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1.
J Formos Med Assoc ; 123(4): 487-495, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37852875

RESUMEN

OBJECTIVE: The approved standard dose of pembrolizumab (200 mg administrated every 3 weeks) for cancer treatment imposes a significant financial burden on patients. However, no study has analyzed the clinical outcomes of low-dose pembrolizumab among individuals diagnosed with gynecologic cancer. The primary objective of this study was to assess the effectiveness and safety of a low-dose pembrolizumab regimen in real-world clinical practice. METHODS: We retrospectively assessed the efficacy and safety data of patients with gynecologic malignancies who received pembrolizumab between 2017 and 2022 at Kaohsiung Chang Gung Memorial Hospital. Furthermore, we conducted a comparative analysis of the objective response rate (ORR) and progression-free survival (PFS) between patients with deficient mismatch repair (dMMR) and proficient MMR (pMMR). RESULTS: A total of thirty-nine patients were included and received pembrolizumab at fixed dosages of 50 mg (5.1%), 100 mg (84.6%) and 200 mg (10.3%) per cycle. Compared to the pMMR group, the dMMR group exhibited a tendency toward improved ORR (45.5% vs. 13.0%, p = 0.074), and notably, the median duration of response remained unreached. There was no significant difference in PFS between the dMMR and pMMR groups; however, the patients with dMMR in tumor tissue had a trend of better survival (p = 0.079). Incidence of immune-related adverse events (irAEs) of any grade was observed in 13 patients (33.3%), with 3 individuals (7.7%) experiencing grade 3 or 4 events. CONCLUSION: Low-dose pembrolizumab may be a cost-effective and safe treatment option without compromising clinical outcomes in patients with refractory gynecologic cancers.


Asunto(s)
Neoplasias de los Genitales Femeninos , Humanos , Femenino , Neoplasias de los Genitales Femeninos/tratamiento farmacológico , Neoplasias de los Genitales Femeninos/genética , Neoplasias de los Genitales Femeninos/inducido químicamente , Estudios Retrospectivos , Anticuerpos Monoclonales Humanizados/efectos adversos , Supervivencia sin Progresión
2.
BMC Cancer ; 23(1): 871, 2023 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-37715113

RESUMEN

BACKGROUND: While the treatment guidelines have been established for pure urothelial carcinoma (pUC), patients with variant type urothelial carcinoma (vUC) face limited effective treatment options. The effectiveness of immune checkpoint inhibitors (ICI) in patients with vUC remains uncertain and necessitates additional research. METHOD: We conducted a retrospective, multicenter study to explore the effectiveness of ICI in patients with pUC or vUC in Taiwan. We evaluated the overall response rate (ORR) through univariate logistic regression analysis and examined the overall survival (OS) and progression-free survival (PFS) using Kaplan-Meier analysis. Additionally, we employed univariate and multivariate Cox proportional hazards models to analyze the data. RESULT: A total of 142 patients (116 pUC, 26 vUC) were included in our final analysis. The ORR was marginally higher in patients with pUC compared to those with vUC (34.5% vs. 23.1%, p = 0.26). Among all patients, 12.9% with pUC achieved a complete response (CR) after ICI treatment, while no vUC cases achieved CR (p = 0.05). There were no significant differences in PFS (median 3.6 months vs. 4.1 months, p = 0.34) or OS (median 16.3 months vs. 11.0 months, p = 0.24) when comparing patients with pUC or vUC. In the subgroup analysis, patients with pUC who underwent first-line ICI treatment exhibited significantly improved OS compared to those with vUC (24.6 months vs. 9.1 months, p = 0.004). CONCLUSION: The use of ICI as monotherapy is a feasible and effective treatment approach for patients with metastatic vUC.


