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1.
Cancers (Basel) ; 16(14)2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39061221

RESUMEN

Curcumin, a polyphenolic compound derived from Curcuma longa, exhibits significant therapeutic potential in cancer management. This review explores curcumin's mechanisms of action, the challenges related to its bioavailability, and its enhancement through modern technology and approaches. Curcumin demonstrates strong antioxidant and anti-inflammatory properties, contributing to its ability to neutralize free radicals and inhibit inflammatory mediators. Its anticancer effects are mediated by inducing apoptosis, inhibiting cell proliferation, and interfering with tumor growth pathways in various colon, pancreatic, and breast cancers. However, its clinical application is limited by its poor bioavailability due to its rapid metabolism and low absorption. Novel delivery systems, such as curcumin-loaded hydrogels and nanoparticles, have shown promise in improving curcumin bioavailability and therapeutic efficacy. Additionally, photodynamic therapy has emerged as a complementary approach, where light exposure enhances curcumin's anticancer effects by modulating molecular pathways crucial for tumor cell growth and survival. Studies highlight that combining low concentrations of curcumin with visible light irradiation significantly boosts its antitumor efficacy compared to curcumin alone. The interaction of curcumin with cytochromes or drug transporters may play a crucial role in altering the pharmacokinetics of conventional medications, which necessitates careful consideration in clinical settings. Future research should focus on optimizing delivery mechanisms and understanding curcumin's pharmacokinetics to fully harness its therapeutic potential in cancer treatment.

2.
Front Oncol ; 14: 1402483, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38835386

RESUMEN

Gastric Cancer (GC) is a prevalent malignancy globally and is the third leading cause of cancer-related deaths. Recent researches focused on the correlation between intestinal flora and GC. Studies indicate that bacteria can influence the development of gastrointestinal tumors by releasing bacterial extracellular vesicles (BEVs). The Tumor microenvironment (TME) plays an important role in tumor survival, with the interaction between intestinal flora, BEVs, and TME directly impacting tumor progression. Moreover, recent studies have demonstrated that intestinal microflora and BEVs can modify TME to enhance the effectiveness of antitumor drugs. This review article provides an overview and comparison of the biological targets through which the intestinal microbiome regulates TME, laying the groundwork for potential applications in tumor diagnosis, treatment, and prognosis.

3.
Pharmacol Ther ; 260: 108672, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38838821

RESUMEN

The antitumor antibiotic mithramycin A (MTA) binds to G/C-rich DNA sequences in the presence of dications. MTA inhibits transcription regulated by the Sp1 transcription factor, often enhanced during tumor development. It shows antitumor activity, but its clinical use was discontinued due to toxic side effects. However, recent observations have led to its use being reconsidered. The MTA biosynthetic pathways have been modified to produce mithramycin analogs (mithralogs) that encompass lower toxicity and improved pharmacological activity. Some mithralogs reduce gene expression in human ovarian and prostate tumors, among other types of cancer. They down-regulate gene expression in various cellular processes, including Sp1-responsive genes that control tumor development. Moreover, MTA and several mithralogs, such as EC-8042 (DIG-MSK) and EC-8105, effectively treat Ewing sarcoma by inhibiting transcription controlled by the oncogenic EWS-FLI1 transcription factor.


Asunto(s)
Neoplasias , Plicamicina , Humanos , Plicamicina/análogos & derivados , Plicamicina/farmacología , Plicamicina/uso terapéutico , Animales , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Antibióticos Antineoplásicos/farmacología , Antibióticos Antineoplásicos/uso terapéutico , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico
4.
J Gastrointest Oncol ; 15(1): 63-85, 2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38482233

