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1.
Nat Commun ; 11(1): 525, 2020 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-31988276

RESUMEN

Liquid biopsies are providing new opportunities for detection of residual disease in cell-free DNA (cfDNA) after surgery but may be confounded through identification of alterations arising from clonal hematopoiesis. Here, we identify circulating tumor-derived DNA (ctDNA) alterations through ultrasensitive targeted sequencing analyses of matched cfDNA and white blood cells from the same patient. We apply this approach to analyze samples from patients in the CRITICS trial, a phase III randomized controlled study of perioperative treatment in patients with operable gastric cancer. After filtering alterations from matched white blood cells, the presence of ctDNA predicts recurrence when analyzed within nine weeks after preoperative treatment and after surgery in patients eligible for multimodal treatment. These analyses provide a facile method for distinguishing ctDNA from other cfDNA alterations and highlight the utility of ctDNA as a predictive biomarker of patient outcome to perioperative cancer therapy and surgical resection in patients with gastric cancer.


Asunto(s)
Ácidos Nucleicos Libres de Células/química , ADN de Neoplasias/análisis , Leucocitos/química , Recurrencia Local de Neoplasia/diagnóstico , Análisis de Secuencia de ADN , Neoplasias Gástricas/diagnóstico , ADN de Neoplasias/química , Hematopoyesis , Humanos , Pronóstico , Prueba de Estudio Conceptual , Ensayos Clínicos Controlados Aleatorios como Asunto , Neoplasias Gástricas/genética , Análisis de Supervivencia
2.
Chem Commun (Camb) ; 56(1): 74-77, 2020 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-31790117

RESUMEN

We developed a new method for the de novo formation of fluorophores based on citrate (DNFC) in biological samples. Use of an amide coupling reagent and microwave irradiation greatly facilitates the fluorophore formation on peptides and proteins with N-terminal cysteine or serine. Since N-terminal cysteine and serine can form thiazolopyridone- or oxazolopyridone-based fluorophores emitting blue and green fluorescence, respectively, by the DNFC staining, each organelle, cell and tissue exhibited a characteristic fluorescence distribution. The DNFC staining is able to provide a new potential protocol for future cell imaging, histology and diagnosis.


Asunto(s)
Colorantes Fluorescentes/metabolismo , Sondas Moleculares/metabolismo , Péptidos/metabolismo , Proteínas/metabolismo , Animales , Línea Celular Tumoral , Ácido Cítrico/metabolismo , Cisteína/química , Fluorescencia , Colorantes Fluorescentes/química , Células HEK293 , Humanos , Ratones , Microscopía Confocal/métodos , Microscopía Fluorescente/métodos , Sondas Moleculares/química , Células 3T3 NIH , Péptidos/química , Prueba de Estudio Conceptual , Proteínas/química , Piridonas/química , Piridonas/metabolismo , Serina/química , Tiazoles/química , Tiazoles/metabolismo
3.
Urology ; 135: 171-172, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31589882

RESUMEN

OBJECTIVE: To demonstrate how bladder ultrasound can be useful in completing morcellation during difficult Holmium Laser Enucleation of the Prostate (HoLEP). As HoLEP has emerged as a standard of care for the treatment of benign prostatic hyperplasia, multiple studies have reported the potentially catastrophic complication of bladder injury during morcellation. This video aims to assist any urologist performing HoLEP by providing step-by-step instruction for using ultrasound to complete morcellation safely. METHODS: Enucleation is performed using a 26-French continuous flow scope, off-set laser bridge with a laser stabilization catheter, and a 550 µm holmium laser fiber. Once the median and lateral lobes have been enucleated, the outer sheath is removed and the nephroscope is inserted to facilitate morcellation. Under dual inflow irrigation, the Piranha morcellator (Richard Wolf, Knittlingen, Germany) is introduced and set to the manufacturer's recommended settings of 1500 rpm. A 3.5-MHz convex abdominal ultrasound transducer (Hitachi Prosound Alpha 7; Hitachi Aloka Medical America, Wallingford, CT) under B-mode is used to visualize the bladder, predominantly in the sagittal orientation. Morcellation proceeds under simultaneous ultrasound and direct cystoscopic guidance. RESULTS: The distended bladder is visualized concurrently with the ultrasound and via the nephroscope as the Piranha engages the adenoma and begins morcellation. Once the adenoma is engaged, the operator then drops their hands to place the morcellator in the center of the bladder. Ultrasound provides real-time feedback as to the location of the morcellator in relation to the adenoma and bladder. CONCLUSION: This video highlights the use of intraoperative bladder ultrasound as a visual aid to assist during the morcellation portion of HoLEP. This proof of concept demonstrates that ultrasound can be an additional tool to utilize during difficult cases when cystoscopic visualization during morcellation is limited.


