en Hidratos de Carbono; Argentina
Author affiliation: Duschak, Vilma Gladys. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C. G. Malbrán”. Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben”; Argentina
Author affiliation: Katzin, Alejandro M.. Universidade de Sao Paulo; Brasil
Author affiliation: Couto, Alicia Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones en Hidratos de Carbono; Argentina
Repository: CONICET Digital (CONICET). Consejo Nacional de Investigaciones Científicas y Técnicas
Authors: Ramos, Jorge Guillermo; Varayoud, Jorgelina Guadalupe; Kass, Laura; Rodriguez, Horacio Adolfo; Muñoz de Toro, Monica Milagros; Montes, Gregorio S.; Luque, Enrique Hugo
Publication Date: 2000.
Language: English.
Abstract:
Ripening of the rat cervix involves widespread collagenolysis that follows an eosinophilic leukocyte infiltration. The hormonal control of these events is not well understood. The aims of this study were to investigate the mechanism through which progesterone (P) and 17β-estradiol (E2) modulate eosinophilic invasion and to determine if this event is protein synthesis mediated. Cervical eosinophilic invasion was measured in intact rats during the second half of pregnancy and compared with values from ovariectomized (O) pseudopregnant (PSP) rats treated with P and E2 in doses that mimicked the levels of pregnancy. Other O-PSP rats were treated with an E2 antagonist (tamoxifen) and the antiprogestin RU-486. To study the role of protein synthesis in eosinophilic invasion of the cervix, rats were treated with actinomycin-D (an inhibitor of mRNA synthesis), and animals were sacrificed on D21 or D22 to evaluate eosinophilic invasion. Rats treated with E2 showed high levels of infiltration and tamoxifen blocked this E2 effect. On the other hand, P antagonized the stimulatory effects of E2 on eosinophilic invasion, however when the P and E2 treated rats were injected with RU-486 the inhibitory effect of P was reversed. In intact pregnant rats a sharp rise in eosinophilic infiltration was detected on D23, 20 h after the fall of serum P. Finally, E2 treated rats injected with actinomycin-D had no invasion of eosinophils. In conclusion, the estrogen-triggered eosinophil invasion is affected by the classic estrogen receptor antagonist tamoxifen and by the mRNA synthesis blocker actinomycin-D suggesting a genomic action of E2. Furthermore, the estrogen effect is blocked by P and this inhibition is reversed by RU-486. Copyright (C) 2000 Elsevier Science Inc.
Author affiliation: Ramos, Jorge Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina
Author affiliation: Varayoud, Jorgelina Guadalupe. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina
Author affiliation: Kass, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina
Author affiliation: Rodriguez, Horacio Adolfo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina
Author affiliation: Muñoz de Toro, Monica Milagros. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina
Author affiliation: Montes, Gregorio S.. The University of São Paulo School of Medicine; Brasil
Author affiliation: Luque, Enrique Hugo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina
Repository: CONICET Digital (CONICET). Consejo Nacional de Investigaciones Científicas y Técnicas
Authors: Nicolao, María Celeste; Elissondo, María Celina; Denegri, Guillermo Maria; Goya, Alejandra Beatriz; Cumino, Andrea Carina
Publication Date: 2014.
Language: English.
Abstract:
Cystic echinococcosis is a zoonotic infection caused by the larval stage of the cestode Echinococcus granulosus. Chemotherapy currently employs benzimidazoles; however, 40% of cases do not respond favorably. With regard to these difficulties, novel therapeutic tools are needed to optimize treatment in humans. The aim of this work was to explore the in vitro and in vivo effects of tamoxifen (TAM) against E. granulosus. In addition, possible mechanisms for the susceptibility of TAM are discussed in relation to calcium homeostasis, P-glycoprotein inhibition, and antagonist effects on a putative steroid receptor. After 24 h of treatment, TAM, at a low micromolar concentration range (10 to 50 μM), inhibited the survival of E. granulosus protoscoleces and metacestodes. Moreover, we demonstrated the chemotherapeutic and chemopreventive pharmacological effects of the drug. At a dose rate of 20 mg/kg of body weight, TAM induced protection against the infection in mice. In the clinical efficacy studies, a reduction in cyst weight was observed after the administration of 20 mg/kg in mice with cysts developed during 3 or 6 months, compared to that of those collected from control mice. Since the collateral effects of high TAM doses have been largely documented in clinical trials, the use of low doses of this drug as a short-term therapy may be a novel alternative approach for human cystic echinococcosis treatment.
