RESUMEN
Prostate cancer is one of the predominant cancers affecting men and has been widely reported. In the past, various therapies and drugs have been proposed to treat prostate cancer. Among these treatments, gene therapy has been considered to be an optimal and widely applicable treatment. Furthermore, due to the increased specificity of gene sequence complementation, the targeted delivery of complementary gene sequences may represent a useful treatment in certain instances. Various gene therapies, including tumor-suppressor gene therapy, suicide gene therapy, immunomodulation gene therapy and anti-oncogene therapies, have been established to treat a wide range of diseases, such as cardiac disease, cystic fibrosis, HIV/AIDS, diabetes, hemophilia, and cancers. To this end, several gene therapy clinical trials at various phases are underway. This overview describes the developments and progress in gene therapy, with a special focus being placed on prostate cancer.
Asunto(s)
Terapia Genética , Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/terapiaRESUMEN
In the present study, 1-(3,5-dimethylphenyl)-6-methyl-1H-pyrazolo[4,3-c]pyridin-4 (5H)-one (DPMPP) was investigated as an antiproliferative agent for prostate cancer cells and the mechanism of its action was studied. Cell lines 22Rv1 and SGC7901 were used as in vitro models of prostate cancer. The DPMPP treatment inhibited proliferation of 22Rv1 and SGC7901 cells in dose-depended manner. The viability of 22Rv1 and SGC7901 cells was reduced to 21 and 19%, respectively after treatment with 32 µM DPMPP. In DPMPP treated (16 µM) 22Rv1 and SGC7901 cells apoptosis increased to 62.78 and 68.51%, respectively. Moreover, DPMPP treatment caused cell cycle arrest in S phase and inhibition of PI3K/AKT activation. In the same time ROS production showed elevation and MMP (Matrix MetalloProteinase) decreased in the cells. Apparently DPMPP induces cytotoxicity through induction of oxidative response and apoptosis in prostate cancer cells in vitro. The PI3K/Akt/ERK phosphorylation was inhibited, while p21 and p53, death receptor, expression was promoted by DPMPP treatment. Therefore, DPMPP has a potential to be used as a therapeutic agent for treatment of prostate cancer.
Asunto(s)
Antineoplásicos/farmacología , Fosfatidilinositol 3-Quinasa Clase I/antagonistas & inhibidores , Janus Quinasa 2/antagonistas & inhibidores , Neoplasias de la Próstata/tratamiento farmacológico , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Piridonas/farmacología , Factor de Transcripción STAT3/antagonistas & inhibidores , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Regulación hacia Abajo , Humanos , Masculino , Fosforilación/efectos de los fármacos , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/psicología , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
BACKGROUND AIMS: Minimal change nephrotic syndrome is the most frequent cause of nephrotic syndrome in childhood. Current treatment regimes, which include glucocorticoid hormones and immunosuppressive therapy, are effective and have fast response. However, because of the side effects, long treatment course, poor patient compliance and relapse, novel approaches for the disease are highly desired. METHODS: The adriamycin-induced nephrotic rat model was established. Rats were allocated to a model group, a prednisone group or mesenchymal stromal cell (MSC) group. Clinical parameters in each treatment group were determined at 2 weeks, 4 weeks and 8 weeks. The messenger RNA (mRNA) levels of synaptopodin, p21 and monocyte chemoattractant protein-1 were determined through the use of quantitative real-time-polymerase chain reaction. Protein levels were determined by means of Western blot or enzyme-linked immunosorbent assay. Podocytes were isolated and apoptotic rate after adriamycin with or without MSC treatment was analyzed by means of flow cytometry. RESULTS: MSC intervention improved renal function as assessed by urinary protein, blood creatinine and triglyceride levels. MSC intervention reduced adriamycin-induced renal tissue damage visualized by immunohistochemistry and light and electron microscopic analysis and reduced adriamycin-induced podocyte apoptosis. After MSC intervention, mRNA and protein levels of synaptopodin and p21 in renal cortex were significantly increased. MSCs also restored synaptopodin mRNA and protein expression in isolated podocytes. In addition, monocyte chemoattractant protein-1 mRNA in renal cortex and protein level in serum of the MSC treatment group were significantly decreased compared with that in the adriamycin-induced nephropathy model group. CONCLUSIONS: Our data indicate that MSCs could protect rats from adriamycin-induced minimal change nephrotic syndrome, and the protective effects of MSCs are mediated through multiple actions.