Asunto(s)
Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Humanos , Carcinoma de Células Transicionales/tratamiento farmacológico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Pronóstico , Estudios Retrospectivos
3.
Sens Actuators B Chem ; 357: 131415, 2022 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-35043033

RESUMEN

Facing the unstopped surges of COVID-19, an insufficient capacity of diagnostic testing jeopardizes the control of disease spread. Due to a centralized setting and a long turnaround, real-time reverse transcription polymerase chain reaction (real-time RT-PCR), the gold standard of viral detection, has fallen short in timely reflecting the epidemic status quo during an urgent outbreak. As such, a rapid screening tool is necessitated to help contain the spread of COVID-19 amid the countries where the vaccine implementations have not been widely deployed. In this work, we propose a saliva-based COVID-19 antigen test using the electrical double layer (EDL)-gated field-effect transistor-based biosensor (BioFET). The detection of SARS-CoV-2 nucleocapsid (N) protein is validated with limits of detection (LoDs) of 0.34 ng/mL (7.44 pM) and 0.14 ng/mL (2.96 pM) in 1× PBS and artificial saliva, respectively. The specificity is inspected with types of antigens, exhibiting low cross-reactivity among MERS-CoV, Influenza A virus, and Influenza B virus. This portable system is embedded with Bluetooth communication and user-friendly interfaces that are fully compatible with digital health, feasibly leading to an on-site turnaround, an effective management, and a proactive response taken by medical providers and frontline health workers.

4.
Sensors (Basel) ; 22(6)2022 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-35336407

RESUMEN

In this paper, an analytical solution for a clamped-edge bimorph disk-type piezoelectric transformer with Kirchhoff thin plate theory is proposed. The electromechanical equations for transient motions are first derived, and coupled expressions for mechanical response and voltage output are obtained. For the case of excitation around the first resonant frequency, the resulting equations are further simplified. There are analytical solutions for a mechanical response, voltage, current, and power outputs. According to the analytical model, the output voltage is affected by the inner radius of the input and output electrodes, the radius of the piezoelectric transformer (PT), and the thickness ratio between the lead zirconate titanate (PZT) layer and the substrate. When the inner radius of the input electrode approaches zero (electrode becomes circular shape), it achieves maximum output voltage at the first resonance frequency excitation. On the contrary, when the inner radius of the output electrode approaches zero, the output voltage reaches its minimum value. Voltage ratios remain constant as the disk radius changes, and the first resonance frequency is inversely proportional to the square of the disk radius. The voltage ratio is fixed even with the miniaturization of the PT.

5.
Molecules ; 27(7)2022 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-35408536

RESUMEN

Michelia formosana (Kanehira) Masamune is a broad-leaved species widespread in East Asia; the wood extract and its constituents possess antifungal activity against wood-decay fungi. Antifungal activities of leaf essential oil and its constituents from M. formosana were investigated in the present study. Bioassay-guided isolation was applied to isolate the phytochemicals from leaf essential oil. 1D and 2D NMR, FTIR, and MS spectroscopic analyses were applied to elucidate the chemical structures of isolated compounds. Leaf essential oil displayed antifungal activity against wood decay fungi and was further separated into 11 fractions by column chromatography. Four sesquiterpenoids were isolated and identified from the active fractions of leaf essential oil through bioassay-guided isolation. Among these sesquiterpenoids, guaiol, bulnesol, and ß-elemol have higher antifungal activity against brown-rot fungus Laetiporus sulphureus and white-rot fungus Lenzites betulina. Leaf essential oil and active compounds showed better antifungal activity against L. sulphureus than against L. betulina. The molecular structure of active sesquiterpenoids all contain the hydroxyisopropyl group. Antifungal sesquiterpenoids from M. formosana leaf essential oil show potential as natural fungicides for decay control of lignocellulosic materials.


