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1.
Sci Rep ; 14(1): 4454, 2024 02 23.
Artículo en Inglés | MEDLINE | ID: mdl-38396070

RESUMEN

The impact of emotions on human behavior is substantial, and the ability to recognize people's feelings has a wide range of practical applications including education. Here, the methods and tools of education are being calibrated according to the data gained over electroencephalogram (EEG) signals. The issue of which design tools would be ideal in the future of interior architecture education, is an uncertain field. It is important to measure the students' emotional states while using manual and digital design tools to determine the different impacts. Brain-computer interfaces have made it possible to monitor emotional states in a way that is both convenient and economical. In the research of emotion recognition, EEG signals have been employed, and the resulting literature explains basic emotions as well as complicated scenarios that are created from the combination of numerous basic emotions. The objective of this study is to investigate the emotional states and degrees of attachment experienced by interior architecture students while engaging in their design processes. This includes examining the use of 2D or 3D tools, whether manual or digital, and identifying any changes in design tool usage and behaviors that may be influenced by different teaching techniques. Accordingly, the hierarchical clustering which is a technique used in data analysis to group objects into a hierarchical structure of clusters based on their similarities has been conducted.


Asunto(s)
Electroencefalografía , Emociones , Humanos , Proyectos Piloto , Emociones/fisiología , Electroencefalografía/métodos , Estudiantes , Reconocimiento en Psicología
2.
ACS Appl Bio Mater ; 7(3): 1878-1887, 2024 03 18.
Artículo en Inglés | MEDLINE | ID: mdl-38414330

RESUMEN

Cancer is one of the most actively researched diseases having a high mortality rate when not detected at an early stage. Thus, rapid, simultaneous, and sensitive quantification of cancer biomarkers plays an important role in early diagnosis, with patient impact to disability adjusted life years. Herein, a diatomite-based SERS flexible platform for the rapid and sensitive detection of circulating cancer-specific protein biomarkers in serum is presented. In this approach, diatomite/AgNPs strips with maximum SERS activity prepared using the layer-by-layer (LbL) technique were modified with specific antibodies, and specific antigens (HER2, CA15-3, PSA, and MUC4) were captured and detected. By using Raman probes specific to the captured antigens in serum, a SERS limit of detection (LOD) of 0.1 ng/mL was measured (calculated LOD < 0.1 ng/mL). This value is lower than the cutoff amount of cancer antigens in the person's blood. The specificity for the antigens of each antibody was calculated to be higher than 95%. As a result, an immunosensor for rapid detection of cancer biomarkers in serum with good specificity, high sensitivity, good reproducibility, and low cost has been demonstrated. Overall, we show that the prepared diatomite-based SERS substrate with a high surface-to-volume ratio is a useable platform for immunoassay tests.


Asunto(s)
Técnicas Biosensibles , Tierra de Diatomeas , Neoplasias , Humanos , Biomarcadores de Tumor , Reproducibilidad de los Resultados , Inmunoensayo , Anticuerpos , Neoplasias/diagnóstico
3.
Cureus ; 15(8): e44192, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37641725

RESUMEN

Spinal epidural hematomas (SEHs)are space-occupying lesions that exert pressure on the spinal cord by rapidly accumulating blood between the dura and bone or ligament components. The annual incidence of spontaneous epidural hematoma is estimated to be one in one million. The predominant symptoms are back pain or neurological impairment, including sensory, motor, or autonomic dysfunction of the limbs below the hematoma level. Depending on the level and size of the hematoma and the affected cord, they cause neurological deficits. Neurological deficits are often reversible if diagnosed and treated early with surgical decompression. However, neurological deficits can become permanent if the patient is not operated on timely, and paraplegia or quadriplegia may occur. A 53-year-old man presented to our emergency department with acute-onset back pain and 36-hour-long, rapidly progressive paraparesis of both legs. On T1- and T2-weighted MRI scans, a hyperacute SEH was found as iso/hyperintense and hyperintense, respectively. Immediate decompressive laminectomy from T10 to L2 and hematoma evacuation were performed. It was challenging to remove the hematoma due to its firm consistency. Before performing a bilateral total laminectomy at five levels, the posterior spine was stabilized between T10 and L3 using transpedicular screws. Within 24 hours, the motor function of the lower limbs increased considerably. The patient could sit on a chair because of posterior stability. In addition to the importance of early diagnosis using imaging techniques, planning the extension of SEH surgery is crucial for the patient's postoperative neurological recovery.

