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1.
Bone Joint J ; 102-B(2): 177-185, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32009426

RESUMEN

AIMS: To investigate the benefits of denosumab in combination with nerve-sparing surgery for treatment of sacral giant cell tumours (GCTs). METHODS: This is a retrospective cohort study of patients with GCT who presented between January 2011 and July 2017. Intralesional curettage was performed and patients treated from 2015 to 2017 also received denosumab therapy. The patients were divided into three groups: Cohort 1: control group (n = 36); cohort 2: adjuvant denosumab group (n = 9); and cohort 3: neo- and adjuvant-denosumab group (n = 17). RESULTS: There were 68 patients within the study period. Six patients were lost to follow-up. The mean follow-up was 47.7 months (SD 23.2). Preoperative denosumab was found to reduce intraoperative haemorrhage and was associated with shorter operating time for tumour volume > 200 cm3. A total of 17 patients (27.4%) developed local recurrence. The locoregional control rate was 77.8% (7/9) and 87.5% (14/16) respectively for cohorts 2 and 3, in comparison to 66.7% (24/36) of the control group. The recurrence-free survival (RFS) rate was significantly higher for adjuvant denosumab group versus those without adjuvant denosumab during the first two years: 100% vs 83.8% at one year and 95.0% vs 70.3% at two years. No significant difference was found for the three-year RFS rate. CONCLUSION: Preoperative denosumab therapy was found to reduce intraoperative haemorrhage and was associated with shorter operating times. Adjuvant denosumab was useful to prevent early recurrence during the first two years after surgery. Cite this article: Bone Joint J 2020;102-B(2):177-185.


Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias Óseas/cirugía , Denosumab/uso terapéutico , Tumor Óseo de Células Gigantes/cirugía , Sacro/cirugía , Adolescente , Adulto , Neoplasias Óseas/tratamiento farmacológico , Niño , Terapia Combinada , Legrado/métodos , Femenino , Tumor Óseo de Células Gigantes/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto Joven
3.
Medicine (Baltimore) ; 99(5): e18646, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32000369

RESUMEN

INTRODUCTION: Clear cell adenocarcinoma of the cervix (CCAC), a rare and more severe type of gynecological cancer, is especially rare in pediatric patients. Traditionally, surgery following chemotherapy (CT) and radiation therapy is the preferred treatment for CCAC; however, patients have poor 5-year survival rates than other types of cervical cancers. PATIENT CONCERNS: A 6-year-old girl with a history of vaginal discharge for 18 months was diagnosed with CCAC by histological examination. Her parents refused the traditional treatment of radical hysterectomy and lymph node dissection because of her young age. DIAGNOSIS: The patient's tests revealed negative human papilloma virus and negative methylated paired box 1 gene results. The tumor mass histopathology revealed stage IIA1 CCAC that originated from the cervix. INTERVENTIONS: Tumor mass excision with preservation of the cervix by electrosurgical biopsy under hysteroscopy was performed. Four cycles of docetaxel and oxaliplatin CT were administered every 3 weeks. OUTCOMES: No signs of recurrence were observed in the 28 months after final treatment and diagnosis on magnetic resonance imaging, color ultrasonic imaging, and gynecological examination. Serologic tumor biomarkers were also within normal ranges. CONCLUSIONS: This is the first reported CCAC case in which the primary treatment included electrosurgical biopsy of the polypoid mass under hysteroscopy, followed by CT without traditional treatment: radical surgery with pelvic and/or lymphadenectomy for fertility preservation. This is a new treatment approach for young CCAC patients without the use of surgery.


Asunto(s)
Adenocarcinoma/cirugía , Histeroscopía , Tratamientos Conservadores del Órgano , Neoplasias del Cuello Uterino/cirugía , Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/patología , Antineoplásicos/uso terapéutico , Cuello del Útero/patología , Niño , Docetaxel/uso terapéutico , Femenino , Humanos , Oxaliplatino/uso terapéutico , Neoplasias del Cuello Uterino/diagnóstico por imagen , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/patología
4.
Medicine (Baltimore) ; 99(5): e18701, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32000374