Asunto(s)
Complicaciones Intraoperatorias/prevención & control , Terapia por Láser/métodos , Morcelación/métodos , Prostatectomía/métodos , Vejiga Urinaria/diagnóstico por imagen , Humanos , Complicaciones Intraoperatorias/etiología , Terapia por Láser/efectos adversos , Terapia por Láser/instrumentación , Láseres de Estado Sólido/efectos adversos , Láseres de Estado Sólido/uso terapéutico , Masculino , Morcelación/efectos adversos , Morcelación/instrumentación , Prueba de Estudio Conceptual , Próstata/diagnóstico por imagen , Próstata/cirugía , Prostatectomía/efectos adversos , Prostatectomía/instrumentación , Hiperplasia Prostática/cirugía , Ultrasonografía , Vejiga Urinaria/lesiones
4.
Int J Radiat Oncol Biol Phys ; 106(1): 100-107, 2020 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-31627177

RESUMEN

PURPOSE: In patients with non-small cell lung cancer (NSCLC), concurrent chemoradiation therapy (CRT) exacerbates a cluster of difficult-to-manage symptoms, especially cancer-related fatigue. Minocycline is a readily available, low-cost antibiotic with antiinflammatory properties. We conducted a phase 2 randomized, double-blinded, placebo-controlled trial to investigate the effect of minocycline in reducing CRT-symptom burden in NSCLC. METHODS AND MATERIALS: Patients with NSCLC scheduled to receive CRT provided consent and were randomized to receive either minocycline (100 mg twice daily) or a matching placebo during 6 to 7 weeks of CRT. Patient-reported fatigue and other symptoms were assessed on MD Anderson Symptom Inventory weekly from the start of CRT for 12 weeks. The primary outcome was 12-week (±2 days) area under the curve for symptom burden, which was compared between treatment groups. RESULTS: Forty of 49 enrolled patients (80%) were evaluable (19 on minocycline and 21 on placebo). There were no grade 3 + adverse events related to the study medication. Fatigue was significantly reduced in the minocycline group compared with placebo group during the 12-week trial period (area under the curve = 31.2 ± 14.2 vs 45.0 ± 20.9, P = .011), with a large effect size (Cohen's d = 0.77). Pain (Cohen's d = 0.54) and shortness of breath (Cohen's d = 0.55) were also significantly reduced in the minocycline group (all P < .05). CONCLUSIONS: Minocycline during CRT for NSCLC was feasible, had a low toxicity profile, and yielded a clinically and statistically significant positive signal in reducing symptom burden related to NSCLC and CRT. This study is a proof of concept so a larger trial in CRT patients is warranted.


Asunto(s)
Antibacterianos/uso terapéutico , Antiinflamatorios no Esteroideos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Quimioradioterapia/efectos adversos , Fatiga/tratamiento farmacológico , Neoplasias Pulmonares/radioterapia , Minociclina/uso terapéutico , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , Carcinoma de Pulmón de Células no Pequeñas/complicaciones , Método Doble Ciego , Disnea/tratamiento farmacológico , Fatiga/etiología , Femenino , Humanos , Neoplasias Pulmonares/complicaciones , Masculino , Persona de Mediana Edad , Prueba de Estudio Conceptual , Estudios Prospectivos , Calidad de Vida
5.
Int J Cancer ; 146(1): 115-122, 2020 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-31211411

RESUMEN

Epigenetic transformations may provide early indicators for cancer and other disease. Specifically, the amount of genomic 5-hydroxymethylcytosine (5-hmC) was shown to be globally reduced in a wide range of cancers. The integration of this global biomarker into diagnostic workflows is hampered by the limitations of current 5-hmC quantification methods. Here we present and validate a fluorescence-based platform for high-throughput and cost-effective quantification of global genomic 5-hmC levels. We utilized the assay to characterize cancerous tissues based on their 5-hmC content, and observed a pronounced reduction in 5-hmC level in various cancer types. We present data for glioblastoma, colorectal cancer, multiple myeloma, chronic lymphocytic leukemia and pancreatic cancer, compared to corresponding controls. Potentially, the technique could also be used to follow response to treatment for personalized treatment selection. We present initial proof-of-concept data for treatment of familial adenomatous polyposis.