4.
Nanoscale ; 15(33): 13770-13783, 2023 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-37578149

RESUMEN

Surface-enhanced Raman scattering (SERS) is an emerging spectroscopy technique for detecting and characterizing chemical or biological structures in the vicinity of plasmonic nanostructures. Colloidal, solid, and flexible nanostructures are widely used in SERS experiments to enhance the Raman intensity. The nanostructure used in SERS is one of the main influencing parameters and a growing research area. Fabrication of simple and cheap SERS substrates with a high enhancement factor is desired. In this study, we fabricated a reproducible, cheap, and flexible SERS active strip by coating natural diatomite (biosilica) with silver nanoparticles (AgNPs) using the layer-by-layer assembly method and the fabricated strip is used for the label-free identification of circulating cancer protein biomarkers. SERS active strips were fabricated having different numbers of AgNP layers on natural diatomite and comprehensive characterization techniques such as X-ray diffraction (XRD), scanning electron microscopy (SEM), and UV/vis absorption spectrophotometry were used. SERS activities of the strips depending on the number of layers were evaluated using 4-aminothiophenol (4-ATP) and rhodamine 6G (Rh6G) molecules. We found that the SERS intensity is strongly dependent on the number of AgNP layers, with the maximum SERS intensity obtained from the strip with 5 layers of AgNPs, having a 2.0 × 105 enhancement factor. The strip with the highest SERS activity was used for the label-free identification of circulating cancer protein biomarkers (HER2, CA15-3, PSA, MUC4, and CA27-29). The results demonstrate that the fabricated strip can help in the effective label-free identification of circulating protein biomarkers and open new directions for SERS-based label-free biosensing applications.


Asunto(s)
Nanopartículas del Metal , Neoplasias , Humanos , Nanopartículas del Metal/química , Biomarcadores de Tumor , Plata/química , Espectrometría Raman/métodos
5.
Acta Otolaryngol ; 143(4): 346-351, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37067345

RESUMEN

BACKGROUND: Necessity of new and alternative treatments in traumatic facial nerve injury. AIMS/OBJECTIVE: In this experimental study, we aimed to evaluate the histopathologic and functional effects of methylprednisolone, hyperbaric oxygen and hesperidin + diosmin treatments on traumatic facial nerve regeneration in rats. METHODS: After facial nerve injury, five groups were formed with eight rats in each group: Group 1 (negative control), 2 (operation), 3 (corticosteroid), 4 (hyperbaric oxygen), 5 (hesperidin + diosmin). Blink reflex of rats evaluated a day after the operation and at the first, second and third weeks. Facial nerve samples from sacrificed animals were examined under a light microscope. RESULTS: According to our results, in group 4; axonal degeneration and vascular congestion were significantly lower than group 2 and 3, and myelin sheath thickness was significantly higher than group 3. In group 5; axonal degeneration was significantly lower than group 2 and vascular congestion was significantly lower than group 2 and 3. In terms of functional recovery; there was no statistically significant difference between the groups. CONCLUSIONS AND SIGNIFICANCE: It has been shown that both hyperbaric oxygen and hesperidin + diosmin treatments have positive effects on facial nerve regeneration. Both treatments may be good alternatives for ameliorating traumatic nerve injury, but these treatment modalities need to be further explored.


