Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 83
Filtrar
1.
Int J Mol Sci ; 23(23)2022 Nov 23.
Artículo en Inglés | MEDLINE | ID: mdl-36498952

RESUMEN

This study evaluated the mid-term (12-month) biomechanical, biocompatibility, and biological performance of additive-manufactured bioabsorbable iron-based interference screws (ISs). Two bioabsorbable iron IS types-manufactured using pure iron powder (iron_IS) and using pure iron powder with 0.2 wt% tricalcium phosphate (TCP_IS)-were compared with conventional metallic IS (control) using in vitro biocompatibility and degradation analyses and an in vivo animal study. The in vitro ultimate failure strength was significantly higher for iron_IS and TCP_IS than for control ISs at 3 months post-operatively; however, the difference between groups were nonsignificant thereafter. Moreover, at 3 months after implantation, iron_IS and TCP_IS increased bone volume fraction, bone surface area fraction, and percent intersection surface; the changes thereafter were nonsignificant. Iron_IS and TCP_IS demonstrated degradation over time with increased implant surface, decreased implant volume, and structure thickness; nevertheless, the analyses of visceral organs and biochemistry demonstrated normal results, except for time-dependent iron deposition in the spleen. Therefore, compared with conventional ISs, bioabsorbable iron-based ISs exhibit higher initial mechanical strength. Although iron-based ISs demonstrate high biocompatibility 12 months after implantation, their corrosive iron products may accumulate in the spleen. Because they demonstrate mechanical superiority along with considerable absorption capability after implantation, iron-based ISs may have potential applications in implantable medical-device development in the future.


Asunto(s)
Fosfatos de Calcio , Hierro , Animales , Conejos , Hierro/química , Porosidad , Implantes Absorbibles
3.
Materials (Basel) ; 15(10)2022 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-35629694

RESUMEN

Autogenous bone grafts are the gold standard for interbody fusion implant materials; however, they have several disadvantages. Tantalum (Ta) and titanium (Ti) are ideal materials for interbody cages because of their biocompatibility, particularly when they are incorporated into a three-dimensional (3D) porous structure. We conducted an in vitro investigation of the cell attachment and osteogenic markers of self-fabricated uniform porous Ti (20%, 40%, 60%, and 80%), nonporous Ti, and porous Ta cages (n = 6) in each group. Cell attachment, osteogenic markers, and alkaline phosphatase (ALP) were measured. An in vivo study was performed using a pig-posterior-instrumented anterior interbody fusion model to compare the porous Ti (60%), nonporous Ti, and porous Ta interbody cages in 12 pigs. Implant migration and subsidence, determined using plain radiographs, were recorded before surgery, immediately after surgery, and at 1, 3, and 6 months after surgery. Harvested implants were assessed for bone ingrowth and attachment. Relative to the 20% and 40% porous Ti cages, the 60% and 80% cages achieved superior cellular migration into cage pores. Among the cages, osteogenic marker and ALP activity levels were the highest in the 60% porous Ti cage, osteocalcin expression was the highest in the nonporous Ti cage, and the 60% porous Ti cage exhibited the lowest subsidence. In conclusion, the designed porous Ti cage is biocompatible and suitable for lumbar interbody fusion surgery and exhibits faster fusion with less subsidence compared with porous Ta and nonporous Ti cages.

4.
Materials (Basel) ; 15(8)2022 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-35454494

RESUMEN

Suture anchors are extensively used in rotator cuff tear surgery. With the advancement of three-dimensional printing technology, biodegradable metal has been developed for orthopedic applications. This study adopted three-dimensional-printed biodegradable Fe suture anchors with double-helical threads and commercialized non-vented screw-type Ti suture anchors with a tapered tip in the experimental and control groups, respectively. The in vitro study showed that the Fe and Ti suture anchors exhibited a similar ultimate failure load in 20-pound-per-cubic-foot polyurethane foam blocks and rabbit bone. In static immersion tests, the corrosion rate of Fe suture anchors was 0.049 ± 0.002 mm/year. The in vivo study was performed on New Zealand white rabbits and SAs were employed to reattach the ruptured supraspinatus tendon. The in vivo ultimate failure load of the Fe suture anchors was superior to that of the Ti suture anchors at 6 weeks. Micro-computed tomography showed that the bone volume fraction and bone surface density in the Fe suture anchors group 2 and 6 weeks after surgery were superior, and the histology confirmed that the increased bone volume around the anchor was attributable to mineralized osteocytes. The three-dimensional-printed Fe suture anchors outperformed the currently used Ti suture anchors.

