RESUMEN
Purpose: The present study aimed to develop a lipid nanoplatform, denoted as "BAL-PTX-LN", co-loaded with chiral baicalin derivatives (BAL) and paclitaxel (PTX) to promote the anti-lung cancer efficacy of paclitaxel and reduce the toxicity of chemotherapeutic drugs. Methods: BAL-PTX-LN was optimized through central composite design based on a single-factor experiments. BAL-PTX-LN was evaluated by TEM, particle size, encapsulation efficiency, hemolysis rate, release kinetics and stability. And was evaluated by pharmacokinetics and the antitumor efficacy studied both in vitro and in vivo. The in vivo safety profile of the formulation was assessed using hematoxylin and eosin (HE) staining. Results: BAL-PTX-LN exhibited spherical morphology with a particle size of 134.36 ± 3.18 nm, PDI of 0.24 ± 0.02, and with an encapsulation efficiency exceeding 90%, BAL-PTX-LN remained stable after 180 days storage. In vitro release studies revealed a zero-order kinetic model of PTX from the liposomal formulation. No hemolysis was observed in the preparation group. Pharmacokinetic analysis of PTX in the BAL-PTX-LN group revealed an approximately three-fold higher bioavailability and twice longer t1/2 compared to the bulk drug group. Furthermore, the IC50 of BAL-PTX-LN decreased by 2.35 times (13.48 µg/mL vs 31.722 µg/mL) and the apoptosis rate increased by 1.82 times (29.38% vs 16.13%) at 24 h compared to the PTX group. In tumor-bearing nude mice, the BAL-PTX-LN formulation exhibited a two-fold higher tumor inhibition rate compared to the PTX group (62.83% vs 29.95%), accompanied by a ten-fold decrease in Ki67 expression (4.26% vs 45.88%). Interestingly, HE staining revealed no pathological changes in tissues from the BAL-PTX-LN group, whereas tissues from the PTX group exhibited pathological changes and tumor cell infiltration. Conclusion: BAL-PTX-LN improves the therapeutic effect of poorly soluble chemotherapeutic drugs on lung cancer, which is anticipated to emerge as a viable therapeutic agent for lung cancer in clinical applications.
Asunto(s)
Neoplasias Pulmonares , Paclitaxel , Paclitaxel/química , Paclitaxel/farmacocinética , Paclitaxel/farmacología , Paclitaxel/administración & dosificación , Animales , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Humanos , Flavonoides/química , Flavonoides/farmacología , Flavonoides/farmacocinética , Flavonoides/administración & dosificación , Tamaño de la Partícula , Nanopartículas/química , Ratones , Liposomas/química , Liposomas/farmacocinética , Células A549 , Lípidos/química , Masculino , Ratones Endogámicos BALB C , Línea Celular Tumoral , Liberación de Fármacos , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacocinética , Ratones Desnudos , Hemólisis/efectos de los fármacos , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/farmacocinética , Antineoplásicos/administración & dosificaciónRESUMEN
Herein, a microwave promoted tandem reaction of free primary arylamines with diazo compounds in water for clean synthesis of 2,2-disubstituted 3-oxindoles is present. Water plays important roles in the whole cascade process: O-H insertion to diazo, air oxidation, ortho C-H functionalization, cyclization and 1,2-ester migration. In particular, water plays a mediation role in the site selective ortho-C-H addition.
RESUMEN
The aim of this study was to develop a novel antidepressant with high activity. Based on the findings of molecular docking, eight novel curcumin analogues were evaluated in vitro to check for antidepressant efficacy. Among them, CACN136 had the strongest antidepressant effect. Firstly, CACN136 had a stronger 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonate) radical ion scavenging ability (IC50: 17.500 ± 0.267 µg/mL) compared to ascorbic acid (IC50: 38.858 ± 0.263 µg/mL) and curcumin (27.189 ± 0.192 µg/mL). Secondly, only CACN136 demonstrated clear protective effects on cells damaged by glutamate and oxidative stress at all concentrations. Finally, only CACN136 showed ASP + inhibition and was more effective than fluoxetine hydrochloride (FLU) at low concentrations. To further confirm the antidepressant effect of CACN136 in vivo, the CUMS model was established. Following 28 days of oral administration of CUMS mice, CACN136 increased the central area residence time in the open-field test, significantly increased the sucrose preference rate in the sucrose preference test (P < 0.001) and significantly reduced the immobility period in the tail suspension test (P < 0.0001), all of which were more effective than those of FLU. Subsequent research indicated that the antidepressant properties of CACN136 were linked to a decrease in the metabolism of 5-HT and the modulation of oxidative stress levels in vivo. In particular, the activation of the Keap1-Nrf2/BDNF-TrkB signaling pathway by CACN136 resulted in elevated levels of antioxidant enzymes, enhancing the antioxidant capability in mice subjected to CUMS. In conclusion, CACN136 has the potential to treat depression and could be an effective antidepressant.
