Evaluación de un derivado de la Adenosina sobre la metástasis ósea inducida por el cáncer de mama

Evaluation of an Adenosine derivative on breast cancer induced bone metastasesEvaluation of an Adenosine derivative on breast cancer induced bone metastases

Citlalli Oyuki Mendoza Chacón (2024, [Tesis de maestría])

El cáncer de mama (CM) es considerado como el tipo de cáncer con mayor incidencia y la principal causa de muerte en mujeres en el mundo. Cuando el cáncer está avanzado y ha migrado a otros órganos y específicamente a los huesos, se conoce como metástasis ósea. Los tratamientos actuales ofrecen a los pacientes un panorama favorable cuando el cáncer está en estadio temprano; sin embargo, aún no existe una terapia que cure la metástasis ósea. La adenosina y sus derivados han demostrado su potencial en la regulación del crecimiento tumoral y la supervivencia de las células cancerosas. Por lo tanto, este trabajo tuvo como objetivo evaluar el potencial anticancerígeno de un derivado de la adenosina (IFC 305) sobre células de cáncer de mama 4T1 in vitro mediante ensayos de proliferación, migración, ciclo celular y apoptosis; así mismo, su efecto en un modelo in vivo de metástasis ósea. Los datos demuestran que el fármaco IFC 305 disminuye la proliferación y migración de la línea celular 4T1 dependiendo de la concentración utilizada. Por otro lado, no induce apoptosis a las 24 horas de tratamiento, pero sí un arresto del ciclo celular en la fase G0/G1. Sin embargo, el tratamiento con IFC 305 de ratones con metástasis ósea, no tuvo efecto en la disminución de las lesiones osteolíticas. Estudios futuros son necesarios para optimizar la dosis y tratamiento necesario para el modelo in vivo. En conclusión, nuestro trabajo demostró el potencial anticancerígeno del IFC 305 en ensayos in vitro, a través de la inhibición del crecimiento celular y la migración de las células cancerígenas, y sienta las bases para futuros estudios in vivo que demuestren su potencial terapéutico para el tratamiento de la metástasis ósea causada por el cáncer de mama.

Breast cancer is the type of cancer with the highest incidence and the leading cause of death in women due to this condition. When cancer cells migrate to other organs, especially bones, it is known as bone metastasis. Although the prognosis for some patients may be favorable due to early detection and treatment, there is still no therapy to cure bone metastasis by breast cancer. Adenosine and its derivatives have demonstrated their relevance in controlling proliferation, immune response, and apoptosis in different types of cancer. In this project, the anticancer potential of the drug IFC 305, a derivative of adenosine, on bone metastasis induced by breast cancer was evaluated both in vitro and in vivo. To evaluate the effect of IFC 305 on cell proliferation and migration of the 4T1 murine breast cancer cell line, the MTT assay and wound healing assay were used, respectively. The drug inhibited the proliferation and migration of 4T1 cells in a dose-dependent manner. To understand the underlying mechanism, apoptosis and the cell cycle were analyzed by flow cytometry. Results showed that after 24 hours of exposure to the drug, the effect on apoptosis is minimal. However, it was found that 4T1 cells were arrested in the G0/G1 phase of the cell cycle. However, IFC 305 treatment of mice with bone metastasis did not reduce osteolytic lesions. Future studies are necessary to optimize the dose and treatment necessary for the in vivo model. In conclusion, our work demonstrates the anticancer potential of IFC 305 on in vitro assays, through the inhibition of cell growth and migration of cancer cells. These studies seed the bases for future in vivo studies that demonstrate the IFC 305 therapeutic potential for the treatment of bone metastasis caused by breast cancer.

cáncer de mama, tratamientos, derivado de adenosina, metástasis Breast cancer, treatments, adenosine derivate, metastasis BIOLOGÍA Y QUÍMICA CIENCIAS DE LA VIDA BIOLOGÍA CELULAR OTRAS OTRAS