RESUMEN

INTRODUCTION: Programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors have been increasingly used in the treatment of cancer. Immunosuppressive therapy can control the cancer well and is suitable for the moderate to severe diseases. However, according to clinical observation, immune-related cardiac adverse events against PD-1or/and PD-L1 are inevitable, but generally reversible. Understanding the cardiac adverse events of PD-1 or/and PD-L1 inhibitors is crucial to improve the anti-cancer efficacy and ensure the life safety of patients. The variability of cardiac adverse events between different immunosuppressants and different cancers is not clear. METHODS AND ANALYSIS: This protocol established in this study has been reported following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. We will search the following electronic bibliographic databases: PubMed, Cochrane Library, EMBASE databases and ClinicalTrials.gov from their inception to December 2019. We will use a combination of Medical Subject Heading, and free-text terms with various synonyms to search based on the Eligibility criteria. We will include RCTs on PD-1 or/and PD-L1 inhibitors therapy to analyze. In addition, our study will include some clinical trials. All relevant RCTs will be included, such as early phase I/II, phase III experimental trials, prospective and retrospective observational studies. According to the inclusion and exclusion criteria outlined above, the full texts of each eligible study will be retrieved for further identification by one reviewer. Two authors will screen the titles and abstracts of all records retrieved in above electronic databases independently to find potentially eligible reviews. Data will be extracted by 2 reviewers independently using a pre-designed data extraction form. The other reviewer will validate data. I-square (I) test, substantial heterogeneity, sensitivity analysis and publication bias assessment will be performed accordingly. For our network meta-analysis, we will use Stata 15.0 and WinBUGS 1.4.3. ETHICS AND DISSEMINATION: Ethics approval and patient consent would be not required because the data of this network meta-analysis mainly are obtained from existing resources. This network meta-analysis will be published in a peer-reviewed journal. PROSPERO NUMBER: CRD42019142865.


Asunto(s)
Antineoplásicos/efectos adversos , Antígeno B7-H1/antagonistas & inhibidores , Cardiopatías/inducido químicamente , Neoplasias/tratamiento farmacológico , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Humanos , Metaanálisis como Asunto , Revisiones Sistemáticas como Asunto
5.
Medicine (Baltimore) ; 99(5): e18811, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32000382

RESUMEN

RATIONALE: Concurrent calreticulin (CALR) mutation and BCR-ABL1 fusion are extremely rare in chronic myelogenous leukemia; to date, only 12 cases have been reported. PATIENT CONCERNS: A 57-year-old male who had an 11-year history of essential thrombocytosis presented to our hospital with leukocytosis and marked splenomegaly for 3 months. DIAGNOSES: Chronic myelogenous leukemia with myeloid fibrosis arising on the background of essential thrombocytosis harboring both BCR-ABL1 fusion and type-1 like CALR mutation. INTERVENTIONS: Imatinib was started at 300 mg daily and increased to 400 mg daily after 3 months; interferon was added after 12 months. OUTCOMES: Partial cytogenetic response was achieved after 3 months of imatinib therapy and complete cytogenetic response was achieved after 1 year of treatment. However, CALR mutation was still present with a stable mutational allele burden. LESSONS: In this case report and review of additional 12 cases with simultaneous presence of CALR-mutation and BCR-ABL1 fusion, we highlighted the importance of integrating clinical, morphological, and molecular genetic data for classifying atypical myeloid neoplasms.


Asunto(s)
Calreticulina/genética , Proteínas de Fusión bcr-abl/genética , Genes abl , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Trombocitemia Esencial/genética , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Humanos , Mesilato de Imatinib/farmacología , Mesilato de Imatinib/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Trombocitemia Esencial/complicaciones
6.
Lancet Haematol ; 7(2): e168-e176, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32004486

RESUMEN

Tumour lysis syndrome is a complication of chemotherapy for haematological malignancies; in particular, aggressive leukaemias and lymphomas. For haematological malignancies, targeted therapies, such as small molecule inhibitors and monoclonal antibodies, have a high anti-tumour activity, are well tolerated, and have a low incidence of associated tumour lysis syndrome. The BCL-2 inhibitor venetoclax has a high anti-tumour activity in chronic lymphocytic leukaemia, achieving deep remissions by potently inducing apoptosis and increasing the risk for tumour lysis syndrome. In this Viewpoint, we discuss the pathophysiology, risk factors, monitoring, changes in laboratory parameters, and clinical manifestations of tumour lysis syndrome, and the prophylaxis and treatments available for this complication. Prophylaxis and treatment strategies have been implemented as standard of care in patients receiving venetoclax to minimise the risk of both laboratory and clinical manifestations of tumour lysis syndrome.


Asunto(s)
Antineoplásicos/efectos adversos , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Terapia Molecular Dirigida/efectos adversos , Proteínas de Neoplasias/antagonistas & inhibidores , Inhibidores de Proteínas Quinasas/efectos adversos , Proteínas Proto-Oncogénicas c-bcl-2/antagonistas & inhibidores , Síndrome de Lisis Tumoral/etiología , Lesión Renal Aguda/etiología , Lesión Renal Aguda/terapia , Alopurinol/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Arritmias Cardíacas/tratamiento farmacológico , Arritmias Cardíacas/etiología , Compuestos Bicíclicos Heterocíclicos con Puentes/efectos adversos , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Sinergismo Farmacológico , Humanos , Hiperfosfatemia/etiología , Hiperfosfatemia/terapia , Hiperuricemia/tratamiento farmacológico , Hiperuricemia/etiología , Leucemia Linfocítica Crónica de Células B/enzimología , Diálisis Renal , Factores de Riesgo , Índice de Severidad de la Enfermedad , Sulfonamidas/efectos adversos , Sulfonamidas/uso terapéutico , Síndrome de Lisis Tumoral/diagnóstico , Síndrome de Lisis Tumoral/tratamiento farmacológico , Síndrome de Lisis Tumoral/prevención & control , Urato Oxidasa/uso terapéutico
7.
BMJ ; 368: m165, 2020 01 20.
Artículo en Inglés | MEDLINE | ID: mdl-31959618
8.
Chem Commun (Camb) ; 56(7): 1093-1096, 2020 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-31894764

RESUMEN

We prepared novel conjugated polymer based NIR-II nanoparticles, which display extremely high photothermal conversion efficiency (65%). Both in vitro and in vivo investigations revealed that the as-prepared nanoparticles exhibit excellent theranostic properties including an extremely high cancer cell killing ability, admirable tumor elimination efficiency (100%) and a remarkable photoacoustic imaging contrast enhancing ability.


Asunto(s)
Antineoplásicos/uso terapéutico , Nanopartículas/uso terapéutico , Compuestos de Organosilicio/uso terapéutico , Polímeros/uso terapéutico , Tiadiazoles/uso terapéutico , Animales , Antineoplásicos/química , Antineoplásicos/efectos de la radiación , Células Hep G2 , Humanos , Hipertermia Inducida/métodos , Rayos Infrarrojos , Ratones , Microscopía Confocal/métodos , Microscopía Fluorescente/métodos , Nanopartículas/química , Nanopartículas/efectos de la radiación , Compuestos de Organosilicio/química , Compuestos de Organosilicio/efectos de la radiación , Técnicas Fotoacústicas/métodos , Polímeros/química , Polímeros/efectos de la radiación , Nanomedicina Teranóstica/métodos , Tiadiazoles/química , Tiadiazoles/efectos de la radiación
9.
J Biomed Nanotechnol ; 16(1): 1-13, 2020 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-31996281

RESUMEN

Targeted drug delivery systems have currently demonstrated considerable potential clinical benefits in cancer treatment. Curcumin has become a candidate anti-tumor drug for the therapy of glioblastoma multiforme (GBM) by increasing cell apoptosis and suppressing cell proliferation. In current research, we explored a novel targeted drug delivery system with a self-assembly measure by curcumin, MPEG-PLA and Fa-PEG-PLA. Compared with free curcumin and Cur/MPEG-PLA, Cur/Fa-PEG-PLA can remarkably suppress the growth of GL261 cells and promote apoptotic rate. Moreover, after the procession of tumor-bearing mice with curcumin/Fa-PEG-PLA complex, tumor growth in subcutaneous and intracranial tumor models were repressed via suppressing angiogenesis and facilitating apoptosis in vivo. The Curcumin/Fa-PEG-PLA nanoparticle may be a novel drug for the therapy of GBM.


Asunto(s)
Curcumina , Glioma , Animales , Antineoplásicos , Línea Celular Tumoral , Portadores de Fármacos , Ácido Fólico , Ratones , Micelas , Polietilenglicoles
10.
J Biomed Nanotechnol ; 16(1): 40-53, 2020 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-31996284

RESUMEN

In recent decades, a large number of research studies have been conducted to improve the treatment strategy against epithelial ovarian cancer, but women in advanced stage still have poor outcomes. The development of advanced treatments must be continued to overcome the limitation. Docetaxel, a semi-synthetic product derived from the Pacific Taxus extract, has been studied for many years for its potent anticancer applications. Aiming to solve the problems of its highly lipophilicity, insolubility and adverse side effects, nanocarriers were applied. Relying on the integration of nanoparticles which had optimized sizes, shapes, and surface properties, the effect of docetaxel was enhanced. In this study, we designed a novel drug loaded gel-forming nanoparticle system (Doc-NMs-hydrogel composites), which acted as a sustained drug depot for docetaxel. Docetaxel was encapsulated into MPEG-PCL and then into blank thermosensitive hydrogel Pluronic F-127. Characterization showed that the prepared Doc-NMs had high drug loading (7%), minor particle size (37 nm), relatively good water solubility. Moreover, the cytotoxicity, apoptosis induction and the antitumor effects of Doc-NMs-hydrogel composites on mice abdominal SKOV-3 ovarian cancer model were investigated in vivo. Compared with other groups, at the same dosage, Doc-NMs-hydrogel composites show better apoptosis induction and cell growth inhibition. In conclusion, the prepared Doc-NMs-hydrogel composites enhanced anti-tumor activity by increasing local docetaxel concentration, maintaining stable and sustained drug release, prolonging drug retention time in tumors, and reducing toxicity to normal tissues. Doc-NMs-hydrogel composites might have great potential clinical application in anti-ovarian cancer activity.


Asunto(s)
Neoplasias Ováricas , Animales , Antineoplásicos , Línea Celular Tumoral , Docetaxel , Portadores de Fármacos , Sistemas de Liberación de Medicamentos , Femenino , Humanos , Hidrogeles , Ratones , Micelas , Nanopartículas , Taxoides
12.
Eur J Med Chem ; 188: 112021, 2020 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-31901743

RESUMEN

A series of novel sulfonamide derivatives bearing pyrrole and pyrrolopyrimidine scaffolds were synthesized and screened as carbonic anhydrase inhibitors. The inhibition activity of the synthesized compounds was evaluated against the cytosolic human carbonic anhydrase isoforms I and II and the transmembranal isoforms IX and XII. Several candidates showed potent inhibitory activity against IX and XII isoforms. Furthermore, ex vivo screening of cytotoxic selectivity and activity of the most potent derivatives were carried out against normal cells (WI38) and cervical cancer cell line (HeLa) under normal and hypoxic conditions using acetazolamide as reference drug. Compound 11b potency was nearly three folds higher in hypoxic than normoxic condition whereas that of compound 11f was nearly four folds higher in hypoxic vs. normoxic HeLa cells. All the screened derivatives exhibited less potency on normal cells (WI38). Molecular docking was carried out to discover the possible binding mode of compounds within the active site of isoform CA IX.


Asunto(s)
Antineoplásicos/farmacología , Inhibidores de Anhidrasa Carbónica/farmacología , Pirimidinas/farmacología , Pirroles/farmacología , Sulfonamidas/farmacología , Antígenos de Neoplasias/química , Antígenos de Neoplasias/metabolismo , Antineoplásicos/síntesis química , Antineoplásicos/toxicidad , Anhidrasa Carbónica IX/química , Anhidrasa Carbónica IX/metabolismo , Inhibidores de Anhidrasa Carbónica/síntesis química , Inhibidores de Anhidrasa Carbónica/toxicidad , Dominio Catalítico , Ensayos de Selección de Medicamentos Antitumorales , Células HeLa , Humanos , Simulación del Acoplamiento Molecular , Pirimidinas/síntesis química , Pirimidinas/toxicidad , Pirroles/síntesis química , Pirroles/toxicidad , Sulfonamidas/síntesis química , Sulfonamidas/toxicidad
13.
Eur J Med Chem ; 188: 111988, 2020 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-31901746

RESUMEN

In connection with our continued research to generate new aza-fused heteroaromatic chemical scaffolds, we developed a highly atom-economical three-component route to novel 3,4-dihydropyrrolo[1,2-a]pyrazine ring skeleton multi-functionalized on the pyrazine unit. This [4+1+1] annulation approach led us to gain access to a new N-fused bicyclic chemical space having two distinctive functional groups (heteroaryl and aroyl) in a trans manner. Investigation of anticancer activity of the synthesized compounds and their derivatives revealed that (3R*,4S*)-3-(4-bromophenyl)-4-(4-fluorobenzoyl)-2-(2-oxo-2-phenylethyl)-3,4-dihydropyrrolo[1,2-a]pyrazin-2-ium bromide (3h) has potent anticancer activity. 3h significantly inhibited cell viability in prostate cancer cells (PC-3) and breast cancer cells (MCF-7) with IC50 value of 1.18 ± 0.05 µM and 1.95 ± 0.04 µM, respectively. In addition, 3h strongly reduced cell migration in a dose dependent manner, and induced apoptosis via caspase-3 activation and cleavage of PARP in PC-3 and MCF-7 cells. Our results in this study imply that 3h can be a potential anticancer agent against prostate cancer and breast cancer.


Asunto(s)
Antineoplásicos/farmacología , Pirazinas/farmacología , Pirroles/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Caspasa 3/metabolismo , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Estructura Molecular , Poli(ADP-Ribosa) Polimerasas/metabolismo , Pirazinas/síntesis química , Pirazinas/química , Pirroles/síntesis química , Pirroles/química
14.
Crit Rev Oncol Hematol ; 145: 102822, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31911396

RESUMEN

Cardiovascular diseases (CVD) and cancer are still the leading causes of death. There are many common etiologic factors, especially smoking and obesity. Therefore, it is not uncommon for CVD and cancer to coexist. Drug-drug interactions (DDIs) inevitably occur in this group of patients, where polypharmacy is increasing due to older age and multiple comorbidities. However, multidisciplinary studies, especially close collaboration of medical oncologists and cardiologists, who deals with the diagnosis and treatment of these diseases, awareness and preventive approaches to DDIs may reduce serious morbidity and mortality. In this review, information about the common treatments used in cardiology and oncology and possible DDIs are discussed.


Asunto(s)
Antineoplásicos , Fármacos Cardiovasculares , Enfermedades Cardiovasculares , Interacciones de Drogas , Neoplasias , Anciano , Antineoplásicos/efectos adversos , Antineoplásicos/farmacología , Cardiología , Fármacos Cardiovasculares/efectos adversos , Fármacos Cardiovasculares/farmacología , Enfermedades Cardiovasculares/tratamiento farmacológico , Humanos , Neoplasias/tratamiento farmacológico
15.
Chem Soc Rev ; 49(2): 593-641, 2020 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-31915764

RESUMEN

Glycoconjugates and their applications as lectin ligands in biology have been thoroughly investigated in the past decades. Meanwhile, the intrinsic properties of such multivalent molecules were limited essentially to their ability to bind to their receptors with high selectivity and/or avidity. The present review will focus on multivalent glycoconjugates displaying an additional capability such as fluorescence properties not only for applications toward imaging of cancer cells and detection of proteins or pathogens but also for drug delivery systems toward targeted cancer therapy. This review is a collection of research articles discussed in the context of the structural features of fluorescent glycoconjugates organized according to their fluorescent core scaffold and with their representative applications.


Asunto(s)
Colorantes Fluorescentes/química , Glicoconjugados/química , Antineoplásicos/administración & dosificación , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Sistemas de Liberación de Medicamentos , Fluorescencia , Humanos , Neoplasias/tratamiento farmacológico
16.
Adv Clin Chem ; 94: 219-259, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31952572

RESUMEN

Chemotherapy is the most common clinical choice of treatment for cancer, however, acquired chemoresistance is a major challenge that limits the successful outcome of this option. Systematic review of in vitro, in vivo, preclinical and clinical studies suggests that acquired chemoresistance is polygenic, progressive, and involve both genetic and epigenetic heterogeneities and perturbations. Various mechanisms that confer resistance to chemotherapy are tightly controlled by epigenetic regulations. Poised epigenetic plasticity and temporal increase in epigenetic alterations upon chemotherapy make chemoresistance likely an epigenetic-driven process. The transient and reversible nature of epigenetic modulations enable ways to intervene the epigenetic re-programing associated with acquired chemoresistance via application of epigenetic modifying drugs. This review discusses recent understandings behind the various mechanisms of acquired chemoresistance that are under the control of epigenetic drivers, potential application of epigenetic-based drugs in resensitizing refractory cancers to chemotherapy, the limitations and future scope for clinical application of epigenetic therapeutics in successfully addressing chemoresistance.


Asunto(s)
Antineoplásicos/farmacología , Resistencia a Antineoplásicos , Epigénesis Genética/efectos de los fármacos , Metilación de ADN , Humanos , Neoplasias/genética
18.
Chem Commun (Camb) ; 56(8): 1271-1274, 2020 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-31903456

RESUMEN

A dual-cavity basket 16-, holding six γ-aminobutyric acids at its termini, encapsulates variously sized aromatics 2-7+, including four anthracyclines (8+-11+), driven by the hydrophobic effect and hydrogen bonding (HB). In particular, the formation of stable (K = 1012 M-2) anthracycline complexes [(8+-11+)2⊂16-], assembled into nanoparticles, occurred with positive homotropic cooperativity (α = 4K2/K1 = 1.1 ± 0.3 × 102-1.3 ± 0.7 × 103) in PBS medium. Importantly, weakening the first binding event (K1, i.e. by removing HBs) turned the second one (K2) more favorable. The finding is of interest for developing cooperative nano-antidotes acting as biodetoxifying agents.


Asunto(s)
Antraciclinas/farmacología , Antídotos/farmacología , Antineoplásicos/farmacología , Nanoestructuras/química , Regulación Alostérica/efectos de los fármacos , Antraciclinas/síntesis química , Antraciclinas/química , Antídotos/síntesis química , Antídotos/química , Antineoplásicos/química , Enlaces de Hidrógeno , Interacciones Hidrofóbicas e Hidrofílicas , Modelos Moleculares , Estructura Molecular
19.
Life Sci ; 244: 117332, 2020 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-31962133

RESUMEN

AIMS: It has been demonstrated that reduced expression of alpha7 nicotinic acetylcholine receptor (α7nAChR) led to reduced chemotherapeutic drugs resistance in various cancer cells. However, whether small interfering RNA (siRNA) mediated knockdown of α7nAChR can reduce sorafenib (SOR) resistance in HCC cells remains to be determined. MATERIALS AND METHODS: The effects of α7nAChR-siRNA in combination with SOR treatment was analyzed in human (HepG2) and mouse (Hepa 1-6) HCC cell lines. The MTT, DAPI staining and flow cytometry assays were applied to measure the cell viability, apoptosis and cell cycle progression of the cells. Also, the changes in the mRNA and protein levels of the α7nAChR were measured by quantitative real-time PCR and western blot analysis, respectively. KEY FINDINGS: The results revealed that SOR increased both mRNA and protein levels of α7nAChR in HCC cells. Treatment with α7nAChR-siRNA abolished these effects. Also, SOR treatment in combination with α7nAChR-siRNA significantly sensitizes HCC cells to SOR cytotoxicity. This combination therapy significantly induced HCC cells apoptosis compared to SOR alone. SIGNIFICANCE: These experimental results indicate that knockdown of α7nAChR by siRNA increased the SOR antitumor activity of HCC cells and suggests that this additive combination is a promising drug candidate for HCC therapy.


Asunto(s)
Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Sorafenib/farmacología , Receptor Nicotínico de Acetilcolina alfa 7/genética , Animales , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Resistencia a Antineoplásicos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Ratones , ARN Interferente Pequeño/administración & dosificación , ARN Interferente Pequeño/genética , Receptor Nicotínico de Acetilcolina alfa 7/metabolismo
20.
Anticancer Res ; 40(1): 53-66, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31892552

RESUMEN

BACKGROUND/AIM: Medulloblastoma (MB) accounts for ~20% of pediatric malignant central nervous system tumors. Treatment strategies, including surgery, radiation therapy and/or chemotherapy, are effective, but recurrence and metastasis frequently occur. Therefore, novel therapies are required. Herein, the effects of fibroblast growth factor receptor (FGFR) and phosphoinositide 3-kinase (PI3K) inhibitors on MB cells lines were evaluated. MATERIALS AND METHODS: MB cell lines (UW228-3, DAOY, Med8a, D425, D283) were tested for sensitivity to FGFR (AZD4547) and PI3K (BEZ235 and BYL719) inhibitors by viability, cytotoxicity, apoptosis, and proliferation assays. RESULTS: Single treatments with FGFR and PI3K inhibitors decreased viability and proliferation in a dose-dependent pattern in most cell lines. Combinination of the two type of drugs, increased sensitivity, especially of the most resistant cell line UW228-3. CONCLUSION: Combination treatments with FGFR and PI3K inhibitors were superior to single treatments with FGFR and PI3K inhibitors, especially with BEZ235, for MB cell lines.


Asunto(s)
Meduloblastoma/metabolismo , Fosfatidilinositol 3-Quinasa/metabolismo , Receptores de Factores de Crecimiento de Fibroblastos/metabolismo , Transducción de Señal/efectos de los fármacos , Animales , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Caspasa 3/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Humanos , Meduloblastoma/patología , Inhibidores de Proteínas Quinasas/farmacología , Ensayos Antitumor por Modelo de Xenoinjerto
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