Asunto(s)
5-Metilcitosina/análogos & derivados , Biomarcadores de Tumor/metabolismo , Epigénesis Genética , Ensayos Analíticos de Alto Rendimiento/métodos , Neoplasias/genética , 5-Metilcitosina/metabolismo , Animales , Análisis Costo-Beneficio , Fluorescencia , Ensayos Analíticos de Alto Rendimiento/economía , Humanos , Ratones , Neoplasias/clasificación , Prueba de Estudio Conceptual
6.
Talanta ; 206: 120217, 2020 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-31514897

RESUMEN

MicroRNAs (miRNA) involve in regulating different physiological processes whose dysregulation is associated with a wide range of diseases including cancers, diabetes and cardiovascular problems. Herein, we report a direct, sensitive and highly selective detection assay for circulating microRNA (miRNA). This detection strategy employs magnetic nanoparticles as the reaction platform which can not only allow online pre-concentration and selective separation but also integrates ligation reaction with amplification to enhance the sensitivity of the detection assay. With the presence of the target miRNA, the locked nucleic acid (LNA)-modified molecular beacon (MB) opens up, exposing the binding sites at two ends. The 3'- and 5'-end of the MB responsible for the attachment onto the magnetic nanoparticles, and reporting probe for the attachment of the pair of amplification probes respectively. The ligase ligate RNA to DNA enhance the amplification efficiency. Upon labelled with intercalating fluorophores (YOYO-1) on the hybrids, the quantification of the target miRNA was determined by measuring the fluorescence intensity. A detection limit of 314 fM was achieved with trace amount of sample consumption (~20 µL). As a proof of concept, miRNA-149 was chosen as the target miRNA. This assay is capable of discriminating single-base and reliably quantifying circulating miRNA-149 in both healthy and cancer patient's serums. The result obtained was comparable with that of quantitative reverse transcription polymerase chain reaction (qRT-PCR), suggesting that this direct and sensitive assay can be served as a promising, non-invasive tool for early diagnosis of breast cancer and colorectal cancer.


Asunto(s)
MicroARN Circulante/sangre , MicroARNs/sangre , Microscopía Fluorescente/métodos , ARN Ligasa (ATP)/química , Proteínas Virales/química , Benzoxazoles/química , MicroARN Circulante/genética , ADN/química , ADN/genética , Colorantes Fluorescentes/química , Humanos , Sustancias Intercalantes/química , Límite de Detección , Nanopartículas de Magnetita/química , MicroARNs/genética , Hibridación de Ácido Nucleico , Oligonucleótidos/química , Oligonucleótidos/genética , Prueba de Estudio Conceptual , Compuestos de Quinolinio/química
8.
PLoS Genet ; 15(10): e1008353, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31671092

RESUMEN

Mendelian randomization (MR) is an established approach to evaluate the effect of an exposure on an outcome. The gene-by-environment (GxE) study design can be used to determine whether the genetic instrument affects the outcome through pathways other than via the exposure of interest (horizontal pleiotropy). MR phenome-wide association studies (MR-pheWAS) search for the effects of an exposure, and can be conducted in UK Biobank using the PHESANT package. In this proof-of-principle study, we introduce the novel GxE MR-pheWAS approach, that combines MR-pheWAS with the use of GxE interactions. This method aims to identify the presence of effects of an exposure while simultaneously investigating horizontal pleiotropy. We systematically test for the presence of causal effects of smoking heaviness-stratifying on smoking status (ever versus never)-as an exemplar. If a genetic variant is associated with smoking heaviness (but not smoking initiation), and this variant affects an outcome (at least partially) via tobacco intake, we would expect the effect of the variant on the outcome to differ in ever versus never smokers. We used PHESANT to test for the presence of effects of smoking heaviness, instrumented by genetic variant rs16969968, among never and ever smokers respectively, in UK Biobank. We ranked results by the strength of interaction between ever and never smokers. We replicated previously established effects of smoking heaviness, including detrimental effects on lung function. Novel results included a detrimental effect of heavier smoking on facial aging. We have demonstrated how GxE MR-pheWAS can be used to identify potential effects of an exposure, while simultaneously assessing whether results may be biased by horizontal pleiotropy.