RESUMEN

Background: The discovery of biomarkers has facilitated the treatment of cancer. At present, the relationship between activin A receptor type-1 (ACVR1) and gastric cancer is gradually discovered. The aim of this study was to explore the expression of ACVR1 in gastric cancer and its clinical significance, to study the relationship between ACVR1 and tumor microenvironment (TME) for the prognosis of gastric cancer, and to further identify new targets for immunotherapy in gastric cancer. Methods: ACVR1 was first selected as a study gene according to several cancer and gastric cancer public datasets. Its pancancer expression was explored using the UCSC Xena database. The expression level, prognosis, and clinicopathological features of ACVR1 in gastric cancer were analyzed using The Cancer Genome Atlas (TCGA) database. Immunohistochemistry (IHC)-based experiments were conducted to study the expression of ACVR1 at the protein level. The IHC data were analyzed for correlations between ACVR1 expression and various clinicopathological factors and prognosis. The correlation of this gene with the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, immune infiltration, immune checkpoints, drug therapy, tumor mutation burden (TMB), microsatellite instability (MSI), and mismatch repair (MMR) system was analyzed using R software. Results: TCGA data showed that the expression of ACVR1 was higher in gastric cancer tissues than in paracancerous tissues. Moreover, the IHC experiments indicated that ACVR1 was upregulated in gastric cancer tissues at the protein level. Both univariate Cox and multivariate Cox results showed that the increase of ACVR1 was closely associated with tumor stage, size, lymph node metastasis, and age. High ACVR1 expression was linked to a poor prognosis of gastric cancer. The results also revealed that ACVR1 was closely related to suppressive immune cells and pathways. Analyses of immune checkpoints, antitumor drug, TMB, and immune microenvironment indicated that ACVR1 had an antitumor immune effect, promoting gastric cancer development and leading to poor immunotherapy. Conclusions: High ACVR1 expression can be used as an independent prognostic factor to predict the prognostic survival of patients with gastric cancer. ACVR1 expression in gastric cancer tissues was significantly correlated with immune infiltration and may thus serve as a potential therapeutic target for gastric cancer immunotherapy.

5.
Clin Chem Lab Med ; 62(2): 293-302, 2024 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-37606251

RESUMEN

OBJECTIVES: Accumulating evidence argues for a more widespread use of therapeutic drug monitoring (TDM) to support individualized medicine, especially for therapies where toxicity and efficacy are critical issues, such as in oncology. However, development of TDM assays struggles to keep pace with the rapid introduction of new drugs. Therefore, novel approaches for faster assay development are needed that also allow effortless inclusion of newly approved drugs as well as customization to smaller subsets if scientific or clinical situations require. METHODS: We applied and evaluated two machine-learning approaches i.e., a regression-based approach and an artificial neural network (ANN) to retention time (RT) prediction for efficient development of a liquid chromatography mass spectrometry (LC-MS) method quantifying 73 oral antitumor drugs (OADs) and five active metabolites. Individual steps included training, evaluation, comparison, and application of the superior approach to RT prediction, followed by stipulation of the optimal gradient. RESULTS: Both approaches showed excellent results for RT prediction (mean difference ± standard deviation: 2.08 % ± 9.44 % ANN; 1.78 % ± 1.93 % regression-based approach). Using the regression-based approach, the optimum gradient (4.91 % MeOH/min) was predicted with a total run time of 17.92 min. The associated method was fully validated following FDA and EMA guidelines. Exemplary modification and application of the regression-based approach to a subset of 14 uro-oncological agents resulted in a considerably shortened run time of 9.29 min. CONCLUSIONS: Using a regression-based approach, a multi drug LC-MS assay for RT prediction was efficiently developed, which can be easily expanded to newly approved OADs and customized to smaller subsets if required.


Asunto(s)
Antineoplásicos , Humanos , Cromatografía Liquida/métodos , Espectrometría de Masas en Tándem/métodos , Antineoplásicos/farmacología , Monitoreo de Drogas/métodos , Aprendizaje Automático
6.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1013594

RESUMEN

Platelets have long been recognized as key players in hemostasis and thrombosis; however, there is growing evidence that they are also involved in cancer. Preclinical and clinical studies have shown that platelets can promote tumorigenesis and metastasis through various crosstalks between platelets and cancer cells. Platelets play an active role in all stages of tumorigenesis, including tumor growth, tumor cell extravasation, and metastasis. In addition, thrombocytosis in cancer patients is associated with poor patient survival. Platelets are also well-placed to coordinate local and distant tumor-host interactions due to the a- bundance of microparticles and exosomes. Therefore, antitumor drugs targeting platelets have great development and application prospects. The following will review the research progress of anti-tumor drugs targeting platelets.

