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1.
Tech Coloproctol ; 25(9): 1045-1054, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34110535

RESUMEN

BACKGROUND: Minimally invasive techniques for treating pilonidal disease are safe and effective alternatives to conventional surgery, with improved recovery time, cosmetic results, and pain control. The aim of this study was to evaluate the 5-year surgical outcomes of a single-center case series treated with endoscopic pilonidal sinus treatment (EPSiT). METHODS: We conducted a retrospective single-center analysis of all patients treated with EPSiT, by a single surgical team, from March 2015 to December 2019, for primary or recurrent pilonidal disease. The primary outcomes were recurrence, persistence and treatment failure. The secondary outcomes were postoperative pain, painkiller use, time off work, satisfaction, complications, wound healing time, time to persistence or recurrence. RESULTS: Forty-two patients underwent 46 EPSiT procedures [34 males, 8 females, median age 25 (IQR 13.75) years] for primary (47.8%) or recurrent pilonidal disease (52.2%). All patients completed the follow-up [median 62 (IQR 43) months]. The single procedure healing rate was 76.1%. The healing rate for the first procedures plus the second EPSiT procedure (performed in 4 cases) was 83.3%. Among the 46 EPSiT procedures, we recorded six cases of persistence (13.0%) and five cases of recurrence (10.9%) The median operative time was 32.5 (IQR 18.75) minutes, the median pain score (visual analog scale) in week 1 was 2 (IQR 2), and the median time off work was 4 (IQR 2) days. Four patients (8.7%) experienced complications: serosanguineous (n = 2) or seropurulent discharge (n = 2). The satisfaction rate was 95.7%. CONCLUSIONS: In our experience, EPSiT is safe, well accepted. and associated with a low level of postoperative pain, short hospitalization, short time off work, as well as optimal cosmetic results. Its failure rate is similar to that of excisional surgery.


Asunto(s)
Seno Pilonidal , Adulto , Femenino , Humanos , Masculino , Recurrencia Local de Neoplasia , Dolor Postoperatorio/etiología , Seno Pilonidal/cirugía , Recurrencia , Estudios Retrospectivos , Resultado del Tratamiento
2.
G Chir ; 39(2): 114-117, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29694313

RESUMEN

INTRODUCTION: Paget disease of the nipple in man is a very rare breast cancer, and there are not standard procedures or guidelines. In any cases, a Paget's disease could hide an invasive ductal breast cancer. CASE DESCRIPTION: We report the case of a 77-years old man affected by Alzheimer's disease, who presented to our attention because of an ulcerated palpable mass in the right nipple. A biopsy of the lesion showed "intra-epidermic proliferation of epitelioid cells, associated with linfo-plasmacellular infiltration of superficial dermis, compatible with Paget's disease (pTis)". We discussed the case in the multidisciplinary meeting and decided to subject the patient to surgery, so a right mastectomy plus sentinel lymph node biopsy (SLNB) were performed. Histo-pathological examination revealed "invasive ductal carcinoma of the breast, associated with a small component of in situ ductal carcinoma and Paget's disease of the nipple with superficial ulceration". Resection margins were free. Sentinel lymph node was negative. Biological features were as follows: ER 95%, PR 60%, Her-2/neu 1+, Ki-67 35%. The patient was discharged in the third post-operative day in good conditions. In the following weeks the patient's healing process was good and free of complications. CONCLUSIONS: Clinical recognition of Paget's disease is very important also in man, because it can be the alarm bell for an underlying invasive ductal breast cancer, often more aggressive than in woman.


Asunto(s)
Neoplasias de la Mama Masculina/patología , Estrógenos , Neoplasias Hormono-Dependientes/patología , Neoplasias Primarias Múltiples/patología , Pezones/patología , Enfermedad de Paget Mamaria/patología , Progesterona , Anciano , Enfermedad de Alzheimer/complicaciones , Antineoplásicos Hormonales/uso terapéutico , Neoplasias de la Mama Masculina/complicaciones , Neoplasias de la Mama Masculina/tratamiento farmacológico , Neoplasias de la Mama Masculina/cirugía , Carcinoma Ductal de Mama/patología , Carcinoma Ductal de Mama/cirugía , Carcinoma Intraductal no Infiltrante/patología , Carcinoma Intraductal no Infiltrante/cirugía , Terapia Combinada , Humanos , Masculino , Mastectomía , Neoplasias Hormono-Dependientes/complicaciones , Neoplasias Hormono-Dependientes/tratamiento farmacológico , Neoplasias Hormono-Dependientes/cirugía , Neoplasias Primarias Múltiples/cirugía , Enfermedad de Paget Mamaria/complicaciones , Enfermedad de Paget Mamaria/etiología , Enfermedad de Paget Mamaria/cirugía , Úlcera Cutánea/etiología , Tamoxifeno/uso terapéutico
3.
J Sci Food Agric ; 96(7): 2352-65, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26212782