Asunto(s)
Fumar Cigarrillos/epidemiología , Biología Computacional/métodos , Análisis de la Aleatorización Mendeliana/métodos , Envejecimiento de la Piel/efectos de los fármacos , Bancos de Muestras Biológicas , Fumar Cigarrillos/efectos adversos , Fumar Cigarrillos/genética , Interacción Gen-Ambiente , Pleiotropía Genética , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Prueba de Estudio Conceptual , Reino Unido/epidemiología
9.
Chem Commun (Camb) ; 56(1): 58-61, 2019 Dec 17.
Artículo en Inglés | MEDLINE | ID: mdl-31690925

RESUMEN

Herein, as a proof of concept, we developed the first enzymatic VIE fluorogenic probe for protein tyrosine phosphatase 1B (PTP1B). The detection and imaging of PTP1B using VIE in living cells were both realized. Particularly importantly, the designed probe herein provides a guideline and platform for the development of new VIE-based enzymatic probes.


Asunto(s)
Colorantes Fluorescentes/química , Organofosfatos/química , Fenazinas/química , Proteína Tirosina Fosfatasa no Receptora Tipo 1/análisis , Línea Celular Tumoral , Pruebas de Enzimas/métodos , Colorantes Fluorescentes/síntesis química , Humanos , Microscopía Confocal/métodos , Microscopía Fluorescente/métodos , Organofosfatos/síntesis química , Fenazinas/síntesis química , Prueba de Estudio Conceptual , Vibración
10.
Artículo en Inglés | MEDLINE | ID: mdl-31731218

RESUMEN

The improvement of sensitivity in headspace (HS) sampling of not very volatile analytes constitutes a challenge that has usually been approached through coupling with additional techniques. Here we propose a new methodology for increasing sensitivity through a multistep approach. This proof of concept is based on direct coupling of a headspace sampler with a programmed temperature vaporizer (PTV) and a gas chromatograph (GC), with mass spectrometry (MS) detection. Analytes are extracted from the same vial in a stepwise procedure, splitting the headspace generation time of conventional HS into four periods and using the PTV to cryogenically trap the analytes during the successive HS samplings. Solvent vent mode is mandatory in order to retain the analytes, purging the gas solvent at an adequate initial low temperature and flash-heating the PTV liner in a quick ramp (720 °C/min), once the HS samplings are finished. Linear aldehydes, from pentanal to decanal, possible biomarkers of several diseases have been selected as model compounds. This multiple HS method has been compared with conventional HS, and it has been validated in terms of linearity, limits of detection, repeatability, reproducibility and accuracy. The limits of detection (LOD) ranged from 0.004 to 0.159 µg/L. Enrichment factors (EF) in relation to the conventional HS method ranged from 3.0 to 6.7, except for pentanal (EF: 0.8), which is too volatile and polar to be trapped in the PTV with the multiple HS methodology. Similar enrichment factors were obtained in a urine sample.


Asunto(s)
Aldehídos/análisis , Cromatografía de Gases y Espectrometría de Masas/métodos , Diseño de Equipo , Cromatografía de Gases y Espectrometría de Masas/instrumentación , Calor , Límite de Detección , Modelos Lineales , Nebulizadores y Vaporizadores , Prueba de Estudio Conceptual , Reproducibilidad de los Resultados
11.
Analyst ; 144(22): 6721-6728, 2019 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-31612878

RESUMEN

The tympanic membrane (TM) is a dynamic structure that separates the middle ear from the external auditory canal. It is also integral for the transmission of sound waves. In this study, we demonstrate the feasibility of using Raman spectroscopy to identify early chemical changes resulting from inflammation in the TM that can serve as an indicator of acute otitis media. Bacterial lipopolysaccharide (LPS) was injected trans-tympanicaly in a murine model. Presence of inflammatory response was assessed with binocular microscopy, confirmed with histopathology and immunofluorescence staining. Successful discrimination suggesting spectral differences among the control and LPS treated groups was achieved using principal component analysis. Raman imaging revealed major differences in collagen distribution and nucleic acid content. Image segmentation analysis on the trichrome stained tissue sections was performed to corroborate the Raman spectra. The spectral co-localization study suggests changes in the expression of collagen IV specific signals in LPS treated samples. The overall findings of the study support prospective application of RS in the diagnosis and therapeutic monitoring of otitis media.