DES/NORMALIZAR EL ENVENENAMIENTO. ATENCIÓN, PREVENCIÓN Y REPARACIÓN ENTRE CUIDADORES FAMILIARES Y COMUNITARIOS FRENTE AL CÁNCER CAUSADO POR LA INDUSTRIA DEL ASBESTO EN SAN PEDRO BARRIENTOS

Verónica Sayuri Gallardo Kishi (2023, [Tesis de maestría])

“La presente tesis explora el diseño, descripción, análisis y hallazgos de la investigación respecto a los procesos de normalización y desnormalización del envenenamiento en San Pedro Barrientos (SPB), una problemática profunda que tiene a los cánceres por asbesto como uno de los puntos más crudos y brutales. En la breve presentación doy a conocer la estructura de la tesis, y algunas reflexiones iniciales sobre mi implicación en el trabajo de campo y respecto a la antropología encarnada. La primera parte de la tesis está compuesta por dos capítulos; en el primer capítulo desarrollo el contexto de producción de la investigación y la relevancia que tuvo la convergencia de cinco grandes procesos organizativos para establecer las condiciones de posibilidad del Proyecto de Investigación-Incidencia en SPB y con ello mi aproximación al tema. Reconozco así el modo en que estas genealogías influyeron en el desarrollo, el diseño metodológico de la investigación, expongo el planteamiento del problema, el desarrollo, el diseño metodológico de la investigación y la delimitación de actores en el cual se corresponde con la propuesta teórica en tanto relacional, ecológica, con un énfasis en la observación y participación. En el segundo capítulo formulo el encuadre teórico-conceptual de la investigación el cual, partiendo del enfoque relacional de la antropología médica crítica (AMC), busca describir, analizar y establecer relaciones entre las prácticas de prevención, reparación y atención con bastante centralidad la ecología política del problema de investigación y lo que denominaré como la ecología política de la enfermedad y las prácticas y representaciones del proceso de salud-enfermedad-atención-prevención-reparación (p-s-e-a-p-r) el cual está nutrido de los prolíficos estudios desde la ecología política en salud, una subdisciplina de la ecología política con una larga trayectoria articulando procesos de salud enfermedad con elementos ecológico-políticos”.

Cáncer - Prevención. Condiciones precancerosas. Trabajadores expuestos a asbesto. Asbesto - Efectos fisiológicos. Seguridad laboral - México - San Pedro Barrientos, Tlalnepantla de Báez. Industria del asbesto - Aspectos sanitarios - Estado de México - Tlalnepantla de Báez. Tesis - Maestría en Antropología Social, CDMX. CIENCIAS SOCIALES SOCIOLOGÍA PROBLEMAS SOCIALES ENFERMEDAD ENFERMEDAD

Chronic toxicity of shrimp feed added with silver nanoparticles (Argovit-4®) in Litopenaeus vannamei and immune response to white spot syndrome virus infection

Carlos Rosendo Romo Quiñonez Píndaro Álvarez Ruiz CLAUDIO HUMBERTO MEJIA RUIZ NINA BOGDANCHIKOVA Alexey Pestryakov CARINA GAMEZ JIMENEZ WENCESLAO VALENZUELA QUIÑONEZ Magnolia Montoya Mejía EUSEBIO NAVA PEREZ (2022, [Artículo])

"In recent years, the application of silver nanoparticles (AgNPs) as antibacterial compounds has been widely used in human and veterinary medicine. In this work, we investigated the effects of AgNPs (Argovit-4 R ) as feed additives (feed-AgNPs) on shrimp (Litopenaeus vannamei) using three different methods: 1) chronic toxicity after 28 days of feeding, 2) Effects against white spot syndrome virus (WSSV) challenged by oral route, and 3) transcriptional responses of immune-related genes (PAP, ProPO, CTL-3, Crustin, PEN3, and PEN4) following WSSV infection. The results showed that the feed-AgNPs did not interfere with the growth and survival of shrimp. Also, mild lesions in the hepatopancreas were recorded, proportional to the frequency of the feed-AgNP supply. Challenge test versus WSSV showed that feeding every 7 days with feed-AgNPs reduced mortality, reaching a survival rate of 53%, compared to the survival rates observed in groups fed every 4 days, daily and control groups of feed-AgNPs for the 30%, 10%, and 7% groups, respectively. Feed-AgNPs negatively regulated the expression of PAP, ProPO, and Crustin genes after 28 days of treatment and altered the transcriptional responses of PAP, ProPO, CTL-3, and Crustin after WSSV exposure. The results showed that weekly feeding-AgNPs could partially prevent WSSV infection in shrimp culture. However, whether or not transcriptional responses against pathogens are advantageous remains to be elucidated."