7.
J Microencapsul ; : 1-19, 2023 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-37824702

RESUMEN

The present study was aimed to prepare and examine in vitro novel dual-drug loaded delivery systems. Biodegradable nanoparticles based on poly(L-glutamic acid-co-D-phenylalanine) were used as nanocarriers for encapsulation of two drugs from the paclitaxel, irinotecan, and doxorubicin series. The developed delivery systems were characterised with hydrodynamic diameters less than 300 nm (PDI < 0.3). High encapsulation efficiencies (≥75%) were achieved for all single- and dual-drug formulations. The release studies showed faster release at acidic pH, with the release rate decreasing over time. The release patterns of the co-encapsulated forms of substances differed from those of the separately encapsulated drugs, suggesting differences in drug-polymer interactions. The joint action of encapsulated drugs was analysed using the colon cancer cells, both for the dual-drug delivery sytems and a mixture of single-drug formulations. The encapsulated forms of the drug combinations demonstrated comparable efficacy to the free forms, with the encapsulation enhancing solubility of the hydrophobic drug paclitaxel.

8.
Curr Pharm Des ; 29(22): 1747-1774, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37559240

RESUMEN

BACKGROUND: Cisplatin, a platinum complex discovered by Rosenberg in 1969, has long been known as the first metal-based anticancer agent. Since then, various similar derivatives of cisplatin have been investigated for pharmacological activity, and the approved complexes have been applied as drugs. OBJECTIVES: The aims of the current study are: 1) to summarize the advantages and dose-limiting effects of the approved and unapproved chemotherapy platinum cytostatics, 2) to develop new strategies for the development of platinum anticancer drugs, and 3) to clarify the important factors for the mechanism of action of platinum complexes. METHODS: A search was conducted in the literature databases, and the obtained information was summarized and analyzed. RESULTS: Myelosuppression is the main dose-limiting effect and the reason for the disapproval of platinum complexes, such as picoplatin, enloplatin, miboplatin, sebriplatin, zeniplatin, spiroplatin, iproplatin, and ormaplatin. From the basic point of view of inorganic coordination chemistry, such as theoretical calculations, crystal structures of model complexes, docking structures with nucleic acid molecules, spectroscopy, and biological aspects, the importance of physicochemical properties of inorganic platinum complexes for their mechanism of action has been indicated. Spectroscopic methods, such as FTIR, NMR, X-ray crystal structure analysis, and fluorescence microscopy, are important for the investigation of the conformational changes in the binding of platinum complexes and DNA. CONCLUSION: In the development of platinum complexes, strong anti-cancer drug activity, low toxicity, and resistance can be obtained by the application of polynuclear platinum agents, complexes with targeted activity, and nanoparticle formulations. Electronic structure, stereochemical, and thermodynamic properties are essential for understanding the reaction mechanism of platinum complexes.

9.
Materials (Basel) ; 16(11)2023 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-37297151

RESUMEN

Interest in calcium phosphate cements as materials for the restoration and treatment of bone tissue defects is still high. Despite commercialization and use in the clinic, the calcium phosphate cements have great potential for development. Existing approaches to the production of calcium phosphate cements as drugs are analyzed. A description of the pathogenesis of the main diseases of bone tissue (trauma, osteomyelitis, osteoporosis and tumor) and effective common treatment strategies are presented in the review. An analysis of the modern understanding of the complex action of the cement matrix and the additives and drugs distributed in it in relation to the successful treatment of bone defects is given. The mechanisms of biological action of functional substances determine the effectiveness of use in certain clinical cases. An important direction of using calcium phosphate cements as a carrier of functional substances is the volumetric incorporation of anti-inflammatory, antitumor, antiresorptive and osteogenic functional substances. The main functionalization requirement for carrier materials is prolonged elution. Various release factors related to the matrix, functional substances and elution conditions are considered in the work. It is shown that cements are a complex system. Changing one of the many initial parameters in a wide range changes the final characteristics of the matrix and, accordingly, the kinetics. The main approaches to the effective functionalization of calcium phosphate cements are considered in the review.