5.
Cell Immunol ; 367: 104410, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34274730

RESUMEN

Rapid immune reconstitution without developing graft-versus-host disease (GVHD) is required for the success of allogeneic hematopoietic stem cell transplantation. Here, we analyzed the effects of pharmacological MEK inhibition on human polyclonal T-cell reconstitution in a humanized mouse GVHD model utilizing deep sequencing-based T-cell receptor (TCR) repertoire analysis. GVHD mice exhibited a skewed TCR repertoire with a common clone within target organs. The MEK inhibitor trametinib ameliorated GVHD and enabled engraftment of diverse T-cell clones. Furthermore, trametinib also ameliorated GVHD sparing diverse T cell repertoire, even when it was given from day 15 through 28. Although tacrolimus also reduced development of GVHD, it disturbed diverse T cell reconstitution and resulted in skewed TCR repertoire. Thus, trametinib not only suppresses GVHD-inducing T cells but also promotes human T cell reconstitution in vivo, providing a novel rationale for translational studies targeting human GVHD.


Asunto(s)
Enfermedad Injerto contra Huésped/prevención & control , Trasplante de Células Madre Hematopoyéticas , Inmunosupresores/uso terapéutico , Quinasas de Proteína Quinasa Activadas por Mitógenos/antagonistas & inhibidores , Inhibidores de Proteínas Quinasas/uso terapéutico , Piridonas/uso terapéutico , Pirimidinonas/uso terapéutico , Linfocitos T/inmunología , Animales , Células Cultivadas , Células Clonales , Enfermedad Injerto contra Huésped/inmunología , Humanos , Janus Quinasa 3/genética , Ratones , Ratones Noqueados , Ratones SCID , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Receptores de Antígenos de Linfocitos T/metabolismo , Tacrolimus/uso terapéutico , Trasplante Heterólogo
6.
Int J Mol Sci ; 22(14)2021 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-34298988

RESUMEN

This study evaluated the biocompatibility and biological performance of novel additive-manufactured bioabsorbable iron-based porous suture anchors (iron_SAs). Two types of bioabsorbable iron_SAs, with double- and triple-helical structures (iron_SA_2_helix and iron_SA_3_helix, respectively), were compared with the synthetic polymer-based bioabsorbable suture anchor (polymer_SAs). An in vitro mechanical test, MTT assay, and scanning electron microscope (SEM) analysis were performed. An in vivo animal study was also performed. The three types of suture anchors were randomly implanted in the outer cortex of the lateral femoral condyle. The ultimate in vitro pullout strength of the iron_SA_3_helix group was significantly higher than the iron_SA_2_helix and polymer_SA groups. The MTT assay findings demonstrated no significant cytotoxicity, and the SEM analysis showed cells attachment on implant surface. The ultimate failure load of the iron_SA_3_helix group was significantly higher than that of the polymer_SA group. The micro-CT analysis indicated the iron_SA_3_helix group showed a higher bone volume fraction (BV/TV) after surgery. Moreover, both iron SAs underwent degradation with time. Iron_SAs with triple-helical threads and a porous structure demonstrated better mechanical strength and high biocompatibility after short-term implantation. The combined advantages of the mechanical superiority of the iron metal and the possibility of absorption after implantation make the iron_SA a suitable candidate for further development.


Asunto(s)
Implantes Absorbibles , Materiales Biocompatibles , Anclas para Sutura , Alanina Transaminasa/sangre , Animales , Materiales Biocompatibles/química , Materiales Biocompatibles/toxicidad , Fenómenos Biomecánicos , Nitrógeno de la Urea Sanguínea , Fosfatos de Calcio/química , Fosfatos de Calcio/toxicidad , Sulfato de Calcio/administración & dosificación , Sulfato de Calcio/química , Sulfato de Calcio/toxicidad , Creatinina/sangre , Diseño de Equipo , Fémur/diagnóstico por imagen , Fémur/ultraestructura , Hierro , Rayos Láser , Ensayo de Materiales , Microscopía Electrónica de Rastreo , Estructura Molecular , Oseointegración , Polímeros/química , Polímeros/toxicidad , Porosidad , Conejos , Distribución Aleatoria , Resistencia a la Tracción , Vísceras , Microtomografía por Rayos X
7.
AJNR Am J Neuroradiol ; 42(5): 838-844, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33737268