Silver nanoparticles, Shrimp, Aquaculture, Chronic toxicity, WSSV, AgNP, Argovit, Litopenaeus vannamei , Silver fed, White spot syndrome virus BIOLOGÍA Y QUÍMICA CIENCIAS DE LA VIDA INMUNOLOGÍA INMUNIZACIÓN INMUNIZACIÓN

Enhancement of antibiotics antimicrobial activity due to the silver nanoparticles impact on the cell membrane

Roberto Vazquez-Munoz (2019, [Artículo])

The ability of microorganisms to generate resistance outcompetes with the generation of new and efficient antibiotics; therefore, it is critical to develop novel antibiotic agents and treatments to control bacterial infections. An alternative to this worldwide problem is the use of nanomaterials with antimicrobial properties. Silver nanoparticles (AgNPs) have been extensively studied due to their antimicrobial effect in different organisms. In this work, the synergistic antimicrobial effect of AgNPs and conventional antibiotics was assessed in Gram-positive and Gram-negative bacteria. AgNPs minimal inhibitory concentration was 10–12 μg mL-1 in all bacterial strains tested, regardless of their different susceptibility against antibiotics. Interestingly, a synergistic antimicrobial effect was observed when combining AgNPs and kanamycin according to the fractional inhibitory concentration index, FICI: <0.5), an additive effect by combining AgNPs and chloramphenicol (FICI: 0.5 to 1), whereas no effect was found with AgNPs and β-lactam antibiotics combinations. Flow cytometry and TEM analysis showed that sublethal concentrations of AgNPs (6–7 μg mL-1) altered the bacterial membrane potential and caused ultrastructural damage, increasing the cell membrane permeability. No chemical interactions between AgNPs and antibiotics were detected. We propose an experimental supported mechanism of action by which combinatorial effect of antimicrobials drives synergy depending on their specific target, facilitated by membrane alterations generated by AgNPs. Our results provide a deeper understanding about the synergistic mechanism of AgNPs and antibiotics, aiming to combat antimicrobial infections efficiently, especially those by multi-drug resistant microorganisms, in order to mitigate the current crisis due to antibiotic resistance. © 2019 Vazquez-Muñoz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ampicillin, antibiotic agent, aztreonam, beta lactam antibiotic, biapenem, chloramphenicol, kanamycin, silver nanoparticle, silver nitrate, antiinfective agent, metal nanoparticle, silver, antibiotic sensitivity, antimicrobial activity, Article, bact BIOLOGÍA Y QUÍMICA CIENCIAS DE LA VIDA BIOFÍSICA BIOFÍSICA

Dual function of EDTA with silver nanoparticles for root canal treatment–A novel modification

JUAN MANUEL MARTINEZ ANDRADE (2018, [Artículo])

The chelating and antimicrobial capacity of a novel modification of 17% EDTA with silver nanoparticles (AgNPs) (EDTA-AgNPs) was evaluated in-vitro for root canal treatment (RCT). The EDTA-AgNPs solution was characterized by UV-Vis spectroscopy, ?-potential and high-resolution transmission electron microscopy (HRTEM). Antimicrobial capacity was evaluated against Candida albicans and Staphylococcus aureus in planktonic and biofilm cells by broth macrodilution (24 h) and XTT assays, (1, 10 and 30 min) respectively. The chelating capacity of EDTA-AgNPs was assessed indirectly (smear layer removal) and directly (demineralizing effect) in bovine dentin at two silver concentrations, 16 and 512 ?g/ ml at 1 and 10 minutes of exposure time. Smear layer removal was evaluated by atomic force microscopy (AFM) and scanning electron microscopy (SEM). The demineralizing effect was determined by atomic absorption spectroscopy (AAS), microhardness test (MH) and X-ray diffractometer (XRD). Synthesized AgNPs were quasi-spherical in shape with an average size of 13.09 ± 8.05 nm. 17% EDTA-AgNPs was effective to inhibit C. albicans and S. aureus in planktonic and biofilm cultures. The smear layer removal and demineralizing effect were similar between 17% EDTA-AgNPs and 17% EDTA treatments. The 17% EDTA-AgNPs solution proved to be an effective antimicrobial agent, and has a similar chelating capacity to 17% EDTA alone. These in-vitro studies strongly suggest that EDTA-AgNPs could be used for effective smear layer removal, having an antimicrobial effect at the same time during RCT. © 2018 Martinez-Andrade et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