RESUMEN

BACKGROUND: Melon aroma volatiles were extracted at harvest from juice of a climacteric near-isogenic line (NIL) SC3-5-1 with two quantitative trait loci (QTLs) introgressed which produced climacteric behaviour and its non-climacteric parental (PS) using two methodologies of analysis: static headspace solid phase micro-extraction (HS-SPME) by gas chromatography-mass spectrometry (GC-MS) and inside needle dynamic extraction (INDEX) by MS-based electronic nose (MS-E-nose). RESULTS: Of the 137 volatiles compounds identified, most were found at significantly higher concentrations in SC3-5-1 than in PS in both seasons. These volatiles were mostly esters, alcohols, sulfur-derived esters and even some aldehydes and others. The number of variables with high correlation values was reduced by using correlation network analysis. Partial least squares-discriminant analysis (PLS-DA) achieved the correct classification of PS and SC3-5-1. The ions m/z 74, 91, 104, 105, 106 and 108, mainly volatile derivatives precursor phenylalanine, were the most discriminant in SC3-5-1 and PS. As many as 104 QTLs were mapped in season 1 and at least 78 QTLs in each season with an effect above the PS mean. CONCLUSION: GC-MS gave better discrimination than E-nose. Most of the QTLs that mapped in both seasons enhanced aroma volatiles associated with climacteric behaviour.


Asunto(s)
Cucurbitaceae/química , Frutas/química , Cromatografía de Gases y Espectrometría de Masas/métodos , Odorantes/análisis , Compuestos Orgánicos Volátiles/química , Cucurbitaceae/genética , Análisis de los Alimentos
4.
Cell Stress ; 7(8): 59-68, 2023 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-37664695

RESUMEN

Non-invasive imaging of tumors expressing reporter transgenes is a popular preclinical method for studying tumor development and response to therapy in vivo due to its ability to distinguish signal from tumors over background noise. However, the utilized transgenes, such as firefly luciferase, are immunogenic and, therefore, impact results when expressed in immune-competent hosts. This represents an important limitation, given that cancer immunology and immunotherapy are currently among the most impactful areas of research and therapeutic development. Here we present a non-immunogenic preclinical tumor imaging approach. Based on the expression of murine sodium iodide symporter (mNIS), it facilitates sensitive, non-invasive detection of syngeneic tumor cells in immune-competent tumor models without additional immunogenicity arising from exogenous transgenic protein or selection marker expression. NIS-expressing tumor cells internalize the gamma-emitting [99mTc]pertechnetate ion and so can be detected by SPECT (single photon emission computed tomography). Using a mouse model of pancreatic ductal adenocarcinoma hepatic metastases in immune-competent C57BL/6 mice, we demonstrate that the technique enables the detection of very early metastatic lesions and longitudinal assessment of immunotherapy responses using precise and quantifiable whole-body SPECT/CT imaging.

5.
J Gerontol A Biol Sci Med Sci ; 76(4): 601-610, 2021 03 31.
Artículo en Inglés | MEDLINE | ID: mdl-33053185

RESUMEN

Calorie restriction (CR) remains the most robust intervention to extend life span and improve healthspan. Though the cerebellum is more commonly associated with motor control, it has strong links with the hypothalamus and is thought to be associated with nutritional regulation and adiposity. Using a global mass spectrometry-based metabolomics approach, we identified 756 metabolites that were significantly differentially expressed in the cerebellar region of the brain of C57BL/6J mice, fed graded levels of CR (10, 20, 30, and 40 CR) compared to mice fed ad libitum for 12 hours a day. Pathway enrichment indicated changes in the pathways of adenosine and guanine (which are precursors of DNA production), aromatic amino acids (tyrosine, phenylalanine, and tryptophan) and the sulfur-containing amino acid methionine. We also saw increases in the tricarboxylic acid cycle (TCA) cycle, electron donor, and dopamine and histamine pathways. In particular, changes in l-histidine and homocarnosine correlated positively with the level of CR and food anticipatory activity and negatively with insulin and body temperature. Several metabolic and pathway changes acted against changes seen in age-associated neurodegenerative disorders, including increases in the TCA cycle and reduced l-proline. Carnitine metabolites contributed to discrimination between CR groups, which corroborates previous work in the liver and plasma. These results indicate the conservation of certain aspects of metabolism across tissues with CR. Moreover, this is the first study to indicate CR alters the cerebellar metabolome, and does so in a graded fashion, after only a short period of restriction.


Asunto(s)
Regulación del Apetito , Restricción Calórica/métodos , Cerebelo/fisiología , Envejecimiento Saludable/metabolismo , Hipotálamo/fisiología , Metaboloma/fisiología , Metabolómica/métodos , Transducción de Señal/fisiología , Animales , Hambre/fisiología , Longevidad , Espectrometría de Masas/métodos , Ratones , Ratones Endogámicos C57BL , Vías Nerviosas , Enfermedades Neurodegenerativas/metabolismo , Enfermedades Neurodegenerativas/prevención & control
6.
Rev Peru Med Exp Salud Publica ; 37(1): 142-147, 2020.
Artículo en Español | MEDLINE | ID: mdl-32520177

RESUMEN

This essay analyzes the contributions of the gender approach of feminist thinking to understand the relationship of women in pregnancy, childbirth, and postpartum with health service personnel. Origi nal qualitative design research was analyzed, were the relationship of women with health personnel is visualized. It is concluded that the gender approach of feminist thinking is a useful approximation to understand the problem of women's relations with health service personnel in aspects such as obstetric violence, care and the intersection of gender with other categories, in the framework of the health system.