RESUMEN

BACKGROUND AND PURPOSE: Differentiating glioblastoma from solitary brain metastasis preoperatively using conventional MR images is challenging. Deep learning models have shown promise in performing classification tasks. The diagnostic performance of a deep learning-based model in discriminating glioblastoma from solitary brain metastasis using preoperative conventional MR images was evaluated. MATERIALS AND METHODS: Records of 598 patients with histologically confirmed glioblastoma or solitary brain metastasis at our institution between February 2006 and December 2017 were retrospectively reviewed. Preoperative contrast-enhanced T1WI and T2WI were preprocessed and roughly segmented with rectangular regions of interest. A deep neural network was trained and validated using MR images from 498 patients. The MR images of the remaining 100 were used as an internal test set. An additional 143 patients from another tertiary hospital were used as an external test set. The classifications of ResNet-50 and 2 neuroradiologists were compared for their accuracy, precision, recall, F1 score, and area under the curve. RESULTS: The areas under the curve of ResNet-50 were 0.889 and 0.835 in the internal and external test sets, respectively. The area under the curve of neuroradiologists 1 and 2 were 0.889 and 0.768 in the internal test set and 0.857 and 0.708 in the external test set, respectively. CONCLUSIONS: A deep learning-based model may be a supportive tool for preoperative discrimination between glioblastoma and solitary brain metastasis using conventional MR images.


Asunto(s)
Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/secundario , Aprendizaje Profundo , Glioblastoma/diagnóstico por imagen , Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética/métodos , Adulto , Anciano , Área Bajo la Curva , Diagnóstico Diferencial , Femenino , Humanos , Aumento de la Imagen , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Estudios Retrospectivos
8.
Int J Mol Sci ; 21(10)2020 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-32455543

RESUMEN

The interference screw fixation method is used to secure a graft in the tibial tunnel during anterior cruciate ligament reconstruction surgery. However, several complications have been reported, such as biodegradable screw breakage, inflammatory or foreign body reaction, tunnel enlargement, and delayed graft healing. Using additive manufacturing (AM) technology, we developed a titanium alloy (Ti6Al4V) interference screw with chemically calcium phosphate surface modification technology to improve bone integration in the tibial tunnel. After chemical and heat treatment, the titanium screw formed a dense apatite layer on the metal surface in simulated body fluid. Twenty-seven New Zealand white rabbits were randomly divided into control and additive manufactured (AMD) screw groups. The long digital extensor tendon was detached and translated into a tibial plateau tunnel (diameter: 2.0 mm) and transfixed with an interference screw while the paw was in dorsiflexion. Biomechanical analyses, histological analyses, and an imaging study were performed at 1, 3, and 6 months. The biomechanical test showed that the ultimate pull-out load failure was significantly higher in the AMD screw group in all tested periods. Micro-computed tomography analyses revealed early woven bone formation in the AMD screw group at 1 and 3 months. In conclusion, AMD screws with bioactive surface modification improved bone ingrowth and enhanced biomechanical performance in a rabbit model.


Asunto(s)
Tornillos Óseos/normas , Oseointegración , Impresión Tridimensional , Tendones/cirugía , Tibia/cirugía , Aleaciones/química , Animales , Tornillos Óseos/efectos adversos , Interfase Hueso-Implante/cirugía , Fosfatos de Calcio/química , Porosidad , Conejos
9.
Int J Hematol ; 109(2): 221-227, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30368656

RESUMEN

Adult T-cell leukemia (ATL) is an aggressive mature T-cell malignancy with a poor prognosis. The anti-C-C motif chemokine receptor 4 (CCR4) antibody mogamulizumab (moga) reduces ATL cells and induces reconstitution of polyclonal T cells; however, ATL cases often remain resistant and moga sometimes causes fatal immunopathology. Epstein-Barr virus (EBV)-related B-cell lymphoma develops in severely immunocompromised subjects, and is particularly associated with impaired T-cell immunity. Here, we report an ATL patient who had received conventional chemotherapy plus moga, and subsequently developed EBV-related diffuse large B-cell lymphoma (DLBCL) of the central nervous system. Next-generation sequencing-based T-cell receptor repertoire analyses identified residual abnormal clones and revealed that reconstitution of polyclonal T cells was incomplete, even after moga treatment. Furthermore, a skin rash that developed after moga treatment was found to contain ATL clones. This case suggests that the limited therapeutic effects of moga and incomplete T-cell reconstitution are associated with severely impaired T-cell immunity and subsequent development of EBV-related DLBCL.