Asunto(s)
Otitis Media/diagnóstico , Membrana Timpánica/metabolismo , Animales , Femenino , Inflamación/inducido químicamente , Inflamación/diagnóstico , Lipopolisacáridos/farmacología , Ratones Endogámicos C57BL , Otitis Media/inducido químicamente , Prueba de Estudio Conceptual , Espectrometría Raman/métodos
12.
Heart Surg Forum ; 22(5): E380-E384, 2019 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-31596716

RESUMEN

OBJECTIVE: To explore the feasibility of endovascular reconstruction of aortic root including aortic valve, sinus of valsalva and ascending aorta by a single stent-graft, a novel valved stent-graft with two fenestrae for preserving the coronary arteries was designed and performed in-vitro on a pig heart based circulation simulating system. METHODS: Pig hearts were harvested from 30 healthy adult female pigs weighing between 60-65 kilograms. Before sacrifice, all the pigs received aortic computed tomography angiography (CTA) examinations and morphologic parameters of aortic root were measured. Then we customized the valved stent-grafts according to the CTA measurements. After the pig heart was fixed on the special platform according to the original orientation and connected to the circulation system, the stent graft was delivered through transapical access and covered the segment from aortic annulus to proximal part of aortic arch under DSA (digital subtraction angiography) guidance. Then changes of coronary flow before and after the procedure and fenestration alignment with coronary ostia were analyzed. RESULTS: The overall technical success rate was 100%. The valve functions tested by ultrasound were in good condition under 120 mmHg circulation pressure. The flow of left coronary artery (LCA) did not decrease, but increased after the stent-graft implantation (340 ± 2.06 mL/min versus 288 ± 5.29 mL/min, P < .05). Similarly, the flow of right coronary artery (RCA) also increased (392 ± 9.17 mL/min versus 348 ± 8.01 mL/min; P < .05). The final angiography confirmed that both coronary arteries were patent. When generally observed from outer wall of valsalva sinus, both RCA and LCA orifices were aligned with the fenestrae. In 4 cases, the autologous valve leaflets blocked nearly 20% of the LCA fenestra's area, but the flow did not significantly decrease in these cases. CONCLUSION: Stimulated on a pig heart-based circulation simulation system, the one-piece valved-fenestrated stent graft with a branch could be delivered via the transapical access and deployed accurately, which achieved endovascular reconstruction of aortic valve, sinus of valsalva and ascending aorta while preserving the coronary artery perfusion by fenestrations. More in-vivo experiments on animal models are mandatory to further verify its efficacy and safety.


Asunto(s)
Aorta Torácica/cirugía , Válvula Aórtica/cirugía , Procedimientos Endovasculares/métodos , Stents , Angiografía de Substracción Digital , Animales , Angiografía por Tomografía Computarizada , Circulación Coronaria , Vasos Coronarios/cirugía , Estudios de Factibilidad , Femenino , Técnicas In Vitro , Tratamientos Conservadores del Órgano/métodos , Prueba de Estudio Conceptual , Procedimientos Quirúrgicos Reconstructivos/métodos , Seno Aórtico/cirugía , Técnicas de Sutura , Porcinos
13.
Middle East Afr J Ophthalmol ; 26(3): 148-152, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31619902

RESUMEN

PURPOSE: Glaucoma drainage device surgery (GDDS) has gained popularity, with outcomes equivalent to trabeculectomy. Erosion of the tube through the overlying conjunctiva may occur in 5%-10% of eyes. Donor corneal tissue has been used as a patch graft for GDDS. MATERIALS AND METHODS: This was a prospective proof of concept study in 10 patients undergoing GDDS. From patients undergoing endothelial keratoplasty, the donor tissue (approximately 300 µ in thickness) was placed epithelial side down in a well and was allowed to soak in riboflavin solution (VibeX, Avedro, Waltham, MA, USA) for 15 min. This anterior corneal lenticule received 8 mW/cm2 ultraviolet (UV) irradiation applied for 15 min (total energy of 7.2 J/cm2). Each lenticule was then bisected and utilized for the two study participants. The tissue was sutured over the tube during the GDDS and then was covered with recipient conjunctiva as per the usual technique. Representative graft tissues were fixed and examined to determine the depth of cross-linking effect. The patients were followed for 1 year. RESULTS: Histology revealed no apparent demarcation line in the cross-linked grafts; this supported a full-thickness cross-linking treatment effect. There were no intra- or postoperative complications attributed to the graft tissue. No patient developed erosion or exposure of the tube during the 1-year follow-up. CONCLUSIONS: UV-riboflavin cross-linking of the corneal tissue patch graft material appears to be a safe modification when used in GDDS and warrants ongoing study. This method of patch graft can replace other costy methods used with GDD.