Este ensayo analiza los aportes del enfoque de género del pensamiento feminista para comprender la relación de las mujeres en el embarazo, parto, y posparto con el personal de los servicios de salud. Se analizaron investigaciones originales de diseño cualitativo en las cuales se visualiza la relación de las mujeres con el personal de salud. Se concluye que el enfoque de género del pensamiento feminista es una aproximación útil para comprender la problemática de las relaciones de las mujeres con el personal de los servicios de salud en aspectos como la violencia obstétrica, el cuidado y la intersección del género con otras categorías, en el marco del sistema de salud.


Asunto(s)
Feminismo , Personal de Salud , Mujeres Embarazadas , Relaciones Profesional-Paciente , Femenino , Personal de Salud/psicología , Humanos , Parto , Periodo Posparto , Embarazo , Mujeres Embarazadas/psicología , Investigación Cualitativa
7.
Artículo en Español, Inglés | MEDLINE | ID: mdl-32520196

RESUMEN

OBJECTIVE: To understand the relationship established between women in a situation of pregnancy, childbirth and postpartum with the health services personnel according to social class in Bogotá (Colombia). MATERIALS AND METHODS: Qualitative study. Critical hermeneutical perspective and critical ethnography. Theoretical sampling. Analysis by triangulation in Atlas.ti. 9 women and 8 health professionals participated. 38 in-depth interviews were conducted for 13 months and 62 accompaniments to the maternal in the activities of prenatal control, vaccination, labor, postpartum consultation, follow up exams, prophylactic pisco course, hospitalization and waiting room, both in public services as private. RESULTS: There are inequalities according to social class in which the relationship between women and staff is configured in the following aspects: permeability to the needs of women, recognition of psychosocial aspects, having different points of view against a medical recommendation and right to complain or demand to improve. CONCLUSIONS: The situation described above intensifies gender issues in women with a less advantageous social class. It is necessary to develop interventions in educational and health institutions that consider aspects where human resources are sensitized on social issues related to the theoretical proposals of research and the democratization of medical information. It is unfair that the condition of social class and gender affects the quality of care and economically stratifies people's rights.


OBJETIVO: Comprender la relación que se establece entre las mujeres en situación de embarazo, parto y posparto con el personal de los servicios de salud según la clase social en Bogotá (Colombia). MATERIALES Y MÉTODOS: Estudio cualitativo, perspectiva hermenéutica crítica y etnografía crítica con muestreo teórico. Análisis por triangulación en Atlas.ti. Participaron nueve mujeres y ocho profesionales de la salud. Se realizaron 38 entrevistas a profundidad durante 13 meses y 62 acompañamientos a las mujeres en las actividades de control prenatal, vacunación, trabajo de parto, consulta posparto, exámenes de seguimiento, curso psicoprofiláctico, hospitalización y sala de espera, tanto en servicios públicos como privados. RESULTADOS: Existen desigualdades según la clase social en la forma en que se configura la relación entre las mujeres y el personal en los siguientes aspectos: permeabilidad a las necesidades de la mujer, reconocimiento de aspectos psicosociales, tener diferentes puntos de vista frente a una recomendación médica y derecho a quejarse o exigir para mejorar la atención de los servicios de salud. CONCLUSIONES: Lo anterior intensifica las problemáticas relacionadas con el género en las mujeres con una clase social menos aventajada. Es necesario el desarrollo de intervenciones en las instituciones educativas y de salud que tengan en cuenta aspectos donde se sensibilice el recurso humano en temas sociales relacionados con las propuestas teóricas de la investigación y la democratización de la información médica. Es injusto que la condición de clase social y de género afecte la calidad en la atención y estratifique económicamente los derechos de las personas.


Asunto(s)
Personal de Salud , Mujeres Embarazadas , Relaciones Profesional-Paciente , Clase Social , Colombia , Parto Obstétrico , Femenino , Personal de Salud/psicología , Humanos , Periodo Posparto , Embarazo , Mujeres Embarazadas/psicología , Investigación Cualitativa
8.
Mol Cancer Ther ; 19(9): 1809-1821, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32753387

RESUMEN

Despite significant progress in understanding the genetic landscape of T-cell acute lymphoblastic leukemia (T-ALL), the discovery of novel therapeutic targets has been difficult. Our results demonstrate that the levels of PIM1 protein kinase is elevated in early T-cell precursor ALL (ETP-ALL) but not in mature T-ALL primary samples. Small-molecule PIM inhibitor (PIMi) treatment decreases leukemia burden in ETP-ALL. However, treatment of animals carrying ETP-ALL with PIMi was not curative. To model other pathways that could be targeted to complement PIMi activity, HSB-2 cells, previously characterized as a PIMi-sensitive T-ALL cell line, were grown in increasing doses of PIMi. Gene set enrichment analysis of RNA sequencing data and functional enrichment of network modules demonstrated that the HOXA9, mTOR, MYC, NFκB, and PI3K-AKT pathways were activated in HSB-2 cells after long-term PIM inhibition. Reverse phase protein array-based pathway activation mapping demonstrated alterations in the mTOR, PI3K-AKT, and NFκB pathways, as well. PIMi-tolerant HSB-2 cells contained phosphorylated RelA-S536 consistent with activation of the NFκB pathway. The combination of NFκB and PIMis markedly reduced the proliferation in PIMi-resistant leukemic cells showing that this pathway plays an important role in driving the growth of T-ALL. Together these results demonstrate key pathways that are activated when HSB-2 cell line develop resistance to PIMi and suggest pathways that can be rationally targeted in combination with PIM kinases to inhibit T-ALL growth.