RESUMEN
The de novo construction of enantioenriched 3-hydroxyindolenines and 3-oxindoles from easily available starting materials has been highly desired. Herein, an enantioselectively intermolecular direct [3 + 2] annulation of aryl amine with 2,3-diketoesters to construct 3-hydroxyindolenines with a chiral tertiary alcohol has been disclosed. The results of control experiments and DFT calculation revealed that π - π interaction plays a pivotal role in the enantioselectivity-determining process of [3 + 2] annulation. The following unusual concerted [1,2]-ester migration provides a family of chiral 3-oxindoles in good to excellent yields with excellent enantioselectivity.
RESUMEN
C-3 amidated imidazoheterocycles were synthesized via a visible light-promoted reaction of imidazoheterocycles with N-amidopyridinium salts catalyzed by 4CzIPN under mild conditions. For imidazoheterocycles and N-amidopyridinium salts with various substituents, the reaction proceeded smoothly to give the corresponding products in moderate to good yields. The reaction provides a new strategy for the synthesis of secondary amides with the imidazo[1,2-a]pyridine core.
RESUMEN
There has been an increase in cardiovascular morbidity and mortality over the past few decades, making cardiovascular disease (CVD) the leading cause of death worldwide. However, the pathogenesis of CVD is multi-factorial, complex, and not fully understood. The gut microbiome has long been recognized to play a critical role in maintaining the physiological and metabolic health of the host. Recent scientific advances have provided evidence that alterations in the gut microbiome and its metabolites have a profound influence on the development and progression of CVD. Among the trillions of microorganisms in the gut, bifidobacteria, which, interestingly, were found through the literature to play a key role not only in regulating gut microbiota function and metabolism, but also in reducing classical risk factors for CVD (e.g., obesity, hyperlipidemia, diabetes) by suppressing oxidative stress, improving immunomodulation, and correcting lipid, glucose, and cholesterol metabolism. This review explores the direct and indirect effects of bifidobacteria on the development of CVD and highlights its potential therapeutic value in hypertension, atherosclerosis, myocardial infarction, and heart failure. By describing the key role of Bifidobacterium in the link between gut microbiology and CVD, we aim to provide a theoretical basis for improving the subsequent clinical applications of Bifidobacterium and for the development of Bifidobacterium nutritional products.
Asunto(s)
Enfermedades Cardiovasculares , Enfermedades Metabólicas , Humanos , Enfermedades Cardiovasculares/terapia , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/metabolismo , Bifidobacterium , Factores de Riesgo , Obesidad , Enfermedades Metabólicas/complicacionesRESUMEN
Pd(II) catalysts, particularly the acetate salt in acetic acid, tended to favor regioselective C-H activation of quinoline N-oxides (QOs) at the C2 position. However, Pd(II)Cl2 was shown to catalyze their C-H activation at C8 and, in the presence of water, C8-H activation was accompanied by the formation of 2-quinolinones. The aim of the DFT study described in this work was to shed light on the complete mechanism of these competing catalytic reactions, when PdCl2 reacts with QO and benzaldehyde in dichloroethane. C-H activation of QO was the first step of the reaction and involved either a metallacycle, with a CQO-Pd(II) σ-bond and a C(8)-H-Pd(II) agostic bond, or an η3-QO complex, with three carbon atoms of the heteroring of QO binding PdCl2. The first situation led to the unusual C8 activation and the second to C2 activation. The σ-metallacycle undergoes C8-H activation and the energy of the TOF determining the transition state to form the product is â¼17 kcal mol-1, while for the reaction through the π-metallacycle (C2-H activation) the corresponding energy is higher (â¼29 kcal mol-1) and thus is not competitive under the same conditions. The reaction proceeding through the σ-complex, activating the C8 position, is preferred, in agreement with experimental results. Both reactions involve oxidation of Pd(II) to Pd(IV) and the catalyst is regenerated. When small amounts of water are added to the reaction mixture, C8-H activation (acylation) results from the same σ-metallacycle with the same barrier, but the simultaneous formation of 2-quinolinones is more complicated. It starts with OH- attack at the C2 position, and is followed by the migration of two hydrogen atoms, and the final reductive elimination step ends with Pd(0). The higher barriers for the migration and reoxidation of Pd(0) are associated with the more demanding reaction conditions. The different reactivity of Pd(II)(OAc)2 under analogous conditions is clarified, as it is only capable of forming the above mentioned π-complex and thus of activating the C2 position of QO. This catalyst can preferentially activate the C8-H bond under rather different conditions, including in particular acetic acid medium, as shown by other authors.