Asunto(s)
Herpesvirus Humano 4 , Linfoma de Células B Grandes Difuso/etiología , Adulto , Anticuerpos Monoclonales Humanizados/uso terapéutico , Neoplasias del Sistema Nervioso Central , Niño , Células Clonales/patología , Humanos , Leucemia-Linfoma de Células T del Adulto/complicaciones , Leucemia-Linfoma de Células T del Adulto/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/virología , Linfocitos T/inmunología , Linfocitos T/patología
10.
Molecules ; 23(5)2018 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-29710774

RESUMEN

The synthesis and anti-inflammatory effects of certain pyrazolo[4,3-c]quinoline derivatives 2a⁻2r are described. The anti-inflammatory activities of these derivatives were evaluated by means of inhibiting nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Among them, 3-amino-4-(4-hydroxyphenylamino)-1H-pyrazolo[4,3-c]-quinoline (2i) and 4-(3-amino-1H-pyrazolo[4,3-c]quinolin-4-ylamino)benzoic acid (2m) exhibited significant inhibition of LPS-stimulated NO production with a potency approximately equal to that of the positive control, 1400 W. Important structure features were analyzed by quantitative structure⁻activity relationship (QSAR) analysis to give better insights into the structure determinants for predicting the inhibitory effects on the accumulation of nitric oxide for RAW 264.7 cells in response to LPS. In addition, our results indicated that their anti-inflammatory effects involve the inhibition of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) protein expression. Further studies on the structural optimization are ongoing.


Asunto(s)
Antiinflamatorios/síntesis química , Macrófagos/citología , Pirazoles/síntesis química , Quinolinas/síntesis química , Animales , Antiinflamatorios/química , Antiinflamatorios/farmacología , Ciclooxigenasa 2/química , Ciclooxigenasa 2/metabolismo , Regulación hacia Abajo , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Lipopolisacáridos/efectos adversos , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones , Modelos Moleculares , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/química , Óxido Nítrico Sintasa de Tipo II/metabolismo , Pirazoles/química , Pirazoles/farmacología , Relación Estructura-Actividad Cuantitativa , Quinolinas/química , Quinolinas/farmacología , Células RAW 264.7
11.
Front Immunol ; 9: 668, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29666626

RESUMEN

The human immune system is a fine network consisted of the innumerable numbers of functional cells that balance the immunity and tolerance against various endogenous and environmental challenges. Although advances in modern immunology have revealed a role of many unique immune cell subsets, technologies that enable us to capture the whole landscape of immune responses against specific antigens have been not available to date. Acquired immunity against various microorganisms including host microbiome is principally founded on T cell and B cell populations, each of which expresses antigen-specific receptors that define a unique clonotype. Over the past several years, high-throughput next-generation sequencing has been developed as a powerful tool to profile T- and B-cell receptor repertoires in a given individual at the single-cell level. Sophisticated immuno-bioinformatic analyses by use of this innovative methodology have been already implemented in clinical development of antibody engineering, vaccine design, and cellular immunotherapy. In this article, we aim to discuss the possible application of high-throughput immune receptor sequencing in the field of nutritional and intestinal immunology. Although there are still unsolved caveats, this emerging technology combined with single-cell transcriptomics/proteomics provides a critical tool to unveil the previously unrecognized principle of host-microbiome immune homeostasis. Accumulation of such knowledge will lead to the development of effective ways for personalized immune modulation through deeper understanding of the mechanisms by which the intestinal environment affects our immune ecosystem.