Asunto(s)
Magnolia , Aceites Volátiles , Sesquiterpenos , Antifúngicos/química , Hongos , Aceites Volátiles/química , Hojas de la Planta/química , Sesquiterpenos/análisis , Sesquiterpenos/farmacología , Madera/microbiología
6.
Oncology ; 98(3): 146-153, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31794969

RESUMEN

OBJECTIVES: Platinum-based chemotherapy is the standard treatment for metastatic urothelial carcinoma (mUC). However, considering elderly patients often experience comorbidities and frailty, the utility of cisplatin-based chemotherapy for elderly patients is still debatable. We conducted this study to compare the safety and efficacy of carboplatin and cisplatin in elderly patients with mUC. METHODS: This retrospective study enrolled elderly patients with mUC (defined as aged ≥70 years) who underwent first-line platinum-based chemotherapy between September 2001 and October 2018. The primary endpoints were chemotherapy-related adverse events (AEs), including treatment-related hospitalization or death. The secondary outcomes were overall survival (OS) and progression-free survival calculated by Kaplan-Meier analysis. RESULTS: In total, 108 elderly patients with mUC were enrolled and allocated into the cisplatin or carboplatin group. Patients treated with carboplatin-based chemotherapy had a significantly higher incidence of all grade ≥3 AEs (78.8 vs. 50.0%, p = 0.008) than those on cisplatin. AE-related hospitalization (47.5 vs. 19.1%, p = 0.002) and treatment-related death (17.5 vs. 4.4%, p = 0.02) were significantly increased in the carboplatin group. In the univariate analysis, the median OS in the cisplatin group was significantly increased compared with the carboplatin group (13.6 vs. 7.2 months, p = 0.045). The Cox multivariate regression model indicated that leukocytosis (HR 3.17, 95% CI 1.84-5.46, p < 0.001) and anemia (HR 2.02, 95% CI 1.11-3.65, p = 0.02) were independent prognostic factors. CONCLUSION: Elderly patients with mUC treated with cisplatin-based chemotherapy had better survival and safety profiles than those treated with carboplatin. Age itself was not a crucial factor in determining cisplatin eligibility.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carboplatino/administración & dosificación , Carcinoma/tratamiento farmacológico , Cisplatino/administración & dosificación , Neoplasias Urológicas/tratamiento farmacológico , Urotelio/efectos de los fármacos , Factores de Edad , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carboplatino/efectos adversos , Carcinoma/mortalidad , Carcinoma/secundario , Cisplatino/efectos adversos , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Supervivencia sin Progresión , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Neoplasias Urológicas/mortalidad , Neoplasias Urológicas/patología , Urotelio/patología
7.
Sensors (Basel) ; 21(1)2020 Dec 30.
Artículo en Inglés | MEDLINE | ID: mdl-33396872

RESUMEN

In this paper, a piezoelectric wave-energy converter (PWEC), consisting of a buoy, a frequency up-conversion mechanism, and a piezoelectric power-generator component, is developed. The frequency up-conversion mechanism consists of a gear train and geared-linkage mechanism, which converted lower frequencies of wave motion into higher frequencies of mechanical motion. The slider had a six-period displacement compared to the wave motion and was used to excite the piezoelectric power-generation component. Therefore, the operating frequency of the piezoelectric power-generation component was six times the frequency of the wave motion. The developed, flexible piezoelectric composite films of the generator component were used to generate electrical voltage. The piezoelectric film was composed of a copper/nickel foil as the substrate, lead-zirconium-titanium (PZT) material as the piezoelectric layer, and silver material as an upper-electrode layer. The sol-gel process was used to fabricate the PZT layer. The developed PWEC was tested in the wave flume at the Tainan Hydraulics Laboratory, Taiwan (THL). The maximum height and the minimum period were set to 100 mm and 1 s, respectively. The maximum voltage of the measured value was 2.8 V. The root-mean-square (RMS) voltage was 824 mV, which was measured through connection to an external 495 kΩ resistive load. The average electric power was 1.37 µW.