RESUMEN
Major depressive disorder (MDD) is a chronic relapsing psychiatric disorder. Conventional antidepressants usually require several weeks of continuous administration to exert clinically significant therapeutic effects, while about two-thirds of the patients are prone to relapse of symptoms or are completely ineffective in antidepressant treatment. The recent success of the N-methyl-D-aspartic acid (NMDA) receptor antagonist ketamine as a rapid-acting antidepressant has propelled extensive research on the action mechanism of antidepressants, especially in relation to its role in synaptic targets. Studies have revealed that the mechanism of antidepressant action of ketamine is not limited to antagonism of postsynaptic NMDA receptors or GABA interneurons. Ketamine produces powerful and rapid antidepressant effects by affecting α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors, adenosine A1 receptors, and the L-type calcium channels, among others in the synapse. More interestingly, the 5-HT2A receptor agonist psilocybin has demonstrated potential for rapid antidepressant effects in depressed mouse models and clinical studies. This article focuses on a review of new pharmacological target studies of emerging rapid-acting antidepressant drugs such as ketamine and hallucinogens (e.g., psilocybin) and briefly discusses the possible strategies for new targets of antidepressants, with a view to shed light on the direction of future antidepressant research.
Asunto(s)
Trastorno Depresivo Mayor , Ketamina , Animales , Ratones , Ketamina/farmacología , Ketamina/uso terapéutico , Trastorno Depresivo Mayor/tratamiento farmacológico , Psilocibina/uso terapéutico , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Modelos Animales de Enfermedad , Receptores de N-Metil-D-AspartatoRESUMEN
Transition metal-controlled divergent annulation reactions of azomethine imines with iodonium ylides via C-centered [1,2]-rearrangement have been developed. The azomethine imino group, as a switchable and transient directing group (DG), underwent intramolecular nucleophilic addition and in situ generated bicyclic diaziridine, which facilitated the C-centered [1,2]-rearrangement and subsequent divergent annulations in the presence of different metal complexes as the catalysts. The benzo[c]chromen-1-one and pyrano[de]isochromene scaffolds could be independently constructed with Rh(III) and Ru(II), respectively. It was worth noting that the azomethine imino group was employed first as the switchable DG through rearrangement progress.
RESUMEN
Described herein is the development of an unprecedented approach to construct multiple heterocycles with high selectivity through Rh(III)-catalyzed two- or three-component cyclization reaction from simple and readily available starting materials: N-methoxybenzamides, 2-butyne biscarbonate, and maleimides. This methodology provides an efficient strategy for the synthesis of diverse and complicated heterocycles in a one-pot manner and displays excellent features of extremely mild reaction conditions, easy operation, excellent regioselectivity, and good functional group compatibility.
RESUMEN
Colorectal cancer (CRC) has high incidence and mortality rates and is one of the most common cancers of the digestive tract worldwide. Metastasis and drug resistance are the main causes of cancer treatment failure. Studies have recently suggested extracellular vesicles (EVs) as a novel mechanism for intercellular communication. They are vesicular particles, which are secreted and released into biological fluids, such as blood, urine, milk, etc., by a variety of cells and carry numerous biologically active molecules, including proteins, nucleic acids, lipids, metabolites, etc. EVs play a crucial part in the metastasis and drug resistance of CRC by delivering cargo to recipient cells and modulating their behavior. An in-depth exploration of EVs might facilitate a comprehensive understanding of the biological behavior of CRC metastasis and drug resistance, which might provide a basis for developing therapeutic strategies. Therefore, considering the specific biological properties of EVs, researchers have attempted to explore their potential as next-generation delivery systems. On the other hand, EVs have also been demonstrated as biomarkers for the prediction, diagnosis, and presumed prognosis of CRC. This review focuses on the role of EVs in regulating the metastasis and chemoresistance of CRC. Moreover, the clinical applications of EVs are also discussed.
Asunto(s)
Neoplasias Colorrectales , Vesículas Extracelulares , Humanos , Vesículas Extracelulares/metabolismo , Comunicación Celular , Biomarcadores/metabolismo , Resistencia a Medicamentos , Neoplasias Colorrectales/metabolismoRESUMEN
Depression is a common mental illness, which is related to monoamine neurotransmitters and the dysfunction of the cholinergic, immune, glutamatergic, and neuroendocrine systems. The hypothesis of monoamine neurotransmitters is one of the commonly recognized pathogenic mechanisms of depression; however, the drugs designed based on this hypothesis have not achieved good clinical results. A recent study demonstrated that depression and inflammation were strongly correlated, and the activation of alpha7 nicotinic acetylcholine receptor (α7 nAChR)-mediated cholinergic anti-inflammatory pathway (CAP) in the cholinergic system exhibited good therapeutic effects against depression. Therefore, anti-inflammation might be a potential direction for the treatment of depression. Moreover, it is also necessary to further reveal the key role of inflammation and α7 nAChR in the pathogenesis of depression. This review focused on the correlations between inflammation and depression as well-discussed the crucial role of α7 nAChR in the CAP.
Asunto(s)
Depresión , Receptor Nicotínico de Acetilcolina alfa 7 , Humanos , Receptor Nicotínico de Acetilcolina alfa 7/metabolismo , Colinérgicos , Inflamación/metabolismo , Neuroinmunomodulación , Depresión/metabolismoRESUMEN
TBAI-catalysed [4+4]-cyclization reaction of anthranils with hydrazones to deliver oxa-bridged eight-membered heterocycles in accepted yields was developed. Preliminary mechanistic studies indicated that the reaction involved the inâ situ generation of vinyldiazenes from readily available hydrazones followed by an aza-Michael addition of the anthranil substrates onto the vinyldiazenes and subsequent annulation. This transformation involved the formation of two new C-N bonds and C-O bond in one pot, overcoming the synthetic limitations of anthranils in organic chemistry. This strategy benefits from high efficiency and atomic economy with mild reaction conditions.
RESUMEN
Purpose: The early stage of this study verified that a turmeric extract (TUR) including 59% curcumin (CU), 22% demethoxycurcumin (DMC), and 18% bisdemethoxycurcumin (BDMC), could enhance the stability of CU and had greater antidepressant potential in vitro. The objective of the study was to develop a nano-delivery system containing TUR (TUR-NE) to improve the pharmacokinetic behavior of TUR and enhance its antidepressant effect. Methods: The antidepressant potential of TUR was explored using ABTS, oxidative stress-induced cell injury, and a high-throughput screening model. TUR-NE was fabricated, optimized and characterized. The pharmacokinetic behaviors of TUR-NE were evaluated following oral administration to normal rats. The antidepressant effect of TUR-NE was assessed within chronic unpredictable mild stress model (CUMS) mice. The behavioral and biochemical indexes of mice were conducted. Results: The results depicted that TUR had 3.18 and 1.62 times higher antioxidant capacity than ascorbic acid and CU, respectively. The inhibition effect of TUR on ASP+ transport was significantly enhanced compared with fluoxetine and CU. TUR-NE displayed a particle size of 116.0 ± 0.31 nm, polydispersity index value of 0.121 ± 0.007, an encapsulation rate of 98.45%, and good release and stability in cold storage. The results of pharmacokinetics indicated the AUC(0-t) of TUR-NE was 8.436 and 4.495 times higher than that of CU and TUR, while the Cmax was 9.012 and 5.452 times higher than that of CU and TUR, respectively. The pharmacodynamic study confirmed that the superior antidepressant effect of TUR-NE by significantly improving the depressant-like behaviors and elevating the content of 5-hydroxytryptamine in plasma and brain in CUMS mice. TUR-NE showed good safety with repeated administration. Conclusion: TUR-NE, which had small and uniform particle size, enhanced the bioavailability and antidepressant effect of TUR. It could be a promising novel oral preparation against depression.