Asunto(s)
Microbioma Gastrointestinal/inmunología , Secuenciación de Nucleótidos de Alto Rendimiento , Inmunidad Adaptativa , Animales , Homeostasis , Humanos
12.
Oncoimmunology ; 7(3): e1405204, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29399406

RESUMEN

Although the anti-CCR4 antibody mogamulizumab (moga) shows striking antitumor activity against adult T cell leukemia (ATL), it can also cause fatal immunological pathology such as severe skin rash and graft-versus-host disease, which might be attributed to depletion of CCR4+ regulatory T cells. We previously showed that next generation sequencing enables precise analysis of the T cell receptor (TCR) repertoire, and we here used the technique to reveal the immunological dynamics in moga-treated ATL patients. Treatment with moga resulted in remarkable reduction or elimination of clonal cells, and enhanced reconstitution of non-tumor polyclonal CD4+ T cells and oligoclonal CD8+ T cells. Interestingly, cutaneous T cells infiltrating moga-related skin rashes did not share the same major clones in peripheral blood, which minimizes the possibility of cross-reaction. Thus, deep sequencing of the TCR can reveal the immune reconstitution of moga-treated ATL and provides powerful insights into its mode of action.

13.
Curr Oncol ; 25(6): e507-e515, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30607117

RESUMEN

Background: Reducing inflammatory factors in wound exudate is a promising treatment approach for healing wounds in postsurgical breast cancer patients. Traditional Chinese Medicine (tcm) treatments have been shown to be beneficial and safe for optimal regulation of oxidative stress during the postoperative period. In the present clinical trial, we evaluated the effectiveness of a promising Chinese herbal formula, San Huang decoction [shd (Radix astragali, Radix et rhizoma rhei, and Rhizoma curcuma longa, 3:1:1; supplemental Table 1)], on wound inflammatory response after mastectomy. Methods: The study randomized 30 patients with breast cancer who fulfilled the inclusion and exclusion criteria to either a treatment (n = 15) or a control group (n = 15). Patients in the treatment group received liquid shd, taken twice daily with or without food. Treatment was given for 1 day before surgery and for 7 days postoperatively. Participants in the control group received a placebo on the same schedule as the treatment group. Outcomes measured in every subject included clinical tcm and wound inflammation symptom scores, daily and total amounts of drainage fluid, and levels of inflammatory factors in the exudate [tumour necrosis factor α (tnf-α), interleukins 6 (il-6), 8 (il-8), and 2R (il-2R), human C-reactive protein (crp)] at 2 hours and on days 1, 3, and 7 postoperatively. Results: The total amount of drainage fluid over 7 days was significantly lower in the treatment group (572.20 ± 93.95 mL) than in the control group (700.40 ± 107.38 mL). The tcm symptom score was also lower in treatment group (day 7: 1.87 ± 0.83 vs. 4.80 ± 3.61, p = 0.049), as was the inflammatory symptom score (day 7: 0.67 ± 0.72 vs. 3.67 ± 2.50, p = 0.001). Levels of tnf-α, il-6, il-8, il-2R, and crp in drainage fluid were significantly lower with shd treatment. Conclusions: Perioperative treatment with shd effectively lessened postoperative exudate and ameliorated inflammatory symptoms in patients who underwent surgery for breast cancer.


Asunto(s)
Neoplasias de la Mama/complicaciones , Medicamentos Herbarios Chinos/uso terapéutico , Exudados y Transudados/efectos de los fármacos , Inflamación/tratamiento farmacológico , Inflamación/etiología , Complicaciones Posoperatorias/tratamiento farmacológico , Complicaciones Posoperatorias/etiología , Adulto , Anciano , Antiinflamatorios/administración & dosificación , Antiinflamatorios/uso terapéutico , Biomarcadores , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/cirugía , Estudios de Casos y Controles , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/efectos adversos , Femenino , Humanos , Mastectomía/efectos adversos , Mastectomía/métodos , Medicina Tradicional China , Persona de Mediana Edad , Resultado del Tratamiento
14.
Aliment Pharmacol Ther ; 46(8): 758-767, 2017 10.
Artículo en Inglés | MEDLINE | ID: mdl-28799258