edetic acid, silver nanoparticle, edetic acid, metal nanoparticle, silver, antibacterial activity, antibiotic sensitivity, antifungal activity, antimicrobial activity, Article, atomic absorption spectrometry, atomic force microscopy, biofilm, bovine, BIOLOGÍA Y QUÍMICA CIENCIAS DE LA VIDA MICROBIOLOGÍA MICROBIOLOGÍA

Desarrollo de nanocompositos de cápside viral P22 para la terapia con profármacos enzimáticos en cáncer de mama

Development of P22 viral capsid nanocomposites for enzymatic prodrug therapy in breast cancer

Astrid Rebeca Luna Rios (2024, [Tesis de maestría])

Las estrategias actuales contra el cáncer de mama presentan limitaciones debido a la falta de selectividad, disminuyendo su efectividad. La mayoría de los fármacos, como el tamoxifeno, requieren la activación metabólica por parte de las enzimas de la familia citocromo P450 (CYP) para ejercer mayores efectos anticancerígenos. Sin embargo, la concentración del CYP es variable y baja en las células tumorales, especialmente en el cáncer de mama, lo que provoca efectos secundarios. En la terapia de activación enzimática de profármacos (EPT), las enzimas se dirigen al tumor para transformar el profármaco, lo que normalmente implica la administración de la enzima seguida del profármaco. Sin embargo, las diferencias entre la farmacocinética y farmacodinamia son un obstáculo para mejorar el tratamiento. Por lo tanto, la administración conjunta de profármaco y enzima es esencial para garantizar su interacción favorable en el tumor. Este trabajo reporta una nueva clase de nanocompositos terapéuticos basados en partículas tipo virus P22 confinando CYP, funcionalizadas superficialmente con glucosa oxidasa (GOx) que transforma la glucosa en D-glucono-δ-lactona produciendo H2O2, el aceptor final de electrones en la transformación de tamoxifeno mediado por CYP, y conjugadas con un derivado de tamoxifeno como profármaco y ligando dirigido utilizando polietilenglicol como conector. En un microambiente tumoral rico en glucosa, estos nanocompuestos pueden producir fármaco activo in situ. Se caracterizaron las propiedades fisicoquímicas y la catálisis secuencial mediada por glucosa de los nanocompositos. Los estudios in vitro demostraron una disminución en la viabilidad celular en líneas celulares de cáncer de mama ER+ y ER-. Sin embargo, la internalización celular en ausencia de glucosa mostró ser preferencial con las VLPs dirigidas en ambas líneas celulares. La administración conjunta de enzimas y profármacos con una localización mejorada de las VLPs desarrolladas después de la funcionalización del tamoxifeno, lo que sugiere el potencial de los nanocompositos desarrollados para superar los desafíos existentes de la EPT y mejorar los resultados terapéuticos con efectos secundarios reducidos.