8.
Fish Shellfish Immunol ; 62: 41-46, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28089894

RESUMEN

Several proteomic techniques were used to determine the cleavage site of the mature antimicrobial peptide of Nile tilapia ß-defensin. The computer-predicted Nile tilapia ß-defensin (25ASFPWSCLSLSGVCRKVCLPTELFFGPLGCGKGSLCCVSHFL66) composed of 42 amino acids was chemically synthesized and prepared to produce an antibody for Western blotting. Total proteins from the skin of the Nile tilapia were separated on two-dimensional electrophoresis, and the spot of Nile tilapia ß-defensin was recognized using Western blot analysis. It was then excised and extracted from the gel. The precise molecular mass of this spot was determined by LC-MS/MS spectrometry. Four major peptides were discovered, with molecular weights of 4293.2 Da, 4306.5 Da, 4678.9 Da, and 4715.0 Da. The calculated mass of the 40-amino-acid sequence (27FPWSCLSLSGVCRKVCLPTELFFGPLGCGKGSLCCVSHFL66) of Nile tilapia ß-defensin starting from Phe27 and ending with Leu66 was 4293.18 Da, which completely matched the 4293.2 Da peptide that was obtained from the mass spectrometry analysis. This result confirmed that the cleavage site for the mature C-terminal Nile tilapia ß-defensin is at residue Ser26-Phe27, not at Ala24-25 as predicted by computer analysis. This study provides a simple but reliable model to determine the cleavage site for a mature antimicrobial peptide.


Asunto(s)
Péptidos Catiónicos Antimicrobianos/genética , Cíclidos/genética , Proteínas de Peces/genética , beta-Defensinas/genética , Secuencia de Aminoácidos , Animales , Péptidos Catiónicos Antimicrobianos/química , Péptidos Catiónicos Antimicrobianos/metabolismo , Fenómenos Fisiológicos Bacterianos , Western Blotting/veterinaria , Cromatografía Liquida/veterinaria , Cíclidos/inmunología , Electroforesis en Gel Bidimensional/veterinaria , Proteínas de Peces/química , Proteínas de Peces/metabolismo , Proteómica , Alineación de Secuencia/veterinaria , Espectrometría de Masas en Tándem/veterinaria , beta-Defensinas/química , beta-Defensinas/metabolismo
10.
Sensors (Basel) ; 14(11): 22099-112, 2014 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-25421736

RESUMEN

In this study, we develop a clamped-clamped beam-type piezoelectric vacuum pressure sensing element. The clamped-clamped piezoelectric beam is composed of a PZT layer and a copper substrate. A pair of electrodes is set near each end. An input voltage is applied to a pair of electrodes to vibrate the piezoelectric beam, and the output voltage is measured at the other pair. Because the viscous forces on the piezoelectric beam vary at different air pressures, the vibration of the beam depends on the vacuum pressure. The developed pressure sensor can sense a wide range of pressure, from 6.5 × 10(-6) to 760 Torr. The experimental results showed that the output voltage is inversely proportional to the gas damping ratio, and thus, the vacuum pressure was estimated from the output voltage.

11.
Int J Mol Sci ; 15(6): 10926-35, 2014 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-24941253

RESUMEN

Phytochemical investigation of the heartwood of Michelia compressa afforded forty-four compounds, which were identified by comparison of experimental and literature analytical and spectroscopic data. Some compounds were evaluated for their anti-inflammatory and anticancer bioactivities. The result showed that soemerine (1) and cyathisterol (2) exhibited significant nitric oxide (NO) inhibition, with IC50 values of 8.5±0.3 and 9.6±0.5 µg/mL, respectively. In addition, liriodenine (3) and oliveroline (4) exhibited cytotoxicity to human nasopharyngeal carcinoma (NPC-TW01), non-small cell lung carcinoma (NCI-H226), T cell leukemia (Jurkat), renal carcinoma (A498), lung carcinoma (A549) and fibrosarcoma (HT1080) cell lines with IC50 values in the range of 15.7-3.68 µM.