RESUMEN

BACKGROUND: Patients who have undergone endoscopic resection of early gastric cancers (EGCs) are at risk for metachronous gastric neoplasm. AIM: To determine whether serum level of pepsinogen (PG), a marker of gastric atrophy, can determine which patients who have undergone endoscopic submucosal dissection for EGC are at risk for metachronous gastric neoplasm. We also investigated the effects of Helicobacter pylori eradication on metachronous gastric neoplasm incidence. METHODS: We performed a retrospective study of 590 consecutive patients who underwent endoscopic submucosal dissection for EGC, from January 2008 to May 2013 at a tertiary centre in South Korea; serum levels of PG were measured at the time of endoscopic submucosal dissection and H. pylori infection status were recorded. In case of proven presence of current H. pylori infection, eradication treatment was provided. Patients underwent follow-up endoscopies at 3 months, 9 months, and each year after the procedure to detect neoplasms and were tested for H. pylori infection; serum levels of PG were measured at these time points from 442 of the patients. The main and sub-cohorts were assessed for baseline characteristics, H. pylori infection, serum level of PG, and metachronous gastric neoplasm lesions. RESULTS: During a median follow-up period of 47.7 months, 64 patients developed metachronous gastric neoplasms. In multivariate analysis of the main cohort (n = 590), risk factors for metachronous gastric neoplasm included persistent H. pylori infection (hazard ratio [HR], 2.532; P = .022) and serum ratio of PGI:PGII of three or less at the time of endoscopic submucosal dissection (HR, 1.881; P = .018). Among patients with serum PG measurements, persistent H. pylori infection (odds ratio [OR], 4.404; P = .009) and persistent decrease in mean serum ratio of PGI:PGII to 3 or less were associated with increased risk of metachronous gastric neoplasm (OR, 2.141; P = .039). CONCLUSIONS: In a retrospective analysis of patients who underwent endoscopic resection of EGCs, eradication of H. pylori infection reduced risk for metachronous gastric neoplasm. Serum ratio of PGI:PGII of 3 or less also increase risk of metachronous gastric neoplasm after endoscopic submucosal dissection. ClinicalTrials.gov. registry number, NCT02682446.


Asunto(s)
Resección Endoscópica de la Mucosa/métodos , Infecciones por Helicobacter/epidemiología , Pepsinógeno A/sangre , Neoplasias Gástricas/epidemiología , Anciano , Resección Endoscópica de la Mucosa/efectos adversos , Femenino , Mucosa Gástrica/patología , Gastritis Atrófica/patología , Infecciones por Helicobacter/diagnóstico , Helicobacter pylori/aislamiento & purificación , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Neoplasias Primarias Secundarias/epidemiología , Modelos de Riesgos Proporcionales , República de Corea , Estudios Retrospectivos , Factores de Riesgo , Neoplasias Gástricas/patología
15.
Sci Rep ; 7: 45043, 2017 03 27.
Artículo en Inglés | MEDLINE | ID: mdl-28344335

RESUMEN

Influenza A virus (IAV) membrane proteins hemagglutinin (HA) and neuraminidase (NA) are determinants of virus infectivity, transmissibility, pathogenicity, host specificity, and major antigenicity. HA binds to a virus receptor, a sialoglycoprotein or sialoglycolipid, on the host cell and mediates virus attachment to the cell surface. The hydrolytic enzyme NA cleaves sialic acid from viral receptors and accelerates the release of progeny virus from host cells. In this study, we identified a novel function of HA and NA as machinery for viral motility. HAs exchanged binding partner receptors iteratively, generating virus movement on a receptor-coated glass surface instead of a cell surface. The virus movement was also dependent on NA. Virus movement mediated by HA and NA resulted in a three to four-fold increase in virus internalisation by cultured cells. We concluded that cooperation of HA and NA moves IAV particles on a cell surface and enhances virus infection of host cells.


Asunto(s)
Glicoproteínas Hemaglutininas del Virus de la Influenza/metabolismo , Movimiento , Neuraminidasa/metabolismo , Internalización del Virus , Animales , Línea Celular Tumoral , Perros , Células HEK293 , Humanos , Virus de la Influenza A/metabolismo , Virus de la Influenza A/fisiología , Células de Riñón Canino Madin Darby , Receptores Virales/metabolismo
16.
Cancer Immunol Res ; 4(8): 644-9, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-27215229

RESUMEN

The regulatory T cells (Treg) with the most potent immunosuppressive activity are the effector Tregs (eTreg) with a CD45RA(-)Foxp3(++)CCR4(+) phenotype. Adult T-cell leukemia (ATL) cells often share the Treg phenotype and also express CCR4. Although mogamulizumab, a monoclonal antibody to CCR4, shows marked antitumor effects against ATL and peripheral T-cell lymphoma, concerns have been raised that it may induce severe autoimmune immunopathology by depleting eTregs. Here, we present case reports for two patients with ATL who responded to mogamulizumab but developed a severe skin rash and autoimmune brainstem encephalitis. Deep sequencing of the T-cell receptor revealed that ATL cells and naturally occurring Tregs within the cell population with a Treg phenotype can be clearly distinguished according to CADM1 expression. The onset of skin rash and brainstem encephalitis was coincident with eTreg depletion from the peripheral blood, whereas ATL relapses were coincident with eTreg recovery. These results imply that eTreg numbers in the peripheral blood sensitively reflect the equilibrium between antitumor immunity and autoimmunity, and that mogamulizumab might suppress ATL until the eTreg population recovers. Close monitoring of eTreg numbers is crucial if we are to provide immunomodulatory treatments that target malignancy without severe adverse events. Cancer Immunol Res; 4(8); 644-9. ©2016 AACR.