Asunto(s)
Resistencia a Antineoplásicos , Perfilación de la Expresión Génica/métodos , Redes Reguladoras de Genes/efectos de los fármacos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/administración & dosificación , Proteínas Proto-Oncogénicas c-pim-1/genética , Animales , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Proteínas de Homeodominio/genética , Humanos , Ratones , FN-kappa B/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Proto-Oncogénicas c-myc/genética , Proteínas Proto-Oncogénicas c-pim-1/antagonistas & inhibidores , Análisis de Secuencia de ARN , Transducción de Señal/efectos de los fármacos , Serina-Treonina Quinasas TOR/genética , Regulación hacia Arriba/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto
9.
Cell Chem Biol ; 26(8): 1110-1121.e4, 2019 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-31155510

RESUMEN

Increased telomerase activity is associated with malignancy and poor prognosis in human cancer, but the development of targeted agents has not yet provided clinical benefit. Here we report that, instead of targeting the telomerase enzyme directly, small molecules that bind to the G-hairpin of the hTERT G-quadruplex-forming sequence kill selectively malignant cells without altering the function of normal cells. RG260 targets the hTERT G-quadruplex stem-loop folding but not tetrad DNAs, leading to downregulation of hTERT expression. To improve physicochemical and pharmacokinetic properties, we derived a small-molecule analog, RG1603, from the parent compound. RG1603 induces mitochondrial defects including PGC1α and NRF2 inhibition and increases oxidative stress, followed by DNA damage and apoptosis. RG1603 injected as a single agent has tolerable toxicity while achieving strong anticancer efficacy in a tumor xenograft mouse model. These results demonstrate a unique approach to inhibiting the hTERT that functions by impairing mitochondrial activity, inducing cell death.


Asunto(s)
G-Cuádruplex/efectos de los fármacos , Bibliotecas de Moléculas Pequeñas/farmacología , Telomerasa/antagonistas & inhibidores , Animales , Apoptosis/efectos de los fármacos , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Humanos , Masculino , Ratones , Ratones SCID , Estructura Molecular , Bibliotecas de Moléculas Pequeñas/química , Relación Estructura-Actividad , Telomerasa/metabolismo
10.
Clin Cancer Res ; 25(3): 1036-1049, 2019 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-30327305

RESUMEN

PURPOSE: Adoptive T-cell therapy (ACT) of cancer, which involves the infusion of ex vivo-engineered tumor epitope reactive autologous T cells into the tumor-bearing host, is a potential treatment modality for cancer. However, the durable antitumor response following ACT is hampered either by loss of effector function or survival of the antitumor T cells. Therefore, strategies to improve the persistence and sustain the effector function of the antitumor T cells are of immense importance. Given the role of metabolism in determining the therapeutic efficacy of T cells, we hypothesize that inhibition of PIM kinases, a family of serine/threonine kinase that promote cell-cycle transition, cell growth, and regulate mTORC1 activity, can improve the potency of T cells in controlling tumor. EXPERIMENTAL DESIGN: The role of PIM kinases in T cells was studied either by genetic ablation (PIM1-/-PIM2-/-PIM3-/-) or its pharmacologic inhibition (pan-PIM kinase inhibitor, PimKi). Murine melanoma B16 was established subcutaneously and treated by transferring tumor epitope gp100-reactive T cells along with treatment regimen that involved inhibiting PIM kinases, anti-PD1 or both. RESULTS: With inhibition of PIM kinases, T cells had significant reduction in their uptake of glucose, and upregulated expression of memory-associated genes that inversely correlate with glycolysis. In addition, the expression of CD38, which negatively regulates the metabolic fitness of the T cells, was also reduced in PimKi-treated cells. Importantly, the efficacy of antitumor T-cell therapy was markedly improved by inhibiting PIM kinases in tumor-bearing mice receiving ACT, and further enhanced by adding anti-PD1 antibody to this combination. CONCLUSIONS: This study highlights the potential therapeutic significance of combinatorial strategies where ACT and inhibition of signaling kinase with checkpoint blockade could improve tumor control.