Asunto(s)
Antiinflamatorios/química , Antineoplásicos/química , Aporfinas/química , Magnoliaceae/química , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/farmacología , Antineoplásicos/aislamiento & purificación , Antineoplásicos/farmacología , Antineoplásicos/toxicidad , Aporfinas/aislamiento & purificación , Aporfinas/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Células Jurkat , Magnoliaceae/metabolismo , Óxido Nítrico/metabolismo , Extractos Vegetales/química , Extractos Vegetales/farmacología
12.
Cancer Med ; 13(2): e7008, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38334504

RESUMEN

BACKGROUND: Studies on the correlation between high body mass index (BMI) and extended survival among patients receiving immune checkpoint inhibitors (ICIs) have been made, although findings have shown variability. Our research explored the phenomenon of the "obesity paradox" in patients with metastatic urothelial carcinoma (mUC) undergoing treatment with ICIs. MATERIALS AND METHODS: We conducted a retrospective analysis of patients diagnosed with mUC who received a minimum of one cycle of ICI treatment at two medical centers in Taiwan from September 2015 to January 2023. Features of patients' clinicopathologic factors, including age, sex, primary or metastatic location, treatment line, and BMI were examined. The primary outcome were overall survival (OS) and progression-free survival (PFS), which were assessed utilizing the Kaplan-Meier method. We employed the Cox-regression model to adjust for multiple covariates. RESULTS: A total of 215 patients were included, with 128 (59.5%) being male, and the median age was 70 years. In the obese group (BMI ≥25 kg/m2 ), patients demonstrated significantly better median OS compared to the non-obese group (BMI <25 kg/m2 ) (21.9 vs. 8.3 months; p = 0.021). However, there was no significant difference in median PFS between the high and low BMI groups (4.7 vs. 2.8 months; p = 0.16). Post-hoc subgroup revealed a survival benefit from ICI treatment in male patients within the BMI ≥25 kg/m2 group (HR 0.49, 95% CI 0.30-0.81, p = 0.005). CONCLUSION: Based on real-world data from the Asia-Pacific region, there appears to be a correlation between obesity and prolonged OS in patients receiving ICI treatment for mUC.


Asunto(s)
Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Humanos , Masculino , Anciano , Femenino , Índice de Masa Corporal , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Estudios Retrospectivos , Obesidad/complicaciones , Obesidad/epidemiología
13.
Am J Cancer Res ; 13(3): 1004-1025, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37034220

RESUMEN

Head and neck squamous carcinoma (HNSCC) affects more than half a million individuals and ranks the ninth leading cause of death globally each year. Many patients develop treatment resistance leading to poor clinical outcomes. The poor treatment responses are in part due to the heterogeneity of HNSCC tumor and tumor microenvironment (TME). The interaction of tumor cells with their TME has been studied vigorously in recent years because of their pivotal roles in tumorigenesis and determining the treatment response. Cancer-associated fibroblasts (CAFs) are one of the most abundant tumor-infiltrating cells, which have been shown to associate with the aggressive behavior of HNSCC. Hence, targeting and disrupting the tumor-CAFs interactions represents a rational therapeutic approach. To develop targeted therapeutic drugs against CAFs, the identification of CAF-associated gene signature is essential. Here, we analyzed multiple sequencing databases including microarrays and single-cell RNA-sequencing databases and identified SPARC/MMP9/CD44 as HNSCC targetable gene signatures encompassing cancer-associated fibroblasts (CAFs). We found SPARC/MMP9CD44 signature was highly expressed in HNSC tissues compared to adjacent normal tissues. Increased SPARC/MMP9/CD44 signature levels strongly correlated with tumor-infiltrating CAFs, suggesting the functional importance of this signature for HNSCC-CAFs interaction and progression. Subsequently, we utilized a genomics approach and identified midostaurin as the top-ranking drug candidate for targeting SPARC/MMP9/CD44 signature. For validation, we performed molecular docking of midostaurin in complex with SPARC/MMP9/CD44 and demonstrated midostaurin's high binding affinities compared to their respective standard inhibitors. In summary, our study provided a rapid genomics approach for identifying targetable gene signature and drug candidate for HNSCC.