Asunto(s)
Autoinmunidad , Inmunidad , Leucemia-Linfoma de Células T del Adulto/inmunología , Leucemia-Linfoma de Células T del Adulto/metabolismo , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo , Anciano , Biomarcadores , Biopsia , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Terapia Combinada , Humanos , Inmunofenotipificación , Leucemia-Linfoma de Células T del Adulto/diagnóstico , Leucemia-Linfoma de Células T del Adulto/terapia , Imagen por Resonancia Magnética , Masculino , Fenotipo , Piel/patología
17.
Radiat Prot Dosimetry ; 167(1-3): 316-20, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25948832

RESUMEN

Exposure to ionising radiation induces male infertility, accompanied by increasing permeability of the blood-testis barrier. However, the effect on male fertility by low-dose-rate chronic radiation has not been investigated. In this study, the effects of low-dose-rate chronic radiation on male mice were investigated by measuring the levels of tight-junction-associated proteins (ZO-1 and occludin-1), Niemann-Pick disease type 2 protein (NPC-2) and antisperm antibody (AsAb) in serum. BALB/c mice were exposed to low-dose-rate radiation (3.49 mGy h(-1)) for total exposures of 0.02 (6 h), 0.17 (2 d) and 1.7 Gy (21 d). Based on histological examination, the diameter and epithelial depth of seminiferous tubules were significantly decreased in 1.7-Gy-irradiated mice. Compared with those of the non-irradiated group, 1.7-Gy-irradiated mice showed significantly decreased ZO-1, occludin-1 and NPC-2 protein levels, accompanied with increased serum AsAb levels. These results suggest potential blood-testis barrier injury and immune infertility in male mice exposed to low-dose-rate chronic radiation.


Asunto(s)
Barrera Hematotesticular/lesiones , Barrera Hematotesticular/efectos de la radiación , Infertilidad Masculina/inmunología , Exposición a la Radiación/efectos adversos , Traumatismos Experimentales por Radiación/inmunología , Testículo/efectos de la radiación , Animales , Barrera Hematotesticular/inmunología , Relación Dosis-Respuesta en la Radiación , Infertilidad Masculina/etiología , Infertilidad Masculina/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Dosis de Radiación , Traumatismos por Radiación , Traumatismos Experimentales por Radiación/etiología , Traumatismos Experimentales por Radiación/patología
18.
Oncogene ; 34(50): 6055-65, 2015 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-25746001

RESUMEN

Extracellular Matrix Protein 1 (ECM1) is a marker for tumorigenesis and is correlated with invasiveness and poor prognosis in various types of cancer. However, the functional role of ECM1 in cancer metastasis is unclear. Here, we detected high ECM1 level in breast cancer patient sera that was associated with recurrence of tumor. The modulation of ECM1 expression affected not only cell migration and invasion, but also sphere-forming ability and drug resistance in breast cancer cell lines. In addition, ECM1 regulated the gene expression associated with the epithelial to mesenchymal transition (EMT) progression and cancer stem cell (CSC) maintenance. Interestingly, ECM1 increased ß-catenin expression at the post-translational level through induction of MUC1, which was physically associated with ß-catenin. Indeed, the association between ß-catenin and the MUC1 cytoplasmic tail was increased by ECM1. Furthermore, forced expression of ß-catenin altered the gene expression that potentiated EMT progression and CSC phenotype maintenance in the cells. These data provide evidence that ECM1 has an important role in cancer metastasis through ß-catenin stabilization.