Asunto(s)
Compuestos de Bifenilo/farmacología , Inmunoterapia Adoptiva/métodos , Neoplasias Experimentales/terapia , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-pim-1/antagonistas & inhibidores , Linfocitos T/inmunología , Tiazolidinas/farmacología , Ensayos Antitumor por Modelo de Xenoinjerto/métodos , Animales , Anticuerpos/inmunología , Anticuerpos/farmacología , Línea Celular Tumoral , Humanos , Ratones Endogámicos C57BL , Ratones Noqueados , Neoplasias Experimentales/inmunología , Neoplasias Experimentales/metabolismo , Receptor de Muerte Celular Programada 1/inmunología , Receptor de Muerte Celular Programada 1/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Proto-Oncogénicas c-pim-1/genética , Proteínas Proto-Oncogénicas c-pim-1/metabolismo , Linfocitos T/metabolismo , Resultado del Tratamiento
11.
Reprod Biol Endocrinol ; 6: 14, 2008 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-18384674

RESUMEN

BACKGROUND: Neuropeptide Y (NPY), agouti related peptide (AgRP), cocaine and amphetamine-regulated transcript (CART) and melanocortins, the products of the proopiomelanocortin (POMC), are hypothalamic peptides involved in feeding regulation and energy homeostasis. Recent evidence has demonstrated their expression in rat and human placenta. METHODS: In the current study, we have investigated the expression of those neuropeptides in the rat placenta by real-time PCR using a model of maternal food restriction. RESULTS: Our results showed that placental-derived neuropeptides were regulated through pregnancy and following food restriction. CONCLUSION: These data could indicate that placental-derived neuropeptides represent a local regulatory circuit that may fine-tune control of energy balance during pregnancy.


Asunto(s)
Privación de Alimentos/fisiología , Regulación de la Expresión Génica/fisiología , Hipotálamo/metabolismo , Desnutrición/fisiopatología , Neuropéptidos/biosíntesis , Placenta/metabolismo , Preñez/fisiología , Ratas/fisiología , Proteína Relacionada con Agouti/biosíntesis , Proteína Relacionada con Agouti/genética , Animales , Femenino , Edad Gestacional , Desnutrición/genética , Melanocortinas/biosíntesis , Proteínas del Tejido Nervioso/biosíntesis , Proteínas del Tejido Nervioso/genética , Neuropéptido Y/biosíntesis , Neuropéptido Y/genética , Neuropéptidos/genética , Reacción en Cadena de la Polimerasa , Embarazo , Proopiomelanocortina/biosíntesis , Proopiomelanocortina/genética , ARN Mensajero/biosíntesis , Ratas Sprague-Dawley
12.
Regul Pept ; 146(1-3): 106-11, 2008 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-17928075

RESUMEN

Neuropeptide W (NPW) is a recently identified neuropeptide that binds to G-protein-coupled receptor 7 (GPR7) and 8 (GPR8). In rodent brain, NPW mRNA is confined to specific nuclei in hypothalamus, midbrain and brainstem. Expression of NPW mRNA has also been confirmed in peripheral organs such as stomach. Several reports suggested that brain NPW is implicated in the regulation of energy and hormonal homeostasis, namely the adrenal and thyroid axes; however the precise physiological role and regulation of peripheral NPW remains unclear. In this study, we examined the effects of nutritional status on the regulation of NPW in stomach mucosa. Our results show that in this tissue, NPW mRNA and protein expression is negatively regulated by fasting and food restriction, in all the models we studied: males, females and pregnant females. Next, we examined the effect of glucocorticoids and thyroid hormones on NPW mRNA expression in the stomach mucosa. Our data showed that NPW expression is decreased in this tissue after glucocorticoid treatment or hyperthyroidism. Conversely, hypothyroidism induces a marked increase in the expression of NPW in rat stomach. Overall, these data indicate that stomach NPW is regulated by nutritional and hormonal status.


Asunto(s)
Ayuno/fisiología , Mucosa Gástrica/efectos de los fármacos , Glucocorticoides/farmacología , Neuropéptidos/metabolismo , Estado Nutricional/fisiología , Hormonas Tiroideas/farmacología , Animales , Western Blotting , Regulación hacia Abajo/efectos de los fármacos , Mucosa Gástrica/metabolismo , Masculino , Neuropéptidos/genética , ARN Mensajero/biosíntesis , Ratas , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
13.
Work ; 61(3): 463-476, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30400123

RESUMEN

BACKGROUND: Due to improvements in breast cancer diagnosis and treatment, the healthcare system faces a growing number of cancer survivors. Breast cancer survivors experience many difficulties when returning to work, including discrimination at work and lack of support by employers and colleagues. OBJECTIVE: To point out the knowledge in literature up to date about return to work (RTW) after breast cancer, the factors influencing it and the interventions to facilitate it. METHODS: A literature search was conducted in January 2017 using the databases Medline (PubMed) and Scopus. Studies were included if they analyzed the problem of RTW in women treated for breast cancer. RESULTS: Twenty-six articles met the inclusion criteria. The studies were divided into four themes: factors facilitating or impeding RTW; interventions to enhance RTW; lived experiences of RTW; economic aspects related to cancer survivors and RTW. CONCLUSIONS: The heterogeneity of the interventions suggests the need for a better definition of the concept of RTW. To compare interventions, studies should use a rigorous approach and better outcome measures should be identified to evaluate RTW.