Asunto(s)
Diosmina , Traumatismos del Nervio Facial , Hesperidina , Oxigenoterapia Hiperbárica , Ratas , Animales , Metilprednisolona/farmacología , Hesperidina/farmacología , Diosmina/farmacología , Modelos Animales , Nervio Facial/patología , Regeneración Nerviosa
6.
Aesthetic Plast Surg ; 47(2): 728-734, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36302983

RESUMEN

BACKGROUND: Dorsal preservation techniques have been preferred and gained popularity in recent years. The current study compares the effects of dorsal preservation and dorsal reduction rhinoplasty on nasal patency and aesthetic outcomes by using Patient-Reported Outcome Measures (PROMs) and rhinomanometry. To our knowledge, this is the first study to compare dorsal preservation and dorsal reduction techniques with rhinomanometry. METHODS: This is a prospective study of 34 patients who underwent rhinoplasty between January 2021-June 2022. The patients were randomly selected preoperatively and divided into two groups as structural rhinoplasty (SR) and preservation rhinoplasty (PR). Nasal Obstruction and Symptom Evaluation (NOSE), Standardized Cosmesis and Health Nasal Outcomes Survey (SCHNOS) scales and rhinomanometric evaluation were performed preoperatively, at 3rd month and 12th month postoperatively. RESULTS: Nineteen patients (10 female, 9 male) were in SR group, 15 patients (7 female, 8 male) were in PR group. There was not significant difference in terms of age and gender between groups. In both groups, NOSE, SCHNOS-O and SCHNOS-C results were found to be significantly lower at postoperative 3rd and 12th month compared to preoperatively (p < 0.001 for the entire SR group, p = 0.001 for the entire PR group). There was no significant difference between groups in terms of PROMs. Mean total nasal volume (TNV) at 12th month were statistically higher than preoperative value in PR group (p = 0.031). Also there was no significant difference in SR group and between groups in terms of rhinomanometry results. CONCLUSION: Dorsal preservation with pushdown technique provides good functional and aesthetic results comparable with structural rhinoplasty. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . A well-designed prospective clinical trial.


Asunto(s)
Obstrucción Nasal , Rinoplastia , Humanos , Masculino , Femenino , Rinoplastia/métodos , Estudios Prospectivos , Obstrucción Nasal/diagnóstico , Obstrucción Nasal/cirugía , Rinomanometría , Evaluación de Síntomas , Resultado del Tratamiento , Estética , Tabique Nasal/cirugía
7.
Anal Chim Acta ; 1221: 340094, 2022 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-35934394

RESUMEN

Colistin-resistant Klebsiella pneumoniae (ColR-Kp) causes high mortality rates since colistin is used as the last-line antibiotic against multi-drug resistant Gram-negative bacteria. To reduce infections and mortality rates caused by ColR-Kp fast and reliable detection techniques are vital. In this study, we used a label-free surface-enhanced Raman scattering (SERS)-based sensor with machine learning algorithms to discriminate colistin-resistant and susceptible strains of K. pneumoniae. A total of 16 K. pneumoniae strains were incubated in tryptic soy broth (TSB) for 4 h. Collected SERS spectra of ColR-Kp and colistin susceptible K. pneumoniae (ColS-Kp) have shown some spectral differences that hard to discriminate by the naked eye. To extract discriminative features from the dataset, autoencoder and principal component analysis (PCA) that extract features in a non-linear and linear manner, respectively were performed. Extracted features were fed into the support vector machine (SVM) classifier to discriminate K. pneumoniae strains. Classifier performance was evaluated by using features extracted by each feature extraction techniques. Classification results of SVM classifier with extracted features by an autoencoder (autoencoder-SVM) has shown better performance than SVM classifier with extracted features by PCA (PCA-SVM). The accuracy, sensitivity, specificity, and area under curve (AUC) value of the autoencoder-SVM model were found as 94%, 94.2%, 93.8%, and 0.98, respectively. Furthermore, the autoencoder-SVM model has demonstrated statistically significantly better classifier performance than PCA-SVM in terms of accuracy and AUC values. These results illustrate that non-linear features can be more discriminative than linear ones to determine SERS spectral data of antibiotic-resistant and susceptible bacteria. Our methodological approach enables rapid and high accuracy detection of ColR-Kp and ColS-Kp, suggesting that this can be a promising tool to limit colistin resistance.