10.
Int J Mol Sci ; 24(12)2023 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-37372996

RESUMEN

In this work, we elucidated some key aspects of the mechanism of action of the cisplatin anticancer drug, cis-[Pt(NH3)2Cl2], involving direct interactions with free nucleotides. A comprehensive in silico molecular modeling analysis was conducted to compare the interactions of Thermus aquaticus (Taq) DNA polymerase with three distinct N7-platinated deoxyguanosine triphosphates: [Pt(dien)(N7-dGTP)] (1), cis-[Pt(NH3)2Cl(N7-dGTP)] (2), and cis-[Pt(NH3)2(H2O)(N7-dGTP)] (3) {dien = diethylenetriamine; dGTP = 5'-(2'-deoxy)-guanosine-triphosphate}, using canonical dGTP as a reference, in the presence of DNA. The goal was to elucidate the binding site interactions between Taq DNA polymerase and the tested nucleotide derivatives, providing valuable atomistic insights. Unbiased molecular dynamics simulations (200 ns for each complex) with explicit water molecules were performed on the four ternary complexes, yielding significant findings that contribute to a better understanding of experimental results. The molecular modeling highlighted the crucial role of a specific α-helix (O-helix) within the fingers subdomain, which facilitates the proper geometry for functional contacts between the incoming nucleotide and the DNA template needed for incorporation into the polymerase. The analysis revealed that complex 1 exhibits a much lower affinity for Taq DNA polymerase than complexes 2-3. The affinities of cisplatin metabolites 2-3 for Taq DNA polymerase were found to be quite similar to those of natural dGTP, resulting in a lower incorporation rate for complex 1 compared to complexes 2-3. These findings could have significant implications for the cisplatin mechanism of action, as the high intracellular availability of free nucleobases might promote the competitive incorporation of platinated nucleotides over direct cisplatin attachment to DNA. The study's insights into the incorporation of platinated nucleotides into the Taq DNA polymerase active site suggest that the role of platinated nucleotides in the cisplatin mechanism of action may have been previously underestimated.


Asunto(s)
Cisplatino , Guanina , Cisplatino/farmacología , Polimerasa Taq , Simulación de Dinámica Molecular , ADN/química , Nucleótidos
11.
Int J Mol Sci ; 24(8)2023 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-37108074

RESUMEN

The aim of this study was to develop an innovative, dual-stimuli-responsive smart hydrogel local drug delivery system (LDDS), potentially useful as an injectable simultaneous chemotherapy and magnetic hyperthermia (MHT) antitumor treatment device. The hydrogels were based on a biocompatible and biodegradable poly(ε-caprolactone-co-rac-lactide)-b-poly(ethylene glycol)-b-poly(ε-caprolactone-co-rac-lactide) (PCLA-PEG-PCLA, PCLA) triblock copolymer, synthesized via ring-opening polymerization (ROP) in the presence of a zirconium(IV) acetylacetonate (Zr(acac)4) catalyst. The PCLA copolymers were successfully synthesized and characterized using NMR and GPC techniques. Furthermore, the gel-forming and rheological properties of the resulting hydrogels were thoroughly investigated, and the optimal synthesis conditions were determined. The coprecipitation method was applied to create magnetic iron oxide nanoparticles (MIONs) with a low diameter and a narrow size distribution. The magnetic properties of the MIONs were close to superparamagnetic upon TEM, DLS, and VSM analysis. The particle suspension placed in an alternating magnetic field (AMF) of the appropriate parameters showed a rapid increase in temperature to the values desired for hyperthermia. The MIONs/hydrogel matrices were evaluated for paclitaxel (PTX) release in vitro. The release was prolonged and well controlled, displaying close to zero-order kinetics; the drug release mechanism was found to be anomalous. Furthermore, it was found that the simulated hyperthermia conditions had no effect on the release kinetics. As a result, the synthesized smart hydrogels were discovered to be a promising antitumor LDDS, allowing simultaneous chemotherapy and hyperthermia treatment.