14.
Cells ; 12(11)2023 05 25.
Artículo en Inglés | MEDLINE | ID: mdl-37296592

RESUMEN

Urothelial carcinoma (UC) is characterized by a high incidence of TP53 mutation, and overcoming resistance to cisplatin-based chemotherapy in UC is a major concern. Wee1 is a G2/M phase regulator that controls the DNA damage response to chemotherapy in TP53-mutant cancers. The combination of Wee1 blockade with cisplatin has shown synergistic efficacy in several types of cancers, but little is known regarding UC. The antitumor efficacy of the Wee1 inhibitor (AZD-1775) alone or in combination with cisplatin was evaluated in UC cell lines and a xenograft mouse model. AZD-1775 enhanced the anticancer activity of cisplatin by increasing cellular apoptosis. AZD-1775 inhibited the G2/M checkpoint, improving the sensitivity of mutant TP53 UC cells to cisplatin by enhancing the DNA damage process. We confirmed that AZD-1775 combined with cisplatin reduced tumor volume and proliferation activity and increased the markers of cell apoptosis and DNA damage in the mouse xenograft model. In summary, the Wee1 inhibitor AZD-1775 combined with cisplatin elicited a promising anticancer efficacy in UC, and constitutes an innovative and promising therapeutic strategy.


Asunto(s)
Antineoplásicos , Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Humanos , Animales , Ratones , Cisplatino/farmacología , Cisplatino/uso terapéutico , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Carcinoma de Células Transicionales/tratamiento farmacológico , Proteínas de Ciclo Celular/metabolismo , Proteínas Tirosina Quinasas/metabolismo , Línea Celular Tumoral , Daño del ADN
15.
Sensors (Basel) ; 12(3): 2710-28, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22736973

RESUMEN

We coupled 16S rDNA PCR and DNA hybridization technology to construct a microarray for simultaneous detection and discrimination of eight fish pathogens (Aeromonas hydrophila, Edwardsiella tarda, Flavobacterium columnare, Lactococcus garvieae, Photobacterium damselae, Pseudomonas anguilliseptica, Streptococcus iniae and Vibrio anguillarum) commonly encountered in aquaculture. The array comprised short oligonucleotide probes (30 mer) complementary to the polymorphic regions of 16S rRNA genes for the target pathogens. Targets annealed to the microarray probes were reacted with streptavidin-conjugated alkaline phosphatase and nitro blue tetrazolium/5-bromo-4-chloro-3'-indolylphosphate, p-toluidine salt (NBT/BCIP), resulting in blue spots that are easily visualized by the naked eye. Testing was performed against a total of 168 bacterial strains, i.e., 26 representative collection strains, 81 isolates of target fish pathogens, and 61 ecologically or phylogenetically related strains. The results showed that each probe consistently identified its corresponding target strain with 100% specificity. The detection limit of the microarray was estimated to be in the range of 1 pg for genomic DNA and 10(3) CFU/mL for pure pathogen cultures. These high specificity and sensitivity results demonstrate the feasibility of using DNA microarrays in the diagnostic detection of fish pathogens.


Asunto(s)
Bacterias/genética , Colorimetría , Análisis de Secuencia por Matrices de Oligonucleótidos , ARN Ribosómico 16S/análisis , Fosfatasa Alcalina/química , Fosfatasa Alcalina/metabolismo , Animales , Bacterias/aislamiento & purificación , Cartilla de ADN/metabolismo , Sondas de ADN/metabolismo , Enfermedades de los Peces/diagnóstico , Enfermedades de los Peces/microbiología , Peces/microbiología , Genoma Bacteriano , Hibridación de Ácido Nucleico , Reacción en Cadena de la Polimerasa , Estreptavidina/química , Sales de Tetrazolio/química
16.
Front Bioeng Biotechnol ; 10: 853947, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35372290