Author affiliation: Nicolao, María Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Biologia. Laboratorio de Zoonosis Parasitarias; Argentina
Author affiliation: Elissondo, María Celina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Biologia. Laboratorio de Zoonosis Parasitarias; Argentina
Author affiliation: Denegri, Guillermo Maria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Biologia. Laboratorio de Zoonosis Parasitarias; Argentina
Author affiliation: Goya, Alejandra Beatriz. Ministerio de Agricultura, Ganadería, Pesca y Alimento. Servicio Nacional de Sanidad y Calidad Agroalimentaria; Argentina
Author affiliation: Cumino, Andrea Carina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Biologia. Laboratorio de Zoonosis Parasitarias; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Química; Argentina
Repository: CONICET Digital (CONICET). Consejo Nacional de Investigaciones Científicas y Técnicas
Authors: Chevalier, Merari Tumin; Rescignano, Nicoletta; Martin Saldaña, Sergio; González Gómez, Álvaro; Kenny, José Maria; San Román, Julio; Mijangos, Carmen; Alvarez, Vera Alejandra
Publication Date: 2017.
Language: English.
Abstract:
About one-fifth of cancer patients suffer from breast cancer worldwide. Polymeric nanoparticles play an important role in delivering chemotherapeutic agents in a controlled manner. Polylysine coated tamoxifen loaded poly(lactic-co-glycolic acid) nanoparticles were prepared using a single emulsion technique with subsequent non-covalently surface functionalization in order to improve nanoparticle-cell interaction and hence tamoxifen therapeutic effect. The obtained nanoparticles were fully characterized in terms of their physico-chemical properties as well of their in vitro performance against human breast adenocarcinoma cells. The successful incorporation of tamoxifen within the hydrophobic matrix of nanoparticles is evidenced by a high loading efficiency (86%). Furthermore, ideal size, morphology and hydrodynamic properties are observed being the proposed nanocarrier capable of display a valuable antiproliferative in vitro effect.
Author affiliation: Chevalier, Merari Tumin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Ciencia y Tecnología de Materiales. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Instituto de Investigaciones en Ciencia y Tecnología de Materiales; Argentina
Author affiliation: Rescignano, Nicoletta. Instituto en Ciencia y Tecnología de Polímeros; España
Author affiliation: Martin Saldaña, Sergio. Instituto en Ciencia y Tecnología de Polímeros; España
Author affiliation: González Gómez, Álvaro. Instituto en Ciencia y Tecnología de Polímeros; España
Author affiliation: Kenny, José Maria. Università di Perugia; Italia
Author affiliation: San Román, Julio. Instituto en Ciencia y Tecnología de Polímeros; España
Author affiliation: Mijangos, Carmen. Instituto en Ciencia y Tecnología de Polímeros; España
Author affiliation: Alvarez, Vera Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Ciencia y Tecnología de Materiales. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Instituto de Investigaciones en Ciencia y Tecnología de Materiales; Argentina
Repository: CONICET Digital (CONICET). Consejo Nacional de Investigaciones Científicas y Técnicas
Publication Date: 2015.
Language: English.
Abstract:
Estrogens and tamoxifen do not only exert their effects at the genomic level, but also play a role at the cell membrane activating downstream signaling pathways. We recently characterized an estrogen receptor-positive epithelial murine breast cancer cell line, LM05-E. Utilizing this cell line and MCF-7 cells, we compared the non-genomic effects of estradiol and 4-OH-tamoxifen. We showed that, similar to estradiol, tamoxifen activated the MAPK/ERK 1/2 pathway; however, we did not find activation of PI3K/AKT by either estradiol or tamoxifen. Short-term treatments with estradiol stimulated, whereas tamoxifen inhibited cell proliferation. Using pharmacological inhibitors we showed that the effect of estradiol was mediated by the MAPK/ERK 1/2 pathway, but that inhibition of this pathway did not affect tamoxifen. Surprisingly, however, blocking of PI3K/AKT signaling interfered with the inhibitory effect of tamoxifen. Analysis of the involvement of the EGFR support previous findings that designate this receptor as a mediator of the non-genomic effects of estradiol; blocking EGFR also reverses the inhibitory effect of tamoxifen. Finally, matrix metalloproteinases (MMPs) were confirmed to be involved in the proliferative effect of estradiol. These results demonstrated the novel non-genomic effects of tamoxifen and revealed that pathways downstream of EGFR and PI3K/AKT are involved in the inhibition of cell proliferation. Caution should be exercised when analyzing strategies that aim at combining endocrine therapy with specific signaling inhibitors.
Author affiliation: Raffo, Diego Alejandro. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Author affiliation: Pontiggia, Osvaldo Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; Argentina
Author affiliation: Bal, Elisa Dora. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; Argentina
Author affiliation: Simian, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; Argentina
Repository: CONICET Digital (CONICET). Consejo Nacional de Investigaciones Científicas y Técnicas