Asunto(s)
Curcumina , Ratas , Ratones , Animales , Curcumina/farmacología , Antidepresivos/farmacología , Extractos Vegetales/química , Curcuma/químicaRESUMEN
Purpose: Paclitaxel (PTX) has been widely utilized for the treatment of breast cancer. However, drawbacks, such as poor aqueous solubility, rapid blood clearance and severe toxicity, greatly reduce its efficacy and safety. Herein, a novel self-developed curcumin derivative (CUD) was chosen as the carrier to develop a long-acting PTX nano-delivery system (PTX-Sln@CUD) in order to improve its pharmacokinetic behavior, anti-breast cancer efficacy and safety. Methods: PTX-Sln@CUD was prepared using solid dispersion and ultrasonic technology. Relevant physical and chemical properties, including stability and release behavior, were characterized. The clearance of PTX-Sln@CUD in vivo was studied by pharmacokinetic experiments. The anti-tumor activity of PTX-Sln@CUD was investigated in vitro and in vivo. Hemolysis experiments, acute toxicity and cumulative toxicity studies were performed in mice to determine the safety of PTX-Sln@CUD. Results: The average particle size, PDI, Zeta potential, encapsulation efficiency and loading efficiency of the PTX-Sln@CUD were 238.5 ± 4.79 nm, 0.225 ± 0.011, -33.8 ± 1.26 mV, 94.20 ± 0.49% and 10.98 ± 0.31%, respectively. PTX-Sln@CUD was found to be stable at room temperature for half a year. The cumulative release rates of PTX-Sln@CUD at 24, 96 and 168 h were 17.98 ± 2.60, 57.09 ± 2.32 and 72.66 ± 4.16%, respectively, which were adherent to zero-order kinetics. T1/2, MRT (0-t) and AUC (0-t) of the PTX-Sln@CUD group were 4.03-fold (44.293 h), 7.78-fold (38.444 h) and 6.18-fold (14.716 mg/L*h) of the PTX group, respectively. PTX-Sln@CUD group demonstrated stronger anti-breast cancer activity than the PTX group. Importantly, the PTX-Sln@CUD group was safer compared to the PTX group both in vitro and in vivo. Conclusion: PTX-Sln@CUD was verified as promising therapeutic nanoparticles for breast cancer and provided a novel strategy to solve the problem of low efficacy and poor safety of clinical chemotherapy drugs.
Asunto(s)
Curcumina , Nanopartículas , Ratones , Animales , Paclitaxel , Curcumina/farmacología , Nanopartículas/química , Tamaño de la PartículaRESUMEN
A highly regioselective synthesis of spiro[benzofuran-2,2'-furan]-3-ones has been explored via Lewis acid-catalyzed [3 + 2] cyclization of iodonium ylides with azadienes. The acidity of the Lewis acid was significantly strengthened with strong hydrogen bond donors, thereby promoting the enolization isomerization of iodonium ylides for the subsequent cycloaddition. This reaction was compatible with a broad range of substrates under the mild reaction conditions, and efficiently delivered spiro-heterocycles with excellent stereoselectivity.
RESUMEN
This study investigated the effect of structural modification of Curcumin (CU) combined with the solid lipid nanoparticles (SLN) drug delivery system on anti-tumor activity in vitro. A new structure of Curcumin derivative (CU1) was successfully synthesized by modifying the phenolic hydroxyl group of CU. CU1 was two times more stable than CU at 45 °C or constant light. The SLN containing CU1 (CU1-SLN) was prepared, and the particle size, polydispersity index, entrapment efficiency, drug loading, and zeta potential of CU1-SLN were (104.1 ± 2.43) nm, 0.22 ± 0.008, (95.1 ± 0.38) %, (4.28 ± 0.02) %, and (28.3 ± 1.60) mV, respectively. X-ray diffraction (XRD) and Differential scanning calorimetry (DSC) showed that CU1 is amorphous in SLN. CU1-SLN released the drug slowly for 48 h, while CU and CU1 were released rapidly within 8 h. In terms of cytotoxicity, CU1 exhibited a 1.5-fold higher inhibition than CU against A549 and SMMC-7721 cells, while CU1-SLN showed 2-fold higher inhibition than CU1. Both CU1 and CU1-SLN reduced the toxicity in normal hepatocytes compared with CU (2.6-fold and 12.9-fold, respectively). CU1-SLN showed a significant apoptotic effect (p < 0.05). In summary, CU1 retained the inhibitory effect of CU against tumor cells, while improving stability and safety. Additionally, CU1-SLN presents a promising strategy for the treatment of liver and lung cancer.