Asunto(s)
Colágeno/metabolismo , Córnea/efectos de los fármacos , Trasplante de Córnea/métodos , Reactivos de Enlaces Cruzados , Implantes de Drenaje de Glaucoma , Glaucoma de Ángulo Abierto/cirugía , Adulto , Anciano , Córnea/metabolismo , Femenino , Humanos , Presión Intraocular/fisiología , Masculino , Persona de Mediana Edad , Fármacos Fotosensibilizantes/uso terapéutico , Proyectos Piloto , Complicaciones Posoperatorias , Prueba de Estudio Conceptual , Estudios Prospectivos , Riboflavina/uso terapéutico , Donantes de Tejidos , Rayos Ultravioleta , Adulto Joven
14.
Scand J Immunol ; 90(6): e12821, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31589347

RESUMEN

As a result of the cancer immunotherapy revolution, more than 2000 immuno-oncology agents are currently being tested or are in use to improve responses. Not unexpectedly, the 2018 Nobel Prize in Physiology or Medicine was awarded to James P. Allison and Tasuku Honjo for their development of cancer therapy by the blockade of co-inhibitory signals. Unfortunately, manipulation of the co-inhibitory receptors has also resulted in a safety issue: widespread iatrogenic immune-related adverse events (irAEs). Autoimmunity is emerging as the nemesis of immunotherapy. Originally, it was assumed that CTLA-4 blockade selectively targets T cells relevant to the antitumour immune response. However, an uncontrolled pan T cell activation was induced compromising tolerance to healthy self-tissues. The irAEs are very similar to that of a chronic graft-versus-host-disease (GVHD) reaction following allogeneic bone marrow transplantation (BMT). We hypothesized that ipilimumab induced a graft-versus-malignancy (GVM) effect, which eradicated metastatic melanoma in a minority of patients, but also involved an auto-GVHD reaction that resulted in widespread autoimmunity in the majority. Therefore, we argued for a profound theoretical point against the consensus of experts. The task is not to desperately put the genie back in the bottle by immune-suppressive treatments, but instead to harness the autoimmune forces. In this way, the same goal could be achieved by an antibody as by the adoptive transfer of alloreactive donor lymphocytes, but without severe GVHD. The proof-of-principle of a low-dose-combination immune checkpoint therapy, consisting only of approved drugs and treatments, was demonstrated in 111 stage IV cancer patients.


Asunto(s)
Antineoplásicos Inmunológicos/uso terapéutico , Autoinmunidad/efectos de los fármacos , Biomarcadores de Tumor/antagonistas & inhibidores , Terapia Molecular Dirigida , Neoplasias/tratamiento farmacológico , Neoplasias/inmunología , Antineoplásicos Inmunológicos/administración & dosificación , Antineoplásicos Inmunológicos/efectos adversos , Antígeno CTLA-4/antagonistas & inhibidores , Antígeno CTLA-4/genética , Antígeno CTLA-4/metabolismo , Humanos , Activación de Linfocitos/efectos de los fármacos , Activación de Linfocitos/inmunología , Metástasis de la Neoplasia , Estadificación de Neoplasias , Neoplasias/genética , Neoplasias/patología , Uso Fuera de lo Indicado , Prueba de Estudio Conceptual , Transducción de Señal/efectos de los fármacos , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología , Linfocitos T/metabolismo , Resultado del Tratamiento
15.
Plast Reconstr Surg ; 144(4): 565e-574e, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31568284