Asunto(s)
Neoplasias de la Mama/cirugía , Reinserción al Trabajo/psicología , Adulto , Neoplasias de la Mama/complicaciones , Femenino , Humanos , Persona de Mediana Edad , Rehabilitación Vocacional/normas , Reinserción al Trabajo/tendencias
14.
Mol Cancer Ther ; 17(12): 2710-2721, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30190422

RESUMEN

Cancer resistance to PI3K inhibitor therapy can be in part mediated by increases in the PIM1 kinase. However, the exact mechanism by which PIM kinase promotes tumor cell resistance is unknown. Our study unveils the pivotal control of redox signaling by PIM kinases as a driver of this resistance mechanism. PIM1 kinase functions to decrease cellular ROS levels by enhancing nuclear factor erythroid 2-related factor 2 (NRF2)/antioxidant response element activity. PIM prevents cell death induced by PI3K-AKT-inhibitory drugs through a noncanonical mechanism of NRF2 ubiquitination and degradation and translational control of NRF2 protein levels through modulation of eIF4B and mTORC1 activity. Importantly, PIM also controls NAD(P)H production by increasing glucose flux through the pentose phosphate shunt decreasing ROS production, and thereby diminishing the cytotoxicity of PI3K-AKT inhibitors. Treatment with PIM kinase inhibitors reverses this resistance phenotype, making tumors increasingly susceptible to small-molecule therapeutics, which block the PI3K-AKT pathway.


Asunto(s)
Resistencia a Antineoplásicos , Inhibidores de las Quinasa Fosfoinosítidos-3 , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Proto-Oncogénicas c-pim-1/metabolismo , Animales , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Sinergismo Farmacológico , Glutatión/metabolismo , Humanos , Masculino , Ratones SCID , Factor 2 Relacionado con NF-E2/metabolismo , Oxidación-Reducción , Fosfatidilinositol 3-Quinasas/metabolismo , Estabilidad Proteica/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-akt/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Ubiquitinación/efectos de los fármacos , Regulación hacia Arriba/efectos de los fármacos
15.
Oncotarget ; 8(18): 30199-30216, 2017 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-28415816

RESUMEN

New approaches are needed for the treatment of patients with T-cell acute lymphoblastic leukemia (T-ALL) who fail to achieve remission with chemotherapy. Analysis of the effects of pan-PIM protein kinase inhibitors on human T-ALL cell lines demonstrated that the sensitive cell lines expressed higher PIM1 protein kinase levels, whereas T-ALL cell lines with NOTCH mutations tended to have lower levels of PIM1 kinase and were insensitive to these inhibitors. NOTCH-mutant cells selected for resistance to gamma secretase inhibitors developed elevated PIM1 kinase levels and increased sensitivity to PIM inhibitors. Gene profiling using a publically available T-ALL dataset demonstrated overexpression of PIM1 in the majority of early T-cell precursor (ETP)-ALLs and a small subset of non-ETP ALL. While the PIM inhibitors blocked growth, they also stimulated ERK and STAT5 phosphorylation, demonstrating that activation of additional signaling pathways occurs with PIM inhibitor treatment. To block these pathways, Ponatinib, a broadly active tyrosine kinase inhibitor (TKI) used to treat chronic myelogenous leukemia, was added to this PIM-inhibitor regimen. The combination of Ponatinib with a PIM inhibitor resulted in synergistic T-ALL growth inhibition and marked apoptotic cell death. Treatment of mice engrafted with human T-ALL with these two agents significantly decreased the tumor burden and improved the survival of treated mice. This dual therapy has the potential to be developed as a novel approach to treat T-ALL with high PIM expression.


Asunto(s)
Antineoplásicos/farmacología , Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Proto-Oncogénicas c-pim-1/antagonistas & inhibidores , Secretasas de la Proteína Precursora del Amiloide/antagonistas & inhibidores , Animales , Antineoplásicos/uso terapéutico , Biomarcadores , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Resistencia a Antineoplásicos/genética , Sinergismo Farmacológico , Quimioterapia Combinada , Femenino , Perfilación de la Expresión Génica , Humanos , Ratones , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/mortalidad , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteómica , Proteínas Proto-Oncogénicas c-pim-1/genética , Proteínas Proto-Oncogénicas c-pim-1/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto
16.
Oncotarget ; 7(15): 20152-65, 2016 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-26956053