Asunto(s)
Antineoplásicos , Curcumina , Nanopartículas , Antineoplásicos/química , Antineoplásicos/farmacología , Curcumina/química , Curcumina/farmacología , Portadores de Fármacos/química , Lípidos/química , Liposomas , Nanopartículas/química , Tamaño de la PartículaRESUMEN
Cancer, which is a leading cause of deaths around the world, is characterized by genetic mutations and epigenetic changes. Baicalin and its aglycone baicalein, the major bioactive flavones derived from the dried root of Scutellaria baicalensis Georigi, belong to flavonoid compounds. Many studies demonstrated that both of them exhibited remarkable promising anticancer activities. This study summarized potential anticancer mechanisms of baicalin and baicalein including induction of apoptosis, initiation of cell cycle arrest, suppression of metastasis, induction of autophagy, and regulation of immunity. Combination strategies involving baicalin or baicalein as chemotherapeutic adjuvants, clinical trial and safety were also discussed. In addition, we compared the difference in their anticancer effects. Interestingly, baicalein showed quicker and stronger inhibitory effects on multiple cancers than those of baicalin, probably due to its smaller size and high lipophilicity which contribute to fast absorption and improve ability to penetrate cells. Taken together, both baicalin and baicalein are effective in treating cancer with good tolerance. However, deglycosylation of baicalin to baicalein was found to have stronger anticancer potential.
Asunto(s)
Flavanonas , Neoplasias , Flavanonas/uso terapéutico , Flavonoides/farmacología , Flavonoides/uso terapéutico , Humanos , Neoplasias/tratamiento farmacológico , Scutellaria baicalensis/metabolismoRESUMEN
The main aim of this study was to improve the therapeutic potential of a paclitaxel (PTX) and curcumin (CU) combination regimen using solid lipid nanoparticles (SLNs). PTX and CU were successfully co-encapsulated at a predetermined ratio in SLNs (PC-SLNs) with high encapsulation efficiency (CU: 97.6%, PTX: 95.8%), appropriate particle size (121.8 ± 1.69 nm), small PDI (0.267 ± 0.023), and negative zeta potential (-30.4 ± 1.25 mV). Compared with PTX or the combination of CU and PTX (CU + PTX), PC-SLNs can greatly reduce the dose of PTX while still achieving the same therapeutic effect on four cancer cell lines, among which the inhibitory effect on A549 lung cancer cells was the strongest. PC-SLNs improved the area under the curve (CU: 1.40-fold; PTX: 2.88-fold), prolonged the residence time (CU: 6.94-fold; PTX: 2.51-fold), and increased the half-life (CU: 5.62-fold; PTX: 6.46-fold), achieving long circulation. PC-SLNs were used to treat lung cancer in a nude mouse xenograft tumor model and the tumor suppression rate reached 78.42%, while those of PTX and (CU + PTX) were 40.53% and 51.56%, respectively. As PC-SLNs can prevent P-glycoprotein efflux, reverse MDR and downregulate the NF-κB pathway. PC-SLNs are a potential antineoplastic agent that is more effective and less toxic in treating lung cancer.
Asunto(s)
Curcumina , Neoplasias Pulmonares , Nanopartículas , Animales , Humanos , Ratones , Línea Celular Tumoral , Curcumina/farmacología , Curcumina/uso terapéutico , Liposomas , Neoplasias Pulmonares/metabolismo , Paclitaxel/farmacología , Paclitaxel/uso terapéuticoRESUMEN
Despite advances in diagnosis and treatment, gastric cancer remains the third most common cause of cancer-related death in humans. The establishment of relevant animal models of gastric cancer is critical for further research. Due to the complexity of the tumor microenvironment and the genetic heterogeneity of gastric cancer, the commonly used preclinical animal models fail to adequately represent clinically relevant models of gastric cancer. However, patient-derived models are able to replicate as much of the original inter-tumoral and intra-tumoral heterogeneity of gastric cancer as possible, reflecting the cellular interactions of the tumor microenvironment. In addition to implanting patient tissues or primary cells into immunodeficient mouse hosts for culture, the advent of alternative hosts such as humanized mouse hosts, zebrafish hosts, and in vitro culture modalities has also facilitated the advancement of gastric cancer research. This review highlights the current status, characteristics, interfering factors, and applications of patient-derived models that have emerged as more valuable preclinical tools for studying the progression and metastasis of gastric cancer.