Asunto(s)
Infecciones por Klebsiella , Klebsiella pneumoniae , Antibacterianos/farmacología , Colistina/farmacología , Humanos , Infecciones por Klebsiella/tratamiento farmacológico , Infecciones por Klebsiella/microbiología , Aprendizaje Automático , Pruebas de Sensibilidad Microbiana
8.
Acta Otolaryngol ; 141(11): 989-993, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34694199

RESUMEN

BACKGROUND: The effect of Covid-19 infection on nasal mucociliary clearance (MCC) is unknown. AIMS/OBJECTIVES: The aim of this study is to investigate the relationship between Covid-19 and nasal MCC in terms of smoking, Covid-19 symptoms and treatment. METHODS: Thirty-six patients who were hospitalized in the pandemic ward due to Covid-19 and 36 volunteers (Covid-19 negative test result) who presented to the otolaryngology outpatient clinic with non-nasal symptoms were included in this study. The Saccharin test was performed in both groups to evaluate nasal MCC. RESULTS: The patients and control groups were not significantly different in terms of age and gender. The nasal MCC time was significantly higher in the patient group compared to the control group (19.18 ± 10.84 min and 13.78 ± 8.18 min, p = .003). CONCLUSIONS AND SIGNIFICANCE: In this study, we found that Covid-19 prolonged nasal MCC time regardless of age. We suggest that corticosteroids should be included in the treatment of Covid-19, both with its symptom reduction and its positive effect on MCC duration.


Asunto(s)
COVID-19/fisiopatología , Depuración Mucociliar/fisiología , Mucosa Nasal/fisiopatología , Fumar/fisiopatología , Corticoesteroides/farmacología , Corticoesteroides/uso terapéutico , Adulto , Amidas/uso terapéutico , Antivirales/uso terapéutico , COVID-19/complicaciones , Estudios de Casos y Controles , Femenino , Humanos , Hidroxicloroquina/efectos adversos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Depuración Mucociliar/efectos de los fármacos , Pirazinas/uso terapéutico , Tratamiento Farmacológico de COVID-19
9.
Sci Rep ; 11(1): 18444, 2021 09 16.
Artículo en Inglés | MEDLINE | ID: mdl-34531449

RESUMEN

Over the past year, the world's attention has focused on combating COVID-19 disease, but the other threat waiting at the door-antimicrobial resistance should not be forgotten. Although making the diagnosis rapidly and accurately is crucial in preventing antibiotic resistance development, bacterial identification techniques include some challenging processes. To address this challenge, we proposed a deep neural network (DNN) that can discriminate antibiotic-resistant bacteria using surface-enhanced Raman spectroscopy (SERS). Stacked autoencoder (SAE)-based DNN was used for the rapid identification of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive S. aureus (MSSA) bacteria using a label-free SERS technique. The performance of the DNN was compared with traditional classifiers. Since the SERS technique provides high signal-to-noise ratio (SNR) data, some subtle differences were found between MRSA and MSSA in relative band intensities. SAE-based DNN can learn features from raw data and classify them with an accuracy of 97.66%. Moreover, the model discriminates bacteria with an area under curve (AUC) of 0.99. Compared to traditional classifiers, SAE-based DNN was found superior in accuracy and AUC values. The obtained results are also supported by statistical analysis. These results demonstrate that deep learning has great potential to characterize and detect antibiotic-resistant bacteria by using SERS spectral data.