RESUMEN

The Pim family of serine/threonine protein kinases (Pim 1, 2, and 3) contribute to cellular transformation by regulating glucose metabolism, protein synthesis, and mitochondrial oxidative phosphorylation. Drugs targeting the Pim protein kinases are being tested in phase I/II clinical trials for the treatment of hematopoietic malignancies. The goal of these studies was to identify Pim substrate(s) that could help define the pathway regulated by these enzymes and potentially serve as a biomarker of Pim activity. To identify novel substrates, bioinformatics analysis was carried out to identify proteins containing a consensus Pim phosphorylation site. This analysis identified the insulin receptor substrate 1 and 2 (IRS1/2) as potential Pim substrates. Experiments were carried out in tissue culture, animals, and human samples from phase I trials to validate this observation and define the biologic readout of this phosphorylation. Our study demonstrates in both malignant and normal cells using either genetic or pharmacological inhibition of the Pim kinases or overexpression of this family of enzymes that human IRS1S1101 and IRS2S1149 are Pim substrates. In xenograft tumor experiments and in a human phase I clinical trial, a pan-Pim inhibitor administered in vivo to animals or humans decreased IRS1S1101 phosphorylation in tumor tissues. This phosphorylation was shown to have effects on the half-life of the IRS family of proteins, suggesting a role in insulin or IGF signaling. These results demonstrate that IRS1S1101 is a novel substrate for the Pim kinases and provide a novel marker for evaluation of Pim inhibitor therapy.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Compuestos de Bifenilo/uso terapéutico , Proteínas Sustrato del Receptor de Insulina/metabolismo , Leucemia Experimental/patología , Leucemia de Células T/patología , Proteínas Proto-Oncogénicas c-pim-1/metabolismo , Tiazolidinas/uso terapéutico , Animales , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Ensayos Clínicos Fase I como Asunto , Humanos , Leucemia Experimental/tratamiento farmacológico , Leucemia Experimental/metabolismo , Leucemia de Células T/tratamiento farmacológico , Leucemia de Células T/metabolismo , Masculino , Ratones , Ratones Endogámicos NOD , Ratones SCID , Estadificación de Neoplasias , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Neoplasias/patología , Fosforilación/efectos de los fármacos , Pronóstico , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Proto-Oncogénicas c-pim-1/antagonistas & inhibidores , Transducción de Señal/efectos de los fármacos , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto
17.
Rev. peru. med. exp. salud publica ; 37(1): 7-16, ene.-mar. 2020. tab, graf
Artículo en Español | LILACS | ID: biblio-1101790

RESUMEN

RESUMEN Objetivo: Comprender la relación que se establece entre las mujeres en situación de embarazo, parto y posparto con el personal de los servicios de salud según la clase social en Bogotá (Colombia). Materiales y métodos: Estudio cualitativo, perspectiva hermenéutica crítica y etnografía crítica con muestreo teórico. Análisis por triangulación en Atlas.ti. Participaron nueve mujeres y ocho profesionales de la salud. Se realizaron 38 entrevistas a profundidad durante 13 meses y 62 acompañamientos a las mujeres en las actividades de control prenatal, vacunación, trabajo de parto, consulta posparto, exámenes de seguimiento, curso psicoprofiláctico, hospitalización y sala de espera, tanto en servicios públicos como privados. Resultados: Existen desigualdades según la clase social en la forma en que se configura la relación entre las mujeres y el personal en los siguientes aspectos: permeabilidad a las necesidades de la mujer, reconocimiento de aspectos psicosociales, tener diferentes puntos de vista frente a una recomendación médica y derecho a quejarse o exigir para mejorar la atención de los servicios de salud. Conclusiones: Lo anterior intensifica las problemáticas relacionadas con el género en las mujeres con una clase social menos aventajada. Es necesario el desarrollo de intervenciones en las instituciones educativas y de salud que tengan en cuenta aspectos donde se sensibilice el recurso humano en temas sociales relacionados con las propuestas teóricas de la investigación y la democratización de la información médica. Es injusto que la condición de clase social y de género afecte la calidad en la atención y estratifique económicamente los derechos de las personas.


ABSTRACT Objective: To understand the relationship established between women in a situation of pregnancy, childbirth and postpartum with the health services personnel according to social class in Bogotá (Colombia). Materials and methods: Qualitative study. Critical hermeneutical perspective and critical ethnography. Theoretical sampling. Analysis by triangulation in Atlas.ti. 9 women and 8 health professionals participated. 38 in-depth interviews were conducted for 13 months and 62 accompaniments to the maternal in the activities of prenatal control, vaccination, labor, postpartum consultation, follow up exams, prophylactic pisco course, hospitalization and waiting room, both in public services as private. Results: There are inequalities according to social class in which the relationship between women and staff is configured in the following aspects: permeability to the needs of women, recognition of psychosocial aspects, having different points of view against a medical recommendation and right to complain or demand to improve. Conclusions: The situation described above intensifies gender issues in women with a less advantageous social class. It is necessary to develop interventions in educational and health institutions that consider aspects where human resources are sensitized on social issues related to the theoretical proposals of research and the democratization of medical information. It is unfair that the condition of social class and gender affects the quality of care and economically stratifies people's rights.


Asunto(s)
Femenino , Humanos , Embarazo , Relaciones Profesional-Paciente , Clase Social , Personal de Salud , Mujeres Embarazadas , Personal de Salud/psicología , Colombia , Parto Obstétrico , Investigación Cualitativa , Mujeres Embarazadas/psicología , Periodo Posparto
18.
Rev. peru. med. exp. salud publica ; 37(1): 142-147, ene.-mar. 2020.
Artículo en Español | LILACS | ID: biblio-1101793

RESUMEN

RESUMEN Este ensayo analiza los aportes del enfoque de género del pensamiento feminista para comprender la relación de las mujeres en el embarazo, parto, y posparto con el personal de los servicios de salud. Se analizaron investigaciones originales de diseño cualitativo en las cuales se visualiza la relación de las mujeres con el personal de salud. Se concluye que el enfoque de género del pensamiento feminista es una aproximación útil para comprender la problemática de las relaciones de las mujeres con el personal de los servicios de salud en aspectos como la violencia obstétrica, el cuidado y la intersección del género con otras categorías, en el marco del sistema de salud.