Asunto(s)
Proteínas de la Matriz Extracelular/fisiología , beta Catenina/fisiología , Línea Celular Tumoral , Movimiento Celular , Resistencia a Antineoplásicos , Transición Epitelial-Mesenquimal , Femenino , Humanos , Mucina-1/fisiología , Invasividad Neoplásica , Metástasis de la Neoplasia , Células Madre Neoplásicas , Estabilidad Proteica , beta Catenina/genética
19.
Cell Death Differ ; 22(4): 665-76, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25342465

RESUMEN

Cytokeratin19 (KRT19) is widely used as a biomarker for the detection of disseminated tumors. Using an LC-MS/MS proteomics approach, we found that KRT19 was upregulated in HER2-overexpressing cells and tissues. KRT19 expression was induced by HER2-downstream ERK at the transcriptional level. Another HER2-downstream kinase, Akt, was found to phosphorylate KRT19 on Ser35 and induce membrane translocation of KRT19 and remodeling of KRT19 from filamentous to granulous form. KRT19 phosphorylated by Akt could bind HER2 on the plasma membrane and stabilized HER2 via inhibition of proteasome-mediated degradation of HER2. Silencing of KRT19 by shRNA resulted in increased ubiquitination and destabilization of HER2. Moreover, treatment of KRT19 antibody resulted in downregulation of HER2 and reduced cell viability. These data provide a new rationale for targeting HER2-positive breast cancers.


Asunto(s)
Membrana Celular/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Queratina-19/metabolismo , Receptor ErbB-2/metabolismo , Animales , Anticuerpos/inmunología , Anticuerpos/farmacología , Anticuerpos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Quinasas MAP Reguladas por Señal Extracelular/antagonistas & inhibidores , Femenino , Regulación de la Expresión Génica , Células HEK293 , Humanos , Queratina-19/antagonistas & inhibidores , Queratina-19/inmunología , Sistema de Señalización de MAP Quinasas , Células MCF-7 , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Ratones Transgénicos , Unión Proteica , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptor ErbB-2/química , Transcripción Genética/efectos de los fármacos
20.
Hum Exp Toxicol ; 34(3): 227-39, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24972622

RESUMEN

This study investigated the gastroprotective effects of diallyl disulfide (DADS), a secondary organosulfur compound derived from garlic (Allium sativum L.) on experimental model of ethanol (EtOH)-induced gastric ulcer in rats. The antiulcerogenic activity of DADS was evaluated by gross/histopathological inspection, pro-inflammatory cytokines, and lipid peroxidation with antioxidant enzyme activities in the stomach. DADS (100 mg/kg) was administered by oral gavage 2 h prior to EtOH treatment (5 ml/kg). The animals were killed 1 h after receiving EtOH treatment. Pretreatment with DADS attenuated EtOH-induced gastric mucosal injury, as evidenced by decreased severity of hemorrhagic lesions and gastric ulcer index upon visual inspection. DADS also prevented histopathological alterations and gastric apoptotic changes caused by EtOH. An increase in tumor necrosis factor-α (TNF-α) and inducible nitric oxide synthase was observed in the gastric tissues of EtOH-treated rats that coincided with increased serum TNF-α and interleukin 6 levels. In contrast, DADS effectively suppressed production of pro-inflammatory mediators induced by EtOH. Furthermore, DADS prevented the formation of gastric malondialdehyde and the depletion of reduced glutathione content and restored antioxidant enzyme activities, such as catalase, glutathione peroxidase, and glutathione reductase in the gastric tissues of EtOH-treated rats. These results indicate that DADS prevents gastric mucosal damage induced by acute EtOH administration in rats and that the protective effects of DADS may be due to its potent antioxidant and anti-inflammatory activities.


Asunto(s)
Compuestos Alílicos/uso terapéutico , Antiulcerosos/uso terapéutico , Disulfuros/uso terapéutico , Úlcera Gástrica/tratamiento farmacológico , Compuestos Alílicos/farmacología , Animales , Antiulcerosos/farmacología , Apoptosis/efectos de los fármacos , Catalasa/metabolismo , Disulfuros/farmacología , Etanol , Femenino , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patología , Glutatión/metabolismo , Glutatión Peroxidasa/metabolismo , Glutatión Reductasa/metabolismo , Interleucina-6/sangre , Interleucina-6/metabolismo , Óxido Nítrico Sintasa de Tipo II/sangre , Óxido Nítrico Sintasa de Tipo II/metabolismo , Ratas Sprague-Dawley , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patología , Factor de Necrosis Tumoral alfa/sangre , Factor de Necrosis Tumoral alfa/metabolismo
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA