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1.
Support Care Cancer ; 30(7): 6225-6232, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35449368

RESUMEN

OBJECTIVE: A prospective randomized controlled trial was conducted to compare 5 mg olanzapine plus standard triple antiemetic therapy for the prevention of nausea and vomiting induced by multiple-day cisplatin chemotherapy. METHODS: Patients who received a 3-day cisplatin-based chemotherapy (25 mg/m2/d) were given either 5 mg olanzapine plus triple therapy with aprepitant, tropisetron, and dexamethasone (quadruple group) or 5 mg olanzapine plus tropisetron and dexamethasone, omitting aprepitant (triplet group). The primary endpoint was the complete response (CR) in the overall phase (OP) (0-120 h) between quadruple group and triplet group. The secondary endpoints were the CR in the acute phase (AP) (0-24 h) and delayed phase (DP) (25-120 h) between two groups. The first time of vomiting was also compared by Kaplan-Meier curves. The impact of chemotherapy-induced nausea and vomiting (CINV) on the quality of life was assessed by the Functional Living Index-Emesis (FLIE). Aprepitant-related adverse effects (AEs) were also recorded. RESULTS: (1) The primary endpoint CR during OP was 76.0% (45/59) vs 67.0% (41/61) between the quadruple group and triplet group (P = 0.271). The secondary endpoint CR during the AP was significantly higher in the quadruple group than in the triplet group, which was 100.0% (59/59) vs 93.0% (57/61) (P = 0.045). The difference of CR during delayed phase between the groups was especially higher in the quadruple group compared to the triplet group (76.0% (45/59) vs 67.0% (41/61) (P = 0.271)). The rate of patients who achieved total protection in the overall phase was also higher in the quadruple group than the triplet group (28.8% (17/59) vs 23.0% (14/61) (P = 0.463)). During the OP, the incidence of no vomiting in the quadruple group and the triplet group was 93.2% (55/59) vs 80.3% (49/61) (P = 0.038), respectively. (2) Kaplan-Meier curves of time to first emesis were obviously longer in the quadruple group compared with the triplet group (P = 0.031). According to FLIE, no impact of CINV on daily life was defined as total score of questionnaire > 108; this study exhibited identical life quality between two groups. (3) The most common aprepitant- or olanzapine-related AEs included sedation, fatigue, and constipation. The occurrences between two groups were identical. CONCLUSION: It may been recommended that 5 mg olanzapine plus tropisetron and dexamethasone, omitting aprepitant triplet regimen as an alternative therapy in prevention CINV induced by multiple-day cisplatin chemotherapy due to the excellent CINV control rate and safety.


Asunto(s)
Antieméticos , Antineoplásicos , Antieméticos/uso terapéutico , Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Aprepitant/uso terapéutico , Cisplatino/efectos adversos , Dexametasona/uso terapéutico , Humanos , Náusea/inducido químicamente , Náusea/tratamiento farmacológico , Náusea/prevención & control , Olanzapina/uso terapéutico , Estudios Prospectivos , Calidad de Vida , Tropisetrón/uso terapéutico , Vómitos/inducido químicamente , Vómitos/tratamiento farmacológico , Vómitos/prevención & control
2.
J Nanobiotechnology ; 20(1): 207, 2022 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-35501794

RESUMEN

As a typical class of crystalline porous materials, metal-organic framework possesses unique features including versatile functionality, structural and compositional tunability. After being reduced to two-dimension, ultrathin metal-organic framework layers possess more external excellent properties favoring various technological applications. In this review article, the unique structural properties of the ultrathin metal-organic framework nanosheets benefiting from the planar topography were highlighted, involving light transmittance, and electrical conductivity. Moreover, the design strategy and versatile fabrication methodology were summarized covering discussions on their applicability and accessibility, especially for porphyritic metal-organic framework nanosheet. The current achievements in the bioapplications of two-dimensional metal-organic frameworks were presented comprising biocatalysis, biosensor, and theranostic, with an emphasis on reactive oxygen species-based nanomedicine for oncology treatment. Furthermore, current challenges confronting the utilization of two-dimensional metal-organic frameworks and future opportunities in emerging research frontiers were presented.


Asunto(s)
Estructuras Metalorgánicas , Biocatálisis , Conductividad Eléctrica , Nanomedicina , Porosidad
3.
Int J Clin Pract ; 2022: 5954379, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36128262

RESUMEN

Objective: The significance of this article is to talk about aprepitant and olanzapine 5 mg, compare them, and deeply explore the safety or effectiveness during the whole process of multiple-day cisplatin chemotherapy-induced vomiting and nausea. Methods: This trial was randomized and prospective. It is needed to receive cisplatin chemotherapy (25 mg/m2/d) for three days. Its patients would need to choose to use 5 mg olanzapine or aprepitant for this treatment, combined with 5-HT3 receptor antagonist plus dexamethasone. The primary endpoints were the total protection (TP) during the acute phase (AP) (0-24 hours), delayed phase (DP) (25-120 hours), and overall phase (OP) (0-120 h) between the two groups. The secondary endpoints were the complete response (CR) and total control (TC) during the three phases. The first time of the whole process is particularly important and needs to be observed vigorously. However, the time of the patient's first vomiting symptom is also compared accurately by using the Kaplan-Meier curve. The functional life index vomiting (FLIE) was used to calculate and carefully evaluate the serious impact of nausea and vomiting (CINV) induced by the whole chemotherapy process on the quality of life. About olanzapine, its related symptoms and other side effects and aprepitant were also recorded. Results: (1) The primary endpoint TP rates of the olanzapine and aprepitant groups were similar; for the AP, they were 94.23% (98/104) vs. 95.45% (98/106) P=0.61(P=0.61); for the DP, they were 54.81% (57/104) vs. 54.72% (58/106) (P=0.99), and for the OP, the values were 53.79% (58/105) and 55.31% (56/104), respectively (P=0.99). The secondary endpoints, the TC rates, and CR rates were also comparable in the three phases (P > 0.05). (2) After research and display, the results showed that there was no significant difference between the two groups when they were used for the first time of vomiting and the FLIE index (P > 0.05). (3) The main olanzapine-related adverse event was drowsiness, while that of aprepitant was constipation. Conclusion: The efficacy of 5 mg olanzapine was similar to that of aprepitant, and it also showed an advantageous economic potency ratio in preventing CINV induced by multiple-day cisplatin chemotherapy with increased sedation side effects.


Asunto(s)
Antieméticos , Antineoplásicos , Aprepitant , Olanzapina , Antieméticos/uso terapéutico , Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Aprepitant/uso terapéutico , Cisplatino/efectos adversos , Dexametasona/uso terapéutico , Humanos , Náusea/inducido químicamente , Náusea/tratamiento farmacológico , Náusea/prevención & control , Olanzapina/uso terapéutico , Estudios Prospectivos , Calidad de Vida , Receptores de Serotonina 5-HT3/uso terapéutico , Vómitos/inducido químicamente , Vómitos/tratamiento farmacológico , Vómitos/prevención & control
4.
AAPS PharmSciTech ; 21(5): 192, 2020 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-32661608

RESUMEN

This study aimed to develop a self-nanoemulsifying drug delivery system (SNEDDS) for poorly water-soluble drug stiripentol (STP) with enhanced oral bioavailability. Optimal excipients were selected by constructing pseudo-ternary phase diagrams using determined solubilities of STP, and then the proper composition of SNEDDS was investigated by employing a central composite design method. The optimized SNEDDS was composed of oil (ethyl oleate 39.61%), surfactant (Cremophor® RH 40 43.18%), co-surfactant (1,2-propanediol 17.21%), and STP of 50 mg/mL. The hydrodynamic size, zeta potential, and polydispersity index (PDI) were found to be 45.52 ± 1.99 nm, - 21.67 ± 0.24 mV, and 0.076 ± 0.011, respectively. The optimized STP-SNEDDS showed good stability in accelerated and dilution stability studies. It was also helpful to suppress STP degradation in acidic solution. Compared with STP suspension, STP-SNEDDS presented much faster dissolution rate. STP-SNEDDS successfully resulted in superior levels of Cmax and AUC0 → 6 h (4048.38 ± 704.54 µg/L and 7754.58 ± 1489.37 h µg/L, respectively) to STP suspension (1894.09 ± 1077.64 µg/L and 3556.93 ± 2470.01 h µg/L, respectively). The relative oral bioavailability of STP was 218.01%. The brain biodistribution studies showed that STP-SNEDDS presented significantly higher STP concentrations in the brain at 0.5 h and 1 h than that of STP suspension after administration. These findings indicated that a SNEDDS-based oral formulation of STP would be helpful for increasing its therapeutic potential.


Asunto(s)
Anticonvulsivantes/farmacocinética , Dioxolanos/farmacocinética , Administración Oral , Anticonvulsivantes/administración & dosificación , Disponibilidad Biológica , Niño , Dioxolanos/administración & dosificación , Sistemas de Liberación de Medicamentos/métodos , Emulsiones , Excipientes , Humanos , Nanopartículas/administración & dosificación , Tamaño de la Partícula , Polietilenglicoles , Solubilidad , Distribución Tisular
5.
Molecules ; 19(12): 19594-609, 2014 Nov 26.
Artículo en Inglés | MEDLINE | ID: mdl-25432011

RESUMEN

Osteoporosis is a common skeletal disease caused by decreased bone mass; it enhances the risk of bone fracture. This study aimed to discover novel herbal extract(s) for the treatment of osteoporosis. We screened 64 ethanol extracts of edible plants native to Korea for their ability to increase the cellular proliferation and differentiation of two osteoblastic cell lines: C3H10T1/2 and MC3T3-E1. We selected a Lycii Radicis Cortex (LRC), Lycium Chinese root bark as the primary candidate. Treatment with LRC extract showed enhanced alkaline phosphatase activity and increased expression of bone metabolic markers Alpl, Runx2, and Bglap genes in both osteoblastic cell lines. There was no effect on the osteoclastic differentiation of primary-cultured monocytes from the mouse bone marrows. Furthermore, the study examined the effect of LRC extract in vivo in ovariectomizd (OVX) mice for 8 weeks and 16 weeks, respectively. Bone mineral density (BMD) was significantly higher in LRC extract-administered group than in the non-LRC-administered OVX control group. The results indicated that LRC extract prevented the OVX-induced BMD loss in mice via promoting the differentiation of osteoblast linage cells. These results suggest that LRC extract may be a good natural herbal medicine candidate for the treatment of osteoporosis.


Asunto(s)
Medicamentos Herbarios Chinos/farmacología , Osteogénesis/efectos de los fármacos , Extractos Vegetales/farmacología , Animales , Biomarcadores/metabolismo , Densidad Ósea/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Línea Celular , Proliferación Celular/efectos de los fármacos , Cromatografía Líquida de Alta Presión , Medicamentos Herbarios Chinos/química , Femenino , Lycium/química , Ratones , Osteoblastos/citología , Osteoblastos/efectos de los fármacos , Osteoblastos/metabolismo , Ovariectomía , Extractos Vegetales/química , ARN Mensajero/genética , ARN Mensajero/metabolismo , República de Corea , Espectrometría de Masa por Ionización de Electrospray
6.
Medicine (Baltimore) ; 102(21): e33877, 2023 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-37233418

RESUMEN

BACKGROUND: Ginkgo biloba L. leaves (GBLs) play a substantial role in the treatment of vascular dementia (VD); however, the underlying mechanisms of action are unclear. OBJECTIVE: This study was conducted to investigate the mechanisms of action of GBLs in the treatment of VD through network pharmacology, molecular docking, and molecular dynamics simulations. METHODS: The active ingredients and related targets of GBLs were screened using the traditional Chinese medicine systems pharmacology, Swiss Target Prediction and GeneCards databases, and the VD-related targets were screened using the OMIM, DrugBank, GeneCards, and DisGeNET databases, and the potential targets were identified using a Venn diagram. We used Cytoscape 3.8.0 software and the STRING platform to construct traditional Chinese medicine-active ingredient-potential target and protein-protein interaction networks, respectively. After gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis of potential targets using the DAVID platform, the binding affinity between key active ingredients and targets was analyzed by molecular docking, and finally, the top 3 proteins-ligand pairs with the best binding were simulated by molecular dynamics to verify the molecular docking results. RESULTS: A total of 27 active ingredients of GBLs were screened and 274 potential targets involved in the treatment of VD were identified. Quercetin, luteolin, kaempferol, and ginkgolide B were the core ingredients for treatment, and AKT1, TNF, IL6, VEGFA, IL1B, TP53, CASP3, SRC, EGFR, JUN, and EGFR were the main targets of action. The main biological processes involved apoptosis, inflammatory response, cell migration, lipopolysaccharide response, hypoxia response, and aging. PI3K/Akt appeared to be a key signaling pathway for GBLs in the treatment of VD. Molecular docking displayed strong binding affinity between the active ingredients and the targets. Molecular dynamics simulation results further verified the stability of their interactions. CONCLUSION SUBSECTIONS: This study revealed the potential molecular mechanisms involved in the treatment of VD by GBLs using multi-ingredient, multi-target, and multi-pathway interactions, providing a theoretical basis for the clinical treatment and lead drug development of VD.


Asunto(s)
Demencia Vascular , Medicamentos Herbarios Chinos , Humanos , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Ginkgo biloba , Farmacología en Red , Fosfatidilinositol 3-Quinasas , Hojas de la Planta , Receptores ErbB , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Medicina Tradicional China
7.
BMC Med Genomics ; 16(1): 276, 2023 11 03.
Artículo en Inglés | MEDLINE | ID: mdl-37924126

RESUMEN

PURPOSE: We aim to investigate the correlation between gene polymorphisms and cisplatin chemotherapy-induced nausea and vomiting (CINV), which was prevented by olanzapine or aprepitant triple antiemetic regimen. METHODS: Before chemotherapy, the blood samples of 89 malignant tumor patients who received multi-day chemotherapy with cisplatin were collected for sequencing and typing. As there were duplicate patients enrolled in different chemotherapy cycles, there were a total of 190 cases. The patients were divided into two groups randomly, who received the triple antiemetic regimen of olanzapine or aprepitant combined with 5-HT3RA and dexamethasone. The main evaluation indicators were the total protection (TP) rate in the acute phase (0-24 h), the delayed phase (25-120 h) and the overall phase (0-120 h). RESULTS: Univariate analysis was performed on genetic loci that reached H-W balance with TP. In the olanzapine group, increased TP in the acute phase was associated with HTR3A rs1176719 non-GG (P < 0.05) genotype etc. Increased TP in the delayed phase was associated with HTR3A rs1176719 non-GG (P < 0.05) genotype etc. In the aprepitant group, increased TP in the acute phase was associated with the MTHFR rs1801131 TT (P < 0.05) genotype etc. Increased TP in the delayed phase was associated with HTR3A rs1062613 CC (P < 0.05) genetype ect. Multivariate Logistic regression analysis showed that HTR3B rs7943062GG (P < 0.05) genotype etc. were correlated with increased TP in the delayed phase. MTHFR rs1801131TT genotype was associated with increased TP in the acute phase (P < 0.05) and delayed phase (P < 0.05). CONCLUSION: This study found that gene polymorphisms, including HTR3B (rs1062613, rs1176719, rs2276303), HTR3B (rs45460698, rs7943062), HTR3C (rs6766410), ERCC1 (rs3212986), ERCC4 (rs744154) and MTHFR(rs1801131), may be independent prognostic factors for CINV.


Asunto(s)
Antineoplásicos , Cisplatino , Humanos , Antieméticos/uso terapéutico , Antineoplásicos/efectos adversos , Aprepitant/uso terapéutico , Cisplatino/efectos adversos , Náusea/inducido químicamente , Náusea/genética , Náusea/tratamiento farmacológico , Olanzapina/uso terapéutico , Polimorfismo Genético , Vómitos/inducido químicamente , Vómitos/genética , Vómitos/tratamiento farmacológico
8.
Adv Healthc Mater ; 12(23): e2300524, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37269141

RESUMEN

Vaccination immunotherapy has revolutionized cancer treatment modalities. Although the immunomodulatory adjuvant generally employs for potentiating vaccine response, systemic administration may drive immune-related side effects, even immune tolerance. Therefore, tunable immunoadjuvants are highly desirable to simultaneously stimulate the immune response and mitigate systemic toxicity. Self-immolated nanoadjuvants are herein reported to potentiate vaccination immunotherapy of cancer. The nanoadjuvants are engineered by co-assembling an intracellular acidity-ionizable polymeric agonist of toll-like receptor 7/8 resiquimod (R848) and polymeric photosensitizer pyropheophorbide a (PPa). The resultant nanoadjuvants specifically accumulate at the tumor site via passive targeting and are dissociated in the acidic endosome versicles to activate PPa via protonation of the polymer backbone. Upon 671 nm laser irradiation, PPa performed photodynamic therapy to induce immunogenic cell death of tumor cells and subsequently releases R848 in a customized manner, which synergistically activates dendritic cells (DCs), promotes antigen cross-presentation, and eventually recruits cytotoxic T lymphocytes for tumor regression. Furthermore, the synergistic in situ vaccination immunotherapy with immune checkpoint blockade induce sustained immunological memory to suppress tumor recurrence in the rechallenged colorectal tumor model.


Asunto(s)
Neoplasias Colorrectales , Células Dendríticas , Humanos , Células Dendríticas/metabolismo , Inmunoterapia , Linfocitos T Citotóxicos , Neoplasias Colorrectales/terapia , Neoplasias Colorrectales/metabolismo , Adyuvantes Inmunológicos , Vacunación
9.
Genes (Basel) ; 13(3)2022 03 03.
Artículo en Inglés | MEDLINE | ID: mdl-35328013

RESUMEN

The systemic gene interactions that occur during osteoporosis and their underlying mechanisms remain to be determined. To this end, mesenchymal stromal cells (MSCs) were analyzed from bone marrow samples collected from healthy individuals (n = 5) and patients with osteoporosis (n = 5). A total of 120 osteoporosis-related genes were identified using RNA-sequencing (RNA-seq) and Ingenuity Pathway Analysis (IPA) software. In order to analyze these genes, we constructed a heatmap of one-way hierarchical clustering and grouped the gene expression patterns of the samples. The MSCs from one control participant showed a similar expression pattern to that observed in the MSCs of three patients with osteoporosis, suggesting that the differentiating genes might be important genetic determinants of osteoporosis. Then, we selected the top 38 genes based on fold change and expression, excluding osteoporosis-related genes from the control participant. We identified a network among the top 38 genes related to osteoblast and osteoclast differentiation, bone remodeling, osteoporosis, and sarcopenia using the Molecule Activity Predictor program. Among them, 25 genes were essential systemic genes involved in osteoporosis. Furthermore, we identified 24 genes also associated with diabetes and obesity, among which 10 genes were involved in a network related to bone and energy metabolism. The study findings may have implications for the treatment and prevention of osteoporosis.


Asunto(s)
Diabetes Mellitus , Células Madre Mesenquimatosas , Osteoporosis , Sarcopenia , Células de la Médula Ósea/metabolismo , Diabetes Mellitus/metabolismo , Redes Reguladoras de Genes , Humanos , Obesidad/genética , Obesidad/metabolismo , Osteogénesis/genética , Osteoporosis/genética , Sarcopenia/genética , Sarcopenia/metabolismo
10.
Bioact Mater ; 6(12): 4301-4318, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33997507

RESUMEN

In recent years, reactive species-based cancer therapies have attracted tremendous attention due to their simplicity, controllability, and effectiveness. Herein, we overviewed the state-of-art advance for photo-controlled generation of highly reactive radical species with nanomaterials for cancer therapy. First, we summarized the most widely explored reactive species, such as singlet oxygen, superoxide radical anion (O2 ●-), nitric oxide (●NO), carbon monoxide, alkyl radicals, and their corresponding secondary reactive species generated by interaction with other biological molecules. Then, we discussed the generating mechanisms of these highly reactive species stimulated by light irradiation, followed by their anticancer effect, and the synergetic principles with other therapeutic modalities. This review might unveil the advantages of reactive species-based therapeutic methodology and encourage the pre-clinical exploration of reactive species-mediated cancer treatments.

11.
Int J Gen Med ; 14: 5879-5892, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34566427

RESUMEN

The occurrence and severity of chemotherapy-induced nausea and vomiting (CINV) are influenced by many factors; this includes therapeutic factors, such as the dose, administration mode, and chemotherapeutic agent emetogenicity, as well as patient-related risk factors, such as the gender, age, alcohol consumption history, and anxiety level. However, these factors cannot fully explain the individual CINV differences. In recent years, the correlation between gene polymorphism and CINV has been a hot research topic; the present paper reviews current research on CINV-related gene polymorphisms, and the results indicate that the use of gene polymorphism for the optimization of CINV efficacy is of important clinical significance.

12.
Pharmgenomics Pers Med ; 14: 867-875, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34290520

RESUMEN

OBJECTIVE: The present study aims to investigate the correlation between the gene polymorphisms of the multidrug resistance protein 1 (ABCB1), the intron region of transcriptional factor (GTF2E1) and catechol-O-methyltransferase (COMT), dopamine receptor (DRD2), and the control of chemotherapy-induced nausea and vomiting (CINV) by olanzapine or aprepitant in a Chinese population under a fractionated cisplatin dosing pattern. METHODS: Antiemetic treatment with 5 mg of olanzapine or aprepitant triplet therapy was conducted in 210 patients with malignancies receiving cisplatin multi-day chemotherapy. The general data on the patients were collected with the evaluation of the rate of complete protection (TP), complete remission (CR), complete control (TC), and time to first vomiting, the functional living index-emesis (FLIE) scale, and side effects in the acute and delayed phases. The DNA mass spectrometry detected the gene polymorphisms of ABCB1, GTF2E1, COMT, and DRD2, and the correlation with TP was analyzed. RESULTS: 1) There were no statistically significant differences in the TP, CR, TC, time of first vomiting, and FLIE index at different phases between the 5mg of olanzapine group and the aprepitant group (P > 0.05). 2) The main side effect in the olanzapine group was drowsiness (P = 0.00), and in the aprepitant group was constipation (P = 0.02). 3) The distributions of each genotype were in the Hardy-Weinberg (H-W) equilibrium. Univariate analysis showed that in the olanzapine group, delayed-phase TP was correlated with the ABCB1 rs1045642 non-TT (P = 0.01) genotype. CONCLUSION: The present study revealed that females and the rs1045642TT genotype were independent risk factors for delayed-phase CINV in the northern Chinese population, which provided a scientific basis for subsequent CINV-related analysis of high-risk factors in Chinese patients.

13.
ACS Biomater Sci Eng ; 6(9): 4834-4845, 2020 09 14.
Artículo en Inglés | MEDLINE | ID: mdl-33455215

RESUMEN

Chemodynamic therapy (CDT) has aroused extensive attention for cancer treatment in the last five years, as it could suppress tumor progression through in situ detrimental oxidative stress of the tumor cells via the Fenton reaction. Under a tumor acidic microenvironment, the Fenton reaction can be initiated for disproportioning endogenous hydrogen peroxide into highly toxic hydroxyl radical. Taking advantage of the highly tumor-specific therapy modality, various Fenton nanocatalysts have been developed for CDT. In particular, iron-containing Fenton nanocatalysts with minimal cytotoxicity exhibit great promise for clinical translation. In this review, we summarize the recent progress of CDT based on iron-containing nanomaterials, including iron oxide nanoparticles, glassy iron nanoclusters, ferrocene nanoparticles, metal polyphenol networks, metal-organic frameworks, etc. We also discuss the challenges and perspectives for promoting CDT by rational design of iron-containing nanomaterials, highlighting their potential for precise cancer therapy.


Asunto(s)
Nanopartículas , Neoplasias , Humanos , Hierro , Neoplasias/tratamiento farmacológico , Medicina de Precisión , Microambiente Tumoral
14.
Artículo en Inglés | MEDLINE | ID: mdl-32011108

RESUMEN

Chemodynamic therapy (CDT) takes the advantages of Fenton-type reactions triggered by endogenous chemical energy to generate highly cytotoxic hydroxyl radicals. As a novel modality for cancer treatment, CDT shows minimal invasiveness and high tumor specificity by responding to the acidic and the highly concentrated hydrogen peroxide microenvironment of tumor. The CDT approach for spatiotemporal controllable reactive oxygen species generation exhibits preferable therapeutic performance and satisfying biosafety. In this review article, we summarized the recent advances of stimuli-activatable nanomedicines for CDT. We also overviewed the strategies for augmenting CDT performance, including increasing the catalytic efficacy through rational design of the nanomaterials, modulating the reaction condition, inputting external energy field, and regulating the tumor microenvironment. Furthermore, we discussed the potential and challenges of stimuli-activatable nanomedicine for clinical translation and future development of CDT. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Diagnostic Tools > In Vivo Nanodiagnostics and Imaging.


Asunto(s)
Nanomedicina , Neoplasias/tratamiento farmacológico , Animales , Glutatión/química , Humanos , Radical Hidroxilo/química , Nanopartículas/química , Microambiente Tumoral
15.
Sci Rep ; 10(1): 2385, 2020 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-32024936

RESUMEN

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

16.
Sci Rep ; 9(1): 6773, 2019 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-31043660

RESUMEN

Calcification is important for the diagnosis of papillary thyroid carcinoma (PTC). Runt-related transcription factor 2 (RUNX2), a master transcription factor associated with osteogenic differentiation, is reportedly related to PTC calcification and invasiveness. However, its regulatory role in this process is somewhat uncharacterized. Here, we attempted to identify genes that regulate RUNX2 and clarify its function in PTC carcinogenesis and calcification. The expression of RUNX2-upstream genes was evaluated by real-time PCR in Nthy-Ori 3-1 normal thyroid cells and TPC1 and BHP10-3 PTC cell lines. Luciferase and chromatin immunoprecipitation assays were performed with candidate genes after cloning the RUNX2 promoter. We found that RUNX2 promoter activity was enhanced by homeobox family A9 (HOXA9). Over-expression of HOXA9 was found to enhance alkaline phosphatase activity, mineralization, and in vitro tumour cell migration and invasion, whereas downregulation had the opposite effects. These results indicate that HOXA9, a positive regulator of RUNX2, can enhance calcification, migration, and invasion in PTC. Our data improve the understanding of the molecular mechanisms of microcalcification in PTC as well as tumorigenesis.


Asunto(s)
Calcinosis/patología , Proteínas de Homeodominio/metabolismo , Cáncer Papilar Tiroideo/patología , Neoplasias de la Tiroides/patología , Apoptosis , Calcinosis/genética , Calcinosis/metabolismo , Proliferación Celular , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Proteínas de Homeodominio/genética , Humanos , Invasividad Neoplásica , Cáncer Papilar Tiroideo/genética , Cáncer Papilar Tiroideo/metabolismo , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/metabolismo , Células Tumorales Cultivadas
17.
Mol Med Rep ; 16(4): 4075-4081, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-29067460

RESUMEN

To identify novel candidate genes associated with osteoporosis, RNA­sequence analysis of human mesenchymal stem cells (hMSCs) from patients with osteoporosis (G3) and osteopenia (G2), and healthy controls (G1) was performed. Differentially expressed genes (DEGs) from among the three groups were identified. DEGs were separated into nine groups according to their gene expression patterns: UU (up and up), UF (up and flat), UD (up and down), FU (flat and up), FF (flat and flat), FD (flat and down), DU (down and up), DF (down and flat), and DD (down and down). Among the 42 DEGs between G3 and G1, eight candidate genes, namely stimulated by retinoic acid 6 (STRA6), melanophilin, neurotrophic receptor tyrosine kinase 2, cartilage oligomeric matrix protein, collagen type XI α 1 chain, integrin subunit ß 2, monooxygenase DBH­like 1 and selenoprotein P, were selected, as they demonstrated consistent gene expression patterns of UU, FU, FD, and DD. Among these eight genes, STRA6 was highly expressed in the osteoporosis group and based on additional data from quantitative polymerase chain reaction analysis, it was selected for further study. In order to investigate whether STRA6 served a functional role in osteoblast or adipocyte differentiation, the effects of STRA6 expression changes in pluripotent stem cell C3H10T1/2, preosteoblast MC3T3­E1 and stromal ST2 cell lines were examined. Bone morphogenetic protein 2 enhanced STRA6 expression only at the early stage of osteoblast differe-ntiation, and overexpression of STRA6 temporally inhibited the expression of osteoblastogenesis markers, including runt related transcription factor 2, bone sialoprotein and osteocalcin. Furthermore, the knockdown of STRA6 slightly enhanced nodule formation at the late stage of osteoblast differentiation, and overexpression of STRA6 in ST2 cells enhanced adipocyte differentiation. Taken together, STRA6 expression could be associated with the pathogenesis of osteoporosis by promoting adipocyte differentiation over osteoblast differentiation in the hMSC population.


Asunto(s)
Proteínas de la Membrana/metabolismo , Osteoporosis/patología , ARN/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Anciano , Animales , Enfermedades Óseas Metabólicas/metabolismo , Enfermedades Óseas Metabólicas/patología , Células de la Médula Ósea/citología , Diferenciación Celular , Células Cultivadas , Femenino , Regulación de la Expresión Génica , Humanos , Masculino , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Proteínas de la Membrana/antagonistas & inhibidores , Proteínas de la Membrana/genética , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Ratones , Persona de Mediana Edad , Osteoblastos/citología , Osteoblastos/metabolismo , Osteocalcina/genética , Osteocalcina/metabolismo , Osteogénesis , Osteoporosis/metabolismo , ARN/química , ARN/aislamiento & purificación , Interferencia de ARN , Receptor trkB/genética , Receptor trkB/metabolismo
18.
Gene ; 632: 7-15, 2017 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-28844671

RESUMEN

Genetic alterations are major contributing factors in the development of osteoporosis. Osteoblasts and adipocytes share a common origin, mesenchymal stem cells (MSCs), and their genetic determinants might be important in the relationship between osteoporosis and obesity. In the present study, we aimed to isolate differentially expressed genes (DEGs) in osteoporosis and normal controls using human MSCs, and elucidate the common pathways and genes related to osteoporosis and adipogenesis. Human MSCs were obtained from the bone marrow of femurs from postmenopausal women during orthopedic surgeries. RNA sequencing (RNA-seq) was carried out using next-generation sequencing (NGS) technology. DEGs were identified using RNA-seq data. Ingenuity pathway analysis (IPA) was used to elucidate the common pathway related to osteoporosis and adipogenesis. Candidate genes for the common pathway were validated with other independent osteoporosis and obese subjects using RT-PCR (reverse transcription-polymerase chain reaction) analysis. Fifty-three DEGs were identified between postmenopausal osteoporosis patients and normal bone mineral density (BMD) controls. Most of the genetic changes were related to the differentiation of cells. The nuclear receptor subfamily 4 group A (NR4A) family was identified as possible common genes related to osteogenesis and adipogenesis. The expression level of the mRNA of NR4A1 was significantly higher in osteoporosis patients than in controls (p=0.018). The expression level of the mRNA of NR4A2 was significantly higher in obese patients than in controls (p=0.041). Some genetic changes in MSCs are involved in the pathophysiology of osteoporosis. The NR4A family might comprise common genes related to osteoporosis and obesity.


Asunto(s)
Adipogénesis , Células Madre Mesenquimatosas/metabolismo , Osteoporosis Posmenopáusica/genética , Transcriptoma , Anciano , Animales , Estudios de Casos y Controles , Células Cultivadas , Femenino , Fémur/citología , Humanos , Células Madre Mesenquimatosas/citología , Ratones , Persona de Mediana Edad , Receptores Nucleares Huérfanos/genética , Receptores Nucleares Huérfanos/metabolismo , Osteoblastos/citología , Osteoblastos/metabolismo , Osteogénesis , Osteoporosis Posmenopáusica/metabolismo
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