Asunto(s)
Hidrogeles , Nanopartículas de Magnetita , Hidrogeles/química , Poliésteres/química , Polietilenglicoles/química , Polímeros/química , Sistemas de Liberación de Medicamentos , Temperatura
12.
Pharmaceutics ; 15(3)2023 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-36986802

RESUMEN

Nucleoside analogues (NAs) are a family of compounds which include a variety of purine and pyrimidine derivatives, widely used as anticancer and antiviral agents. For their ability to compete with physiological nucleosides, NAs act as antimetabolites exerting their activity by interfering with the synthesis of nucleic acids. Much progress in the comprehension of their molecular mechanisms has been made, including providing new strategies for potentiating anticancer/antiviral activity. Among these strategies, new platinum-NAs showing a good potential to improve the therapeutic indices of NAs have been synthesized and studied. This short review aims to describe the properties and future perspectives of platinum-NAs, proposing these complexes as a new class of antimetabolites.

13.
Med Res Rev ; 43(1): 212-236, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36029178

RESUMEN

The cost of antitumor drug development is enormous, yet the clinical outcomes are less than satisfactory. Therefore, it is of great importance to develop effective drug screening methods that enable accurate, rapid, and high-throughput discovery of lead compounds in the process of preclinical antitumor drug research. An effective solution is to use the patient-derived xenograft (PDX) tumor animal models, which are applicable for the elucidation of tumor pathogenesis and the preclinical testing of novel antitumor compounds. As a promising screening model organism, zebrafish has been widely applied in the construction of the PDX tumor model and the discovery of antineoplastic agents. Herein, we systematically survey the recent cutting-edge advances in zebrafish PDX models (zPDX) for studies of pathogenesis mechanisms and drug screening. In addition, the techniques used in the construction of zPDX are summarized. The advantages and limitations of the zPDX are also discussed in detail. Finally, the prospects of zPDX in drug discovery, translational medicine, and clinical precision medicine treatment are well presented.


Asunto(s)
Antineoplásicos , Neoplasias , Animales , Humanos , Pez Cebra , Ensayos Antitumor por Modelo de Xenoinjerto , Xenoinjertos , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Modelos Animales de Enfermedad
14.
Artículo en Español | LILACS-Express | LILACS | ID: biblio-1450095

RESUMEN

Introducción: El cáncer de ovario es uno de los tumores más frecuentes y letales entre las mujeres. Esto se debe a su detección en estados tardíos y al desarrollo de quimiorresistencia a la terapia estándar. El desarrollo de terapias dirigidas contra las propiedades distintivas de las células cancerosas y sus características habilitadoras ha surgido como una alternativa promisoria para el tratamiento de estos tumores. Objetivo: Describir las actuales estrategias terapéuticas dirigidas contra las distintas capacidades de las células tumorales en el tratamiento del cáncer de ovario. Método: Se realizó una búsqueda en las bases de datos ScienceDirect, Redalyc, Latindex, ResearchGate, PubMed, Elsevier, ClinicalTrials.gov, SpringerLink, LARVOL´s CLIN, Registro Público Cubano de Ensayos Clínicos, entre enero y abril de 2023. Se seleccionaron 50 artículos referentes al cáncer de ovario y las alternativas para su tratamiento. Desarrollo: Se mencionaron los diversos factores que influyen en la elección de terapias contra el cáncer de ovario. Se describieron las actuales dianas terapéuticas utilizadas en el tratamiento de esta neoplasia, así como el empleo de múltiples fármacos aprobados y en fases de estudio, y las combinaciones sinérgicas de los mismos. Consideraciones finales: Actualmente existen disímiles opciones de tratamiento del cáncer de ovario. A pesar de que la eficacia clínica de los agentes dirigidos todavía está restringida a subtipos moleculares específicos y ningún ensayo ilustra un beneficio en la supervivencia general, son notorios los resultados alcanzados en el desarrollo de fármacos específicamente dirigidos contra la inestabilidad del genoma y angiogénesis sostenida.