Asunto(s)
Resistencia a la Meticilina , Staphylococcus aureus/clasificación , Staphylococcus aureus/crecimiento & desarrollo , Aprendizaje Profundo , Análisis Discriminante , Humanos , Nanopartículas del Metal/química , Pruebas de Sensibilidad Microbiana , Redes Neurales de la Computación , Relación Señal-Ruido , Plata/química , Espectrometría Raman , Staphylococcus aureus/efectos de los fármacos , Máquina de Vectores de Soporte
10.
Eur Arch Otorhinolaryngol ; 278(9): 3345-3349, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33452622

RESUMEN

PURPOSE: Nasal polyp is originating from the nasal mucosa or paranasal sinus mucosa. In our study, it was aimed to investigate the possible effects of inflammatory cytokines Interleukin-13 (IL-13), IL-25, IL-33 and Syndecan-1 (SDC-1) in the pathogenesis process of nasal polyp and relationship between these parameters and disease severity. METHODS: Our study was designed as a prospective case-control study. Patients diagnosed with nasal polyp were included in the patient group. The control group comprised volunteers with age and gender compatibility who does not have the disease. IL-13, IL-25, IL-33 and SDC-1 levels were detected in serum samples using enzyme-linked immunosorbent assay method. Nasal polyp disease severity was evaluated by means of "Sino-Nasal Outcome Test-22", "Lund-Mackay Score" and "Lund-Kennedy Score". RESULTS: In this study, 35 patients, 29 controls, a total of 64 participants were included. Our evaluation revealed that all cytokine levels in the patient group were statistically significantly higher than the control group (p < 0.05). However, there was no correlation found between scoring methods and cytokine levels (p > 0.05). CONCLUSION: The increase in cytokine levels in the patient group suggested that cytokine-mediated inflammation processes may be effective in nasal polyp pathogenesis.


Asunto(s)
Pólipos Nasales , Rinitis , Estudios de Casos y Controles , Enfermedad Crónica , Citocinas , Humanos , Estudios Prospectivos , Índice de Severidad de la Enfermedad
11.
Turk J Orthod ; 34(3): 163-169, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35110186

RESUMEN

OBJECTIVE: To compare Streptococcus mutans colonization between low-friction elastomeric ligatures and to correlate microbial colonization levels with the surface roughness status. METHODS: The study included 160 premolars of 10 patients. During the study period, which consisted of 4 sessions each lasting 4 weeks, the ligature types Slide™ Low-Friction Ligature (Leone, Firenze, Italy), Tough-O Energy™ (Rocky Mountain Orthodontics, Denver, USA), and Sili Ties™ (Dentsply Sirona, Surrey KT13 0NY, UK), and steel ligatures (American Orthodontics, Sheboygan, USA) as a control, were fixed to the premolar teeth by clockwise rotation among the jaw quadrants. The plaque index (PI) and gingival index (GI) were obtained before bonding (T0), 6 weeks after bonding (T1), and subsequently every 4 weeks (T2, T3, T4). Presence of S. mutans was analyzed by real-time polymerase chain reaction at T1, T2, T3, T4. Surface roughness was evaluated with Atomic Force Microscopy (AFM) before ligation (Ra0) and after (Ra1) ligation. The paired t-test, ANOVA, repeated measures of ANOVA, and the Kruskal-Wallis test were used for the statistical analysis. RESULTS: S. mutans colonization was significantly higher on the Slide group (P < .05). The lowest Ra0 was seen in Slide and the highest was seen in the Tough-O Energy group. There was no correlation between S. mutans colonization and Ra1 parameters of elastomeric groups (P > .05). CONCLUSION: S. mutans colonization showed variations in low-friction elastomeric ligatures independent of surface roughness. Ringshaped low-friction elastomeric ligatures were not different from the steel ligature in terms of S. mutans colonization.