RESUMEN

BACKGROUND: Studies based on large-volume databases have made significant contributions to research on breast cancer surgery. To date, no comparison between large-volume databases has been made internationally. This is the first proof-of-concept study exploring the feasibility of combining two existing operational databases of The Netherlands and the United States, focusing on breast cancer care and immediate breast reconstruction specifically.313/291 METHODS:: The National Breast Cancer Organization The Netherlands Breast Cancer Audit (NBCA) (2011 to 2015) and the U.S. Surveillance, Epidemiology, and End Results (SEER) database (2010 to 2013) were compared on structure and content. Data variables were grouped into general, treatment-specific, cancer-specific, and follow-up variables and were matched. As proof-of-concept, mastectomy and immediate breast reconstruction rates in patients diagnosed with invasive breast cancer or ductal carcinoma in situ were analyzed. RESULTS: The NBCA included 115 variables and SEER included 112. The NBCA included significantly more treatment-specific variables (n = 46 versus 6), whereas the SEER database included more cancer-specific variables (n = 74 versus 26). In patients diagnosed with breast cancer or ductal carcinoma in situ, immediate breast reconstruction was performed in 19.3 percent and 24.0 percent of the breast cancer cohort and 44.0 percent and 35.3 percent of the ductal carcinoma in situ cohort in the NBCA and SEER, respectively. Immediate breast reconstruction rates increased significantly over time in both data sets. CONCLUSIONS: This study provides a first overview of available registry data on breast cancer care in The Netherlands and the United States, and revealed limited data on treatment in the United States. Comparison of treatment patterns of immediate breast reconstruction showed interesting differences. The authors advocate the urgency for an international database with alignment of (treatment) variables to improve quality of breast cancer care for patients across the globe.


Asunto(s)
Neoplasias de la Mama/cirugía , Carcinoma Intraductal no Infiltrante/cirugía , Mamoplastia/métodos , Mamoplastia/normas , Mastectomía , Calidad de la Atención de Salud , Adulto , Anciano , Neoplasias de la Mama/patología , Bases de Datos Factuales , Estudios de Factibilidad , Femenino , Humanos , Persona de Mediana Edad , Invasividad Neoplásica , Países Bajos , Prueba de Estudio Conceptual , Sistema de Registros , Factores de Tiempo , Estados Unidos
16.
Prensa méd. argent ; 105(9 especial): 621-627, oct 2019. fig
Artículo en Inglés | LILACS, BINACIS | ID: biblio-1046797

RESUMEN

Chronic recurrent oral aphthae in residents living in an ecologically unfavourable region are characterized by a permanent course and prolonged recovery processes of regeneration of pathological elements of the oral mucosa. Using the microbiological method and modern test systems, it has been found that on the surface of aphthae an extremely diverse state of the oral microbiota is determined and its types are diverse. Trigger mechanisms have been determined. The role of representatives of various types of microorganisms - enterococci, staphylococci, streptococci, yeast-like fungi of the genus Candida (C. albicans) and obligate-anaerobes in the development of recurrent oral aphthae has been established. The data obtained can serve as an indication for the development of modern treatment and preventive measures regarding this category of patients.


Asunto(s)
Humanos , Estomatitis Aftosa/microbiología , Estomatitis Aftosa/prevención & control , Estomatitis Aftosa/terapia , Microbiota/inmunología , Prueba de Estudio Conceptual , Mucosa Bucal/microbiología
17.
Acta Diabetol ; 56(12): 1333-1339, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31506721

RESUMEN

AIMS: This study aimed to evaluate the effect of pioglitazone on brown adipose tissue function and hypothalamic gliosis in humans. Brown adipose tissue and the hypothalamus are regarded as important potential pharmacological targets to metabolic diseases, and defining the impact of current therapies on their structure and/or function could provide therapeutic advance in this field. METHODS: Six patients with type 2 diabetes were treated for 24 weeks with pioglitazone 30 mg/day as an add-on therapy. Brown adipose tissue glucose uptake and volume were determined using 18F-FDG PET/CT scans; hypothalamic gliosis was determined using MRI scans; blood was collected for hormone and biochemistry measurements. All tests were performed at inclusion and six months after pioglitazone introduction. RESULTS: Pioglitazone treatment led to a significant 3% body mass increase. There were neither changes in cold-induced brown adipose tissue glucose uptake and volume nor changes in hypothalamic gliosis. CONCLUSIONS: This is a proof-of-concept study that provides clinical evidence for a lack of action of a thiazolidinedione, pioglitazone, to promote homogeneous and measurable changes in brown adipose tissue volume and also in hypothalamic gliosis after 6 months of treatment.