Introduction: Ovarian cancer is one of the most common and lethal tumor in women. This happens as a result of late-stage cancer detention and an increased chemoresistance to standard therapy. The current development in therapies to kill the cancer cells and its spread tendencies has emerged as a key alternative to treat tumors. Objective: To describe the current therapeutic strategies lead to confront different capabilities of tumor cells found in the ovarian cancer treatment. Method: A search of literuture was carried out in the following databases ScienceDirect, Redalyc, Latindex, ResearchGate, PubMed, Elsevier, ClinicalTrials.gov, SpringerLink, LARVOL's CLIN, Cuban Public Registry of Clinical Trials, from January to April 2023. A total of 50 text concerning ovarian cancer subject and alternative for treatment were selected. Development: The driving factors that promoted the use of ovarian cancer therapies were pointed out. The current therapeutic targets used in the treatment of this neoplasia were described, as well as the use of multiple approved drugs or in process of approval, including the synergistic drug combinations. Final considerations: There are a lot of options currently being implemented in ovarian cancer treatment. Despite clinical efficacy of targeted therapy, it´s presented still restricted to specific molecular subtypes and none of the assays illustrated survival benefit in general; the results obtained in the process of drugs development specifically targeting genome instability and sustained angiogenesis have been remarkable.


Introdução: O câncer de ovário é um dos tumores mais frequentes e letais entre as mulheres. Isso se deve à sua detecção em estágios tardios e ao desenvolvimento de quimiorresistência à terapia padrão. O desenvolvimento de terapias direcionadas contra as propriedades distintas das células cancerígenas e suas características facilitadoras surgiu como uma alternativa promissora para o tratamento desses tumores. Objetivo: Descrever as atuais estratégias terapêuticas dirigidas contra as diferentes capacidades das células tumorais no tratamento do câncer de ovário. Método: Foi realizada uma busca nas bases de dados ScienceDirect, Redalyc, Latindex, ResearchGate, PubMed, Elsevier, ClinicalTrials.gov, SpringerLink, LARVOL's CLIN, Registro Público Cubano de Ensaios Clínicos, entre janeiro e abril de 2023. 50 artigos referentes ao câncer de ovário e as alternativas para o seu tratamento. Desenvolvimento: Foram mencionados os vários fatores que influenciam a escolha das terapias contra o câncer de ovário. Foram descritos os atuais alvos terapêuticos utilizados no tratamento desta neoplasia, bem como o uso de múltiplas drogas aprovadas e em fase de estudo, e suas combinações sinérgicas. Considerações finais: Atualmente existem opções de tratamento dissimilares para o câncer de ovário. Apesar de a eficácia clínica dos agentes direcionados ainda estar restrita a subtipos moleculares específicos e nenhum ensaio mostrar benefício na sobrevida global, são notáveis os resultados alcançados no desenvolvimento de fármacos direcionados especificamente contra a instabilidade do genoma e a angiogênese sustentada.