ABSTRACT This essay analyzes the contributions of the gender approach of feminist thinking to understand the relationship of women in pregnancy, childbirth, and postpartum with health service personnel. Origi nal qualitative design research was analyzed, were the relationship of women with health personnel is visualized. It is concluded that the gender approach of feminist thinking is a useful approximation to understand the problem of women's relations with health service personnel in aspects such as obstetric violence, care and the intersection of gender with other categories, in the framework of the health system.


Asunto(s)
Femenino , Humanos , Embarazo , Relaciones Profesional-Paciente , Personal de Salud , Feminismo , Mujeres Embarazadas , Personal de Salud/psicología , Parto , Investigación Cualitativa , Mujeres Embarazadas/psicología , Periodo Posparto
19.
Rev. Univ. Ind. Santander, Salud ; 52(3): 285-294, Julio 8, 2020. tab, graf
Artículo en Español | LILACS | ID: biblio-1155627

RESUMEN

Resumen Objetivo: comprender el acceso que tienen las mujeres en situación de embarazo, parto y post parto a los servicios de salud según la clase social en Bogotá (Colombia). Métodos: estudio cualitativo. Perspectiva hermenéutica crítica. Método etnografía crítica. Muestreo teórico. Análisis por triangulación en Atlas Ti. Participaron 9 mujeres y 8 profesionales de la salud. Se realizaron 38 entrevistas a profundidad durante 13 meses y 62 acompañamientos a las maternas en las actividades de control prenatal, vacunación, trabajo de parto, consulta post parto, exámenes de seguimiento, curso Psicoprofiláctico, hospitalización y sala de espera, tanto en servicios públicos como privados. Resultados: existen desigualdades según la clase social en el acceso que tienen las mujeres a los servicios de salud en los siguientes aspectos: acceso a servicio a especialistas, hacer la fila para esperar la atención, la disponibilidad de citas y agenda para programar la cita, perder la cita habiendo llegado al servicio, la prioridad que le dan las instituciones a las maternas, madrugar para conseguir atención, pedir la cita, las condiciones de la espera y elegir la clínica o el personal. Conclusiones: los anteriores aspectos se intensifican en clases sociales con menos ventajas. Se requiere disminuir las desigualdades sociales para disminuir las inequidades en salud.


Abstract Objective: to understand the access that women in pregnancy, childbirth and postpartum have to health services according to social class in Bogotá (Colombia). Methods: qualitative study. Critical hermeneutical perspective. Critical ethnography method. Theoretical sampling. Analysis by triangulation in Atlas Ti. 9 women and 8 health professionals participated. 38 in-depth interviews were carried out during 13 months and 62 accompaniments to the maternal in the activities of prenatal control, vaccination, labor, postpartum consultation, follow-up examinations, Psychoprophylactic course, hospitalization and waiting room, both in public services as private. Results: there are inequalities according to social class in the access that women have to health services in the following aspects: access to specialist services, queuing to wait for care, availability of appointments and schedule to schedule the appointment, Missing the appointment having arrived at the service, the priority that institutions give to maternal mothers, getting up early to get care, requesting an appointment, waiting conditions and choosing the clinic or staff. Conclusions: the previous aspects are intensified in social classes with less advantages. Reducing social inequalities is required to decrease health inequities.


Asunto(s)
Humanos , Femenino , Clase Social , Embarazo , Parto , Periodo Posparto , Accesibilidad a los Servicios de Salud , Salud Materno-Infantil , Derecho Sanitario , Servicios de Salud Materno-Infantil , Servicios de Salud Materna
20.
Front Nutr ; 1: 18, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25988120

RESUMEN

Hydroxytyrosol is one of the main phenolic components of olive oil. It is present in the fruit and leaf of the olive (Olea europaea L.). During the past decades, it has been well documented that this phenolic compound has health benefits and a protective action has been found in preclinical studies against several diseases. Here, we review its bioavailability in human beings and several assays showing significant results related with cardiovascular diseases, cancer, and acquired immunodeficiency syndrome (AIDS). Mechanisms of action include potent anti-oxidant and anti-inflammatory effects, among others. The importance of hydroxytyrosol in protection of low-density lipoproteins and consequently its implication in the reduction of cardiovascular disease risk has been highlighted by the European Food Safety Authority, concluding that 5 mg of hydroxytyrosol and its derivatives should be consumed daily to reach this effect at physiological level. We discuss the potential uses of this compound in supplements, nutraceutic foods, or topical formulations in the disease risk reduction. Finally, we conclude that more studies are needed to sustain or reject many other health claims not yet fully documented and to validate these newly available hydroxytyrosol-based products, because it seems to be a good candidate to reduce the risk of diseases mentioned.

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