Asunto(s)
Tejido Adiposo Pardo/efectos de los fármacos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Gliosis/prevención & control , Hipotálamo/efectos de los fármacos , Hipotálamo/patología , Pioglitazona/farmacología , Tejido Adiposo Pardo/diagnóstico por imagen , Tejido Adiposo Pardo/patología , Adulto , Anciano , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/patología , Quimioterapia Combinada , Femenino , Fluorodesoxiglucosa F18 , Gliosis/diagnóstico , Gliosis/patología , Humanos , Hipotálamo/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Obesidad/complicaciones , Obesidad/diagnóstico , Obesidad/tratamiento farmacológico , Obesidad/patología , Tamaño de los Órganos/efectos de los fármacos , Sobrepeso/complicaciones , Sobrepeso/diagnóstico , Sobrepeso/tratamiento farmacológico , Sobrepeso/patología , Pioglitazona/administración & dosificación , Tomografía Computarizada por Tomografía de Emisión de Positrones , Prueba de Estudio Conceptual , Tiazolidinedionas/administración & dosificación , Tiazolidinedionas/farmacología
18.
Chem Commun (Camb) ; 55(80): 12036-12039, 2019 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-31531454

RESUMEN

While commercially available suncare products are effective at absorbing ultraviolet (UV)-light, recent studies indicate systemic toxicities associated with many traditional chemical and physical UV-filters. We demonstrate the application of xanthommatin, a biochrome present in arthropods and cephalopods, as an alternative chemical UV-filter that is cytocompatible while maintaining its photostability and photoprotective properties.


Asunto(s)
Antioxidantes/farmacología , Oxazinas/farmacología , Piel/efectos de la radiación , Protectores Solares/farmacología , Xantenos/farmacología , Animales , Antioxidantes/química , Supervivencia Celular/efectos de los fármacos , Daño del ADN , Dimetilpolisiloxanos/química , Humanos , Ratones , Células 3T3 NIH , Oxazinas/química , Prueba de Estudio Conceptual , Piel/citología , Protectores Solares/química , Rayos Ultravioleta , Xantenos/química
19.
Nat Commun ; 10(1): 4336, 2019 09 24.
Artículo en Inglés | MEDLINE | ID: mdl-31551496

RESUMEN

New strategies with high antimicrobial efficacy against multidrug-resistant bacteria are urgently desired. Herein, we describe a smart triple-functional nanostructure, namely TRIDENT (Thermo-Responsive-Inspired Drug-Delivery Nano-Transporter), for reliable bacterial eradication. The robust antibacterial effectiveness is attributed to the integrated fluorescence monitoring and synergistic chemo-photothermal killing. We notice that temperature rises generated by near-infrared irradiation did not only melt the nanotransporter via a phase change mechanism, but also irreversibly damaged bacterial membranes to facilitate imipenem permeation, thus interfering with cell wall biosynthesis and eventually leading to rapid bacterial death. Both in vitro and in vivo evidence demonstrate that even low doses of imipenem-encapsulated TRIDENT could eradicate clinical methicillin-resistant Staphylococcus aureus, whereas imipenem alone had limited effect. Due to rapid recovery of infected sites and good biosafety we envision a universal antimicrobial platform to fight against multidrug-resistant or extremely drug-resistant bacteria.


Asunto(s)
Antibacterianos/administración & dosificación , Infecciones Bacterianas/terapia , Sistemas de Liberación de Medicamentos , Imipenem/administración & dosificación , Infecciones Cutáneas Estafilocócicas/terapia , Animales , Antibacterianos/farmacología , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Imipenem/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Ratones , Pruebas de Sensibilidad Microbiana , Nanoestructuras/química , Fototerapia/efectos adversos , Fototerapia/métodos , Prueba de Estudio Conceptual
20.
Eur J Med Chem ; 183: 111683, 2019 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-31514060

RESUMEN

While photodynamic therapy is known for significant advantages over conventional cancer therapies, its dependence on light has limited it to treating tumors on or just under the skin or on the outer lining of organs/cavities. Herein, we have developed a single-molecule photosensitizer capable of intracellular self-activation and with potential tumor-selectivity due to a chemiluminescent reaction involving only a cancer marker. Thus, the photosensitizer is directly chemiexcited to a triplet excited state capable of generating singlet oxygen, without requiring either a light source or any catalyst/co-factor. Cytotoxicity assays involving the photosensitizer show significant toxicity toward tumor cells, even better than reference drugs, while not inducing toxicity toward normal cells. This work provides a proof-of-concept for a novel type of photosensitizer that eliminates the current restrictions that photodynamic therapy presents regarding tumor size and localization.


Asunto(s)
Imidazoles/química , Neoplasias/tratamiento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/química , Pirazinas/química , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Simulación por Computador , Humanos , Luz , Fármacos Fotosensibilizantes/farmacología , Prueba de Estudio Conceptual , Pirazinas/farmacología , Oxígeno Singlete/metabolismo , Termodinámica
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