15.
Front Pharmacol ; 13: 1065701, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36532719

RESUMEN

Cervical cancer (CC) is the fourth leading gynecological malignancy in females worldwide. Cuproptosis, a form of cell death induced by copper, elicits a novel therapeutic strategy in anticancer therapy. Nonetheless, the effects of cuproptosis-related lncRNAs in CC remain unclear. Therefore, we aim to investigate cuproptosis-related lncRNAs, develop a risk model for prognostic prediction, and elucidate the immunological profile of CC. Transcription profiles and clinical follow-up data of CC were retrieved from The Cancer Genome Atlas (TCGA) database. Afterward, the risk model was built by distinguishing prognostic cuproptosis-related lncRNAs using the least absolute shrinkage and selection operator (LASSO) Cox regression. The correctness of the risk model was validated, and a nomogram was established followed by tumor immune microenvironment analysis. Tumor immune dysfunction and exclusion (TIDE) scores were used to assess immunotherapy response, and anticancer pharmaceutical half-maximal inhibitory concentration (IC50) prediction was performed for potential chemotherapy medicines. Finally, through coexpression analysis, 199 cuproptosis-related lncRNAs were collected. A unique risk model was generated using 6 selected prognostic cuproptosis-related lncRNAs. The risk score performed a reliable independent prediction of CC survival with higher diagnostic effectiveness compared to generic clinical characteristics. Immunological cell infiltration investigation indicated that the risk model was substantially linked with CC patients' immunology, and the low-risk patients had lower TIDE scores and increased checkpoint expression, suggesting a stronger immunotherapy response. Besides, the high-risk group exhibited distinct sensitivity to anticancer medications. The immune-related progression was connected to the differentially expressed genes (DEGs) between risk groups. Generally, the risk model comprised 6 cuproptosis-related lncRNAs that may help predict CC patients' overall survival, indicate immunocyte infiltration, and identify individualized treatment.

16.
Cell Biosci ; 12(1): 165, 2022 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-36182930

RESUMEN

Since an outbreak started in China in 2019, coronavirus disease 2019 (COVID-19) has rapidly become a worldwide epidemic with high contagiousness and caused mass mortalities of infected cases around the world. Currently, available treatments for COVID-19, including supportive care, respiratory support and antiviral therapy, have shown limited efficacy. Thus, more effective therapeutic modalities are highly warranted. Drug repurposing, as an efficient strategy to explore a potential broader scope of the application of approved drugs beyond their original indications, accelerates the process of discovering safe and effective agents for a given disease. Since the outbreak of COVID-19 pandemic, drug repurposing strategy has been widely used to discover potential antiviral agents, and some of these drugs have advanced into clinical trials. Antitumor drugs compromise a vast variety of compounds and exhibit extensive mechanism of action, showing promising properties in drug repurposing. In this review, we revisit the potential value of antitumor drugs in the treatment of COVID-19 and systematically discuss their possible underlying mechanisms of the antiviral actions.

17.
Front Bioeng Biotechnol ; 10: 1021966, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36246388

RESUMEN

Traditional tumor models cannot perfectly simulate the real state of tumors in vivo, resulting in the termination of many clinical trials. 3D tumor models' technology provides new in vitro models that bridge the gap between in vitro and in vivo findings, and organoids maintain the properties of the original tissue over a long period of culture, which enables extensive research in this area. In addition, they can be used as a substitute for animal and in vitro models, and organoids can be established from patients' normal and malignant tissues, with unique advantages in clinical drug development and in guiding individualized therapies. 3D tumor models also provide a promising platform for high-throughput research, drug and toxicity testing, disease modeling, and regenerative medicine. This report summarizes the 3D tumor model, including evidence regarding the 3D tumor cell culture model, 3D tumor slice model, and organoid culture model. In addition, it provides evidence regarding the application of 3D tumor organoid models in precision oncology and drug screening. The aim of this report is to elucidate the value of 3D tumor models in cancer research and provide a preclinical reference for the precise treatment of cancer patients.