12.
Analyst ; 145(23): 7559-7570, 2020 Nov 23.
Artículo en Inglés | MEDLINE | ID: mdl-33135033

RESUMEN

To combat antibiotic resistance, it is extremely important to select the right antibiotic by performing rapid diagnosis of pathogens. Traditional techniques require complicated sample preparation and time-consuming processes which are not suitable for rapid diagnosis. To address this problem, we used surface-enhanced Raman spectroscopy combined with machine learning techniques for rapid identification of methicillin-resistant and methicillin-sensitive Gram-positive Staphylococcus aureus strains and Gram-negative Legionella pneumophila (control group). A total of 10 methicillin-resistant S. aureus (MRSA), 3 methicillin-sensitive S. aureus (MSSA) and 6 L. pneumophila isolates were used. The obtained spectra indicated high reproducibility and repeatability with a high signal to noise ratio. Principal component analysis (PCA), hierarchical cluster analysis (HCA), and various supervised classification algorithms were used to discriminate both S. aureus strains and L. pneumophila. Although there were no noteworthy differences between MRSA and MSSA spectra when viewed with the naked eye, some peak intensity ratios such as 732/958, 732/1333, and 732/1450 proved that there could be a significant indicator showing the difference between them. The k-nearest neighbors (kNN) classification algorithm showed superior classification performance with 97.8% accuracy among the traditional classifiers including support vector machine (SVM), decision tree (DT), and naïve Bayes (NB). Our results indicate that SERS combined with machine learning can be used for the detection of antibiotic-resistant and susceptible bacteria and this technique is a very promising tool for clinical applications.


Asunto(s)
Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Antibacterianos/farmacología , Bacterias , Teorema de Bayes , Humanos , Aprendizaje Automático , Pruebas de Sensibilidad Microbiana , Reproducibilidad de los Resultados , Espectrometría Raman , Staphylococcus aureus
13.
Neurol Res ; 42(12): 1061-1069, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32715947

RESUMEN

OBJECTIVES: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively triggers apoptosis in cancer cells, but not in normal cells. Resistance of glioblastoma cells to TRAIL is a major obstacle for successful clinical treatment of TRAIL. Thus, there is an essential requirement for novel approaches to sensitize TRAIL resistance. Silver nanoparticles (AgNPs) are one of the most promising nanomaterials that show immense antitumor potential via targeting various cellular and molecular processes; however, the effects of AgNPs on TRAIL sensitivity in cancer cells remain unclear. Therefore, we hypothesized that TRAIL-conjugated AgNPs (TRAIL-AgNPs) can overcome TRAIL resistance through inducing death receptor activation in glioblastoma cells, but not normal cells. METHODS: In this study, the therapeutic effect of TRAIL-AgNPs is investigated by analyzing the cell viability, caspase activity, and CHK1 gene expression in T98 G TRAIL-Sensitive (TS) and T98 G TRAIL-Resistant (TR) glioblastoma cells. RESULTS: It is found that TRAIL-AgNPs are more toxic compared to TRAIL and AgNPs treatments alone on TR cells. While TRAIL and AgNPs alone do not enhance the caspase activity, conjugation of TRAIL to AgNPs increases the caspase activity in TR cells. Moreover, the TRAIL-AgNPs-treated TR cells show less CHK1 expression compared to the TRAIL treatment. CONCLUSION: These results suggest that TRAIL sensitivity of TR cells can be enhanced by conjugation of TRAIL with AgNPs, which would be a novel therapeutic approach to sensitize TRAIL resistance.


Asunto(s)
Supervivencia Celular/efectos de los fármacos , Reparación del ADN/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Glioblastoma/metabolismo , Plata/farmacología , Apoptosis/efectos de los fármacos , Proteínas Reguladoras de la Apoptosis/genética , Reparación del ADN/genética , Regulación Neoplásica de la Expresión Génica/genética , Glioblastoma/genética , Humanos , Plata/metabolismo , Ligando Inductor de Apoptosis Relacionado con TNF/genética , Ligando Inductor de Apoptosis Relacionado con TNF/farmacología
14.
ACS Med Chem Lett ; 10(1): 50-55, 2019 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-30655946

RESUMEN

The further optimization of ER-α degradation efficacy of a series of ER modulators by refining side-chain substitution led to efficacious selective estrogen receptor degraders (SERDs). A fluoromethyl azetidine group was found to be preferred and resulted in the identification of bis-phenol chromene 17ha. In a tamoxifen-resistant breast cancer xenograft model, 17ha (ER-α degradation efficacy = 97%) demonstrated tumor regression, together with robust reduction of intratumoral ER-α levels. However, despite superior oral exposure, 5a (ER-α degradation efficacy = 91%) had inferior activity. This result suggests that optimizing ER-α degradation efficacy leads to compounds with robust effects in a model of tamoxifen-resistant breast cancer. Compound 17ha (GDC-0927) was evaluated in clinical trials in women with metastatic estrogen receptor-positive breast cancer.

17.
Bioorg Med Chem Lett ; 29(3): 367-372, 2019 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-30587451

RESUMEN

Potent estrogen receptor ligands typically contain a phenolic hydrogen-bond donor. The indazole of the selective estrogen receptor degrader (SERD) ARN-810 is believed to mimic this. Disclosed herein is the discovery of ARN-810 analogs which lack this hydrogen-bond donor. These SERDs induced tumor regression in a tamoxifen-resistant breast cancer xenograft, demonstrating that the indazole NH is not necessary for robust ER-modulation and anti-tumor activity.


Asunto(s)
Antineoplásicos/farmacología , Cinamatos/farmacología , Resistencia a Antineoplásicos/efectos de los fármacos , Indazoles/farmacología , Receptores de Estrógenos/antagonistas & inhibidores , Moduladores Selectivos de los Receptores de Estrógeno/farmacología , Tamoxifeno/farmacología , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Cinamatos/síntesis química , Cinamatos/química , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Indazoles/síntesis química , Indazoles/química , Neoplasias Mamarias Experimentales/tratamiento farmacológico , Neoplasias Mamarias Experimentales/metabolismo , Neoplasias Mamarias Experimentales/patología , Ratones , Estructura Molecular , Receptores de Estrógenos/metabolismo , Moduladores Selectivos de los Receptores de Estrógeno/síntesis química , Moduladores Selectivos de los Receptores de Estrógeno/química , Relación Estructura-Actividad , Tamoxifeno/síntesis química , Tamoxifeno/química
18.
J Med Chem ; 61(17): 7917-7928, 2018 09 13.
Artículo en Inglés | MEDLINE | ID: mdl-30086626

RESUMEN

About 75% of breast cancers are estrogen receptor alpha (ER-α) positive, and women typically initially respond well to antihormonal therapies such as tamoxifen and aromatase inhibitors, but resistance often emerges. Fulvestrant is a steroid-based, selective estrogen receptor degrader (SERD) that both antagonizes and degrades ER-α and shows some activity in patients who have progressed on antihormonal agents. However, fulvestrant must be administered by intramuscular injections that limit its efficacy. We describe the optimization of ER-α degradation efficacy of a chromene series of ER modulators resulting in highly potent and efficacious SERDs such as 14n. When examined in a xenograft model of tamoxifen-resistant breast cancer, 14n (ER-α degradation efficacy = 91%) demonstrated robust activity, while, despite superior oral exposure, 15g (ER-α degradation efficacy = 82%) was essentially inactive. This result suggests that optimizing ER-α degradation efficacy in the MCF-7 cell line leads to compounds with robust effects in models of tamoxifen-resistant breast cancer derived from an MCF-7 background.


Asunto(s)
Antineoplásicos/administración & dosificación , Benzopiranos/química , Neoplasias de la Mama/tratamiento farmacológico , Proliferación Celular/efectos de los fármacos , Receptor alfa de Estrógeno/metabolismo , Moduladores Selectivos de los Receptores de Estrógeno/administración & dosificación , Administración Oral , Animales , Antineoplásicos/química , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Resistencia a Antineoplásicos/efectos de los fármacos , Femenino , Humanos , Ratones , Ratas , Moduladores Selectivos de los Receptores de Estrógeno/química , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto
19.
Med Sci Monit ; 24: 4288-4294, 2018 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-29932168

RESUMEN

BACKGROUND Thrombophilic gene polymorphism is known to be a risk factor for recurrent pregnancy loss (RPL), but few studies have confirmed a possible role of thrombophilic genes polymorphism in RPL risk. This study was conducted to understand the relationship of the mutations of some thrombophilia-associated gene polymorphism (heterozygous/homozygous) with RPL. We compared patients with 2 abortions to patients with 3 or more abortions among Turkish women. MATERIAL AND METHODS In this study, patients previously diagnosed with habitual abortus at Obstetrics and Gynecology outpatient clinics in Turkey between 2012 and 2016 were included. In their peripheral blood, we detected factor V Leiden H1299R, prothrombin G20210A, MTHFR C677T, MTHFR A1298C, PAI-1 4G/5G, and PAI-1 4G/4G gene mutations. RESULTS In this study, we have observed statistically meaningful data (P<0.01) related to the relationship between RPL and thrombophilia-associated gene polymorphisms such as heterozygous factor V Leiden H1299R, heterozygous prothrombin G20210A, PAI-1 4G/5G, and PAI-1 4G/4G. CONCLUSIONS We found that diagnosis of thrombophilic genes polymorphism is useful to determine the causes of RPL, recognizing that this multifactorial disease can also be influenced by various acquired factors, including reproduction-associated risk factors and prolonged immobilization.


Asunto(s)
Aborto Habitual/etiología , Trombofilia/complicaciones , Aborto Habitual/genética , Adulto , Demografía , Femenino , Humanos , Mutación/genética , Embarazo , Adulto Joven
20.
Med Sci Monit ; 24: 58-66, 2018 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-29298972

RESUMEN

BACKGROUND In the present study we retrospectively evaluated the results of outpatients who had an HPV analysis, and present objective evidence for the administration of preventive inoculation in our area. MATERIAL AND METHODS We retrospectively reviewed 532 outpatients who visited a single center between 2012 and 2016 and had an HPV infection analysis. The criteria for inclusion of patients with unhealthy cervix in the study were: erosion, chronic cervicitis, healed lacerations, hypertrophied cervix, and abnormal discharges from the cervix. RESULTS We found that 122 out of 532 patients were infected with HPV, and the rate of multiple infections was 59.0% (72/122). HR-HPV (group 1 carcinogens HPV-16 (18.9%, 23/122), HPV-18 (13.1%, 16/122), HPV- 31 (4.9%, 6/122), HPV-33 (3.3%, 4/122), HPV-35 (7.4.9%/122), HPV-39 (5.7%, 7/122), HPV-45 (5.7%, 7/122), HPV-51 (11.5%, 15/122); Group 3 LR-HPV; HPV-6 (31.1%, 38/122), HPV-11 (26.2%, 32/122), HPV-42 (9.0%, 11/122) and HPV-43 (4.9%, 6/122). In terms of linear-by-linear association test, no significant statistical difference was identified between years. The P value for HPV infection rate on year basis was P>0.05. CONCLUSIONS In this hospital-based retrospective analysis, HPV types were found to be similar to HPV types reported in developed countries. We firmly suggest that patients should be informed about the risk of HPV infection at early ages.


Asunto(s)
Papillomaviridae/genética , Infecciones por Papillomavirus/epidemiología , Adulto , Cuello del Útero/virología , Femenino , Genotipo , Humanos , Persona de Mediana Edad , Infecciones por Papillomavirus/diagnóstico , Proyectos Piloto , Prevalencia , Estudios Retrospectivos , Clase Social , Turquía/epidemiología , Frotis Vaginal/métodos , Adulto Joven
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