Current treatment strategies against breast cancer have limitations due to lack in selectivity. Most drugs, such as tamoxifen, require metabolic activation by cytochrome P450 (CYP) enzymes to perform greater anticancer effects. However, the concentration of CYP varies and is low in tumor cells, especially in breast cancer, resulting in side-effects. In enzyme prodrug therapy (EPT), enzymes are targeted to the tumor cells for prodrug transformation, typically involving the sequential delivery of the enzyme followed by the prodrug. However, differences in pharmacokinetics and pharmacodynamics are a major hindrance for improving treatment. Therefore, co-delivery of prodrug and enzyme is essential to ensure their favorable interaction in tumor. This work reports a new class of therapeutic nanocomposites based on P22 virus like particles (VLPs) confining the CYP activity, surface functionalized with glucose oxidase (GOx) that transforms glucose into D-glucono-δ-lactone producing hydrogen peroxide, the final electron acceptor in the CYP-mediated transformation of tamoxifen, and together conjugated with a tamoxifen derivative as prodrug and targeting ligand using polyethylene glycol as a linker. In glucose-rich tumor microenvironment, these nanocomposites can produce active drug in situ. The physicochemical properties and sequential glucose-mediated catalysis of the nanocomposites were characterized. In vitro studies demonstrated a decrease in cell viability in both ER+ and ER- breast cancer cell lines. However, cellular internalization in the absence of glucose showed improved uptake of targeted VLPs in both cell lines. The co-delivery of enzymes and prodrug with improved localization of developed VLPs after tamoxifen functionalization, suggests the potential of developed nanocomposites to overcome the existing challenges of EPT and improve the therapeutic outcomes with reduced side effects.

VLP-P22, Citocromo P45O, Glucosa oxidasa, Tamoxifeno, Terapia de activación enzimática de profármacos VLP-P22, Cytochrome P45O, Glucose oxidase, Tamoxifen, Enzyme prodrug therapy BIOLOGÍA Y QUÍMICA QUÍMICA QUÍMICA FARMACÉUTICA DISEÑO.SÍNTESIS Y ESTUDIO NUEVOS FÁRMACOS DISEÑO.SÍNTESIS Y ESTUDIO NUEVOS FÁRMACOS

Effect of antimicrobial nanocomposites on Vibrio cholerae lifestyles: Pellicle biofilm, planktonic and surface-attached biofilm

ANAID MEZA VILLEZCAS (2019, [Artículo])

Vibrio cholerae is an important human pathogen causing intestinal disease with a high incidence in developing countries. V. cholerae can switch between planktonic and biofilm lifestyles. Biofilm formation is determinant for transmission, virulence and antibiotic resistance. Due to the enhanced antibiotic resistance observed by bacterial pathogens, antimicrobial nanomaterials have been used to combat infections by stopping bacterial growth and preventing biofilm formation. In this study, the effect of the nanocomposites zeolite-embedded silver (Ag), copper (Cu), or zinc (Zn) nanoparticles (NPs) was evaluated in V. cholerae planktonic cells, and in two biofilm states: pellicle biofilm (PB), formed between air-liquid interphase, and surface-attached biofilm (SB), formed at solid-liquid interfaces. Each nanocomposite type had a distinctive antimicrobial effect altering each V. cholerae lifestyles differently. The ZEO-AgNPs nanocomposite inhibited PB formation at 4 μg/ml, and prevented SB formation and eliminated planktonic cells at 8 μg/ml. In contrast, the nanocomposites ZEO-CuNPs and ZEO-ZnNPs affect V. cholerae viability but did not completely avoid bacterial growth. At transcriptional level, depending on the nanoparticles and biofilm type, nanocomposites modified the relative expression of the vpsL, rbmA and bap1, genes involved in biofilm formation. Furthermore, the relative abundance of the outer membrane proteins OmpT, OmpU, OmpA and OmpW also differs among treatments in PB and SB. This work provides a basis for further study of the nanomaterials effect at structural, genetic and proteomic levels to understand the response mechanisms of V. cholerae against metallic nanoparticles. © 2019 Meza-Villezcas et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

bacterial protein, copper nanoparticle, nanocomposite, OmpT protein, OmpU protein, OmpW protein, outer membrane protein A, silver nanoparticle, unclassified drug, zeolite, zinc nanoparticle, antiinfective agent, copper, metal nanoparticle, nanocompos BIOLOGÍA Y QUÍMICA CIENCIAS DE LA VIDA MICROBIOLOGÍA MICROBIOLOGÍA