18.
Eur J Med Chem ; 243: 114680, 2022 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-36152386

RESUMEN

Platinum-based antitumor drugs have been used in many types of tumors due to its broad antitumor spectrum in clinic. Encouraged by the cisplatin's (CDDP) worldwide success in cancer chemotherapy, the research in platinum-based antitumor drugs has evolved from traditional platinum drug to multi-ligand and multifunctional platinum prodrugs over half a century. With the rapid development of metal drugs and the anticancer immune response, challenges and opportunities in platinum drug research have been shifted from traditional platinum-based drugs to platinum-based hybrids and the direction of development is tending toward photodynamic therapy, nano-delivery therapy, drug combination, targeted therapy, diagnostic therapy, immune-combination therapy and tumor stem cell therapy. In this review, we first exhaustively overviewed the role of platinum-based antitumor prodrugs and the anticancer immune response in medicinal inorganic chemistry based on the special nanomaterials, the modification of specific ligands, and the multiple functions obtained that are beneficial for tumor therapy in the last five years. We also categorized them according to drug potency and function. There hasn't been a comprehensive evaluation of precursor platinum drugs in prior articles. And a multifarious approach to distinguish and detail the variety of alterations of platinum-based precursors in various valence states also hasn't been summarized. In addition, this review points out the main problems at the interface of chemistry, biology, and medicine from their action mechanisms for current platinum drug development, and provides up-to-date potential strategies from drug design perspectives to circumvent those drawbacks. And a promising idea is also enlightened for researchers in the development and discovery of platinum prodrugs.


Asunto(s)
Antineoplásicos , Neoplasias , Profármacos , Humanos , Platino (Metal)/uso terapéutico , Profármacos/farmacología , Profármacos/uso terapéutico , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Neoplasias/tratamiento farmacológico , Química Inorgánica , Ligandos , Inmunidad
19.
Zhongguo Fei Ai Za Zhi ; 25(7): 541-545, 2022 Jul 20.
Artículo en Chino | MEDLINE | ID: mdl-35899454

RESUMEN

In 2019, Drug Administration Law of China was first time proposed that the country should establish pharmacovigilance system. In 2021, the first Pharmacovigilance Quality Management Standard of China was released. The proposal and implementation of pharmacovigilance were the initial stage in China, and it needed to improve the aspects of pharmacovigilance include institution, monitoring mechanism and database construction. The number of new diagnosed cancer patients in China ranked first in the world. In recent years, the marketing speed of novel antitumor drugs was accelerated, and there were many clinical trials. Therefore, antitumor pharmacovigilance was imperative. In this article, we summarized pharmacovigilance of the origin, clinical practice objectives, procedures, methods. We described the difficulties in antitumor pharmacovigilance and current characteristics of pharmacovigilance in China, aiming to provide reference for the development of antitumor pharmacovigilance.
.


Asunto(s)
Neoplasias Pulmonares , Farmacovigilancia , China , Humanos
20.
J Hematol Oncol ; 15(1): 89, 2022 07 07.
Artículo en Inglés | MEDLINE | ID: mdl-35799213

RESUMEN

Vascular endothelial growth factor receptors (VEGFRs) are a family of receptor protein tyrosine kinases that play an important role in the regulation of tumor-induced angiogenesis. Currently, VEGFR inhibitors have been widely used in the treatment of various tumors. However, current VEGFR inhibitors are limited to a certain extent due to limited clinical efficacy and potential toxicity, which hinder their clinical application. Thus, the development of new strategies to improve the clinical outcomes and minimize the toxic effects of VEGFR inhibitors is required. Given the synergistic effect of VEGFR and other therapies in tumor development and progression, VEGFR dual-target inhibitors are becoming an attractive approach due to their favorable pharmacodynamics, low toxicity, and anti-resistant effects. This perspective provides an overview of the development of VEGFR dual-target inhibitors from multiple aspects, including rational target combinations, drug discovery strategies, structure-activity relationships and future directions.


Asunto(s)
Inhibidores de la Angiogénesis , Neoplasias , Inhibidores de Proteínas Quinasas , Receptores de Factores de Crecimiento Endotelial Vascular , Inhibidores de la Angiogénesis/farmacología , Inhibidores de la Angiogénesis/uso terapéutico , Humanos , Neoplasias/tratamiento farmacológico , Neovascularización Patológica/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Receptores de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores
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