RESUMEN

Amyloid-ß(1-42) [Aß(1-42)] oligomer accumulations are associated with physiologic alterations in the brains of individuals with Alzheimer's disease. In this study, we demonstrate that a nanostructured gold electrode with deposited gold nanoparticles, induced via electrochemical impedance spectroscopy (EIS), may be used as an Aß(1-42) conformation biosensor for the detection of Alzheimer's disease. Monoclonal antibodies (12F4) were immobilized on self-assembled monolayers of the electrochemical sandwich immunoassay biosensor to capture Aß(1-42) monomers and oligomers. Western blot and fluorescence microscopy analyses were performed to confirm the presence of Aß(1-42) monomers and oligomers. EIS analysis with an equivalent circuit model was used to determine the concentrations of different Aß(1-42) conformations in this study. We identified conformations of Aß(1-42) monomers and Aß(1-42) oligomers using probe antibodies (12F4) by employing EIS. R Aß ( 1 - 42 ) indicates the sum resistance of impedance measured during Aß(1-42) immobilization. Δ R 12 F 4 refers to the concentration of probe antibody (12F4) binding with Aß(1-42). The concentration of Aß(1-42) oligomer was defined as the percentage of Aß(1-42) aggregation R 12 F 4 / R Aß ( 1 - 42 ) . The experimental results show that the biosensor has high selectivity to differentiate Aß(1-40) and Aß(1-42) monomers and Aß(1-42) oligomers and that it can detect Aß(1-42) oligomer accurately. The linear detection range for Aß(1-42) oligomers was between 10 pg/ml and 100 ng/ml. The limit of detection was estimated to be 113 fg/ml.

17.
J Immunother ; 45(9): 407-414, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36121316

RESUMEN

Immune checkpoint inhibitors (ICIs) are widely used for first-line cisplatin-ineligible patients with metastatic urothelial carcinoma (mUC). However, whether to use ICIs as monotherapy or in combination with chemotherapy is still uncertain. We retrospectively analyzed cisplatin-ineligible patients with mUC who underwent first-line ICI monotherapy or ICI plus chemotherapy at 2 medical centers in Taiwan from 2016 to 2021. We calculated the objective response rate, progression-free survival, and overall survival (OS) using the Kaplan-Meier method and Cox regression model for multivariable analysis. In total, 130 patients were enrolled and categorized into 2 groups: an ICI monotherapy group [immunotherapy (IO), n=101] and an ICI plus noncisplatin chemotherapy group [immunotherapy and chemotherapy (IC), n=29]. The median OS of patients in the IO and IC groups was 19.5 and 9.7 months ( P =0.33). Among patients with high programmed cell death ligand-1-expressing tumors, the median OS was significantly prolonged in the IO group compared with the IC group (not reached vs. 6.3 mo, P =0.02). First-line ICI monotherapy demonstrated robust antitumor activity in cisplatin-ineligible patients with mUC. Combining noncisplatin chemotherapy with ICI did not improve clinical outcomes.


Asunto(s)
Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Neoplasias Urológicas , Carcinoma de Células Transicionales/tratamiento farmacológico , Carcinoma de Células Transicionales/patología , Cisplatino/uso terapéutico , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Factores Inmunológicos/uso terapéutico , Ligandos , Estudios Retrospectivos , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias Urológicas/tratamiento farmacológico
18.
Talanta ; 236: 122886, 2022 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-34635266

RESUMEN

Rheumatoid arthritis (RA), an autoimmune and chronic inflammatory disorder, is an incurable disease. We developed a peptide-based electrochemical sensor using electrochemical impedance spectroscopy that can be used to detect autoantibodies for RA diagnostics. We first validated that the developed peptide showed high sensitivity and could compliment the current gold standard method of an anti-cyclic citrullinated peptide antibody (anti-CCP) ELISA. The developed peptide can be modified on the nanogold surface of the working electrode of sensing chips through the method of a self-assembling monolayer. The sensing process was first optimized using a positive control cohort and a healthy control cohort. Subsequently, 10 clinically confirmed samples from RA patients and five healthy control samples were used to find the threshold value of the impedance between RA and healthy subjects. Furthermore, 10 clinically confirmed samples but with low values of anti-CCP autoantibodies were used to evaluate the sensitivity of the present method compared to the conventional method. The proposed method showed better sensitivity than the current conventional anti-CCP ELISA method.


Asunto(s)
Artritis Reumatoide , Artritis Reumatoide/diagnóstico , Espectroscopía Dieléctrica , Impedancia Eléctrica , Ensayo de Inmunoadsorción Enzimática , Humanos , Péptidos
19.
J Nurs Res ; 29(3): e152, 2021 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-33840769

RESUMEN

BACKGROUND: Hand massage therapies have been used to relieve anxiety and pain in various clinical situations. The effects of machine-based hand massage on preoperative anxiety in ambulatory surgery settings have not been evaluated. PURPOSE: This prospective study was designed to investigate the effect of machine-based hand massage on preoperative anxiety and vital signs in ambulatory surgery patients. METHODS: One hundred ninety-nine patients aged 18 years and older who were scheduled to receive ambulatory surgery were recruited from the Taipei Municipal Wanfang Hospital in Taipei City, Taiwan. The patients were assigned randomly to the experimental group (n = 101), which received presurgical machine-based hand massage therapy, and the control group (n = 98), which received no intervention. The patients in both groups completed the Spielberger State-Trait Anxiety Inventory short form at preintervention (baseline) and postintervention. RESULTS: Within-group comparisons of Spielberger State-Trait Anxiety Inventory short form scores showed significant decreases between preintervention and postintervention scores in the experimental group (44.3 ± 11.2 to 37.9 ± 8.7) and no significant change in the control group. Within-group comparisons of vital signs revealed a significant increase in mean respiration rate between baseline and postintervention in both groups (both ps < .05). Blood pressure was found to have decreased significantly only in the control group at postintervention (p < .05). No significant preintervention to postintervention change in pulse was observed in either group. CONCLUSIONS: The findings of this study indicate that machine-based hand massage reduces anxiety significantly in patients awaiting ambulatory surgery while not significantly affecting their vital signs.


Asunto(s)
Procedimientos Quirúrgicos Ambulatorios , Ansiedad , Mano , Ansiedad/prevención & control , Humanos , Masaje , Estudios Prospectivos
20.
Cancers (Basel) ; 13(20)2021 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-34680230

RESUMEN

(1) Background: To investigate the prognostic value of cancer-inflammation prognostic index (CIPI) in patients with metastatic colorectal cancer (mCRC) on regorafenib treatment; (2) Methods: Patients with mCRC who were given regorafenib as later-line treatment at Kaohsiung and Linkou Chang-Gung Memorial Hospital between November 2014 and January 2021 were consecutively enrolled. All relevant clinicopathologic, laboratory data and survival status were recorded. Independent prognostic factors were determined by the multivariate Cox regression method; (3) Results: In total, 106 patients in the training cohort and 250 in the validation cohort were enrolled. The median OS for patients with CIPI ≥ 300 and < 300 in the training cohort was 3.8 and 9.0 months, respectively (hazard ratio (HR) 2.78, 95% confidence interval (CI) 1.82-4.23; p < 0.0001). Time to regorafenib, liver metastasis and CIPI were independent factors by multivariate Cox regression analyses. A new scoring model demonstrated a good discriminatory ability to risk stratification of a patient's survival; (4) Conclusions: We identified CIPI as a novel serum marker highly associated with overall survival in patients with mCRC receiving regorafenib treatment. Further confirmatory studies are warranted.

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