Asunto(s)
Riñón/efectos de los fármacos , Trasplante de Células Madre Mesenquimatosas , Nefrosis Lipoidea/patología , Nefrosis Lipoidea/terapia , Animales , Quimiocina CCL2/biosíntesis , Doxorrubicina/toxicidad , Regulación de la Expresión Génica , Humanos , Riñón/patología , Células Madre Mesenquimatosas/citología , Proteínas de Microfilamentos/biosíntesis , Nefrosis Lipoidea/inducido químicamente , Prednisona/administración & dosificación , ARN Mensajero/biosíntesis , Ratas , Proteínas de Unión al GTP rho/biosíntesisRESUMEN
OBJECTIVE: Bladder cancer (BC) is the most common malignant tumour of the urinary system, and radical cystectomy combined with pelvic lymph node dissection (LND) is the standard treatment for BC. We conducted this meta-analysis to explore the efficacy and safety of extended lymph node dissection in radical cystectomy for BC. METHODS: PubMed, Embase, ProQuest PsycINFO, CINAHL, Web of Science and The Cochrane Library databases were searched for studies on extended lymph node dissection during radical BC surgery. The search time limit was from the establishment of the database to December 2023. Screening and quality assessment of literature were conducted. This meta-analysis was conducted to evaluate the influence of different lymph node dissection methods on recurrence-free survival (RFS), overall survival (OS), operation time, 90-day readmission rate and postoperative complication rate. RESULTS: A total of 15 studies were included, including 4854 patients. All studies were of high quality. This meta-analysis showed no statistically significant difference in the operation time, postoperative complications and 90-day hospitalisation rate between the two groups of patients. The harvested volume of lymph nodes, RFS and OS rate were not statistically different. CONCLUSIONS: Among patients with BC undergoing radical cystectomy, extended lymph node dissection did not have a significant effect on operative time, 90-day readmission rates or postoperative complication rates. Thus, extended lymph node dissection is a safe treatment that does not increase the patient's surgical risk.
Asunto(s)
Cistectomía , Escisión del Ganglio Linfático , Neoplasias de la Vejiga Urinaria , Humanos , Escisión del Ganglio Linfático/métodos , Neoplasias de la Vejiga Urinaria/cirugía , Neoplasias de la Vejiga Urinaria/patología , Cistectomía/métodos , Resultado del Tratamiento , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiologíaRESUMEN
A composite lithium electrolyte composed of polyelectrolyte-grafted nanoparticles and polyethylene glycol dimethyl ether (PEGDME) is synthesized and characterized. Polyanions immobilized by the silica nanoparticles have reduced anion mobility. Composite nanoparticles grafted by poly(lithium 4-styrenesulfonate) only have moderate conductivity at 60 °C. Almost an order increase of the conductivity to â¼10(-6) S/cm is achieved by co-polymerization of the poly(ethylene oxide) methacrylate with sodium 4-styrenesulfonate, which enhances dissociation between lithium cation and polyanion and facilitates lithium ion transfer from the inner part of the polyelectrolyte layer. This composite electrolyte has the potential to suppress lithium dendrite growth and enable the use of lithium metal anode in rechargeable batteries.
RESUMEN
Lithium bis(trifluoromethane) sulfonamide (TFSI) is a promising electrolyte salt in lithium batteries, due to its good conductivity and high dissociation between the lithium cation and its anion. By tethering N-pentane trifluoromethane sulfonamide (C5NHTf), a TFSI analogue molecule, onto the surface of silica nanoparticle as a monolayer coverage should increase the Li(+) transference number to unity since anions bound to particles have reduced mobilities. Silica polymer composite has better mechanical property than that of the pure PEO. Analogously trifluoromethane sulfonic aminoethyl methacrylate (TfMA), a TFSI analogue vinyl monomer, was polymerized on silica nanoparticle surface as a multilayer coverage. Anchored polyelectrolytes to particle surfaces offer multiple sites for anions, and in principle the carrier concentration would increase arbitrarily and approach the carrier concentration of the bulk polyelectrolyte. Monolayer grafted nanoparticles have a lithium content of 1.2 × 10(-3) g Li/g, and multilayer grafted nanoparticles have a lithium content over an order higher at 2 × 10(-2) g Li/g. Electrolytes made from monolayer grafted particles exhibit a weak conductivity dependence on temperature, exhibiting an ionic conductivity in the range of 10(-6) S/cm when temperatures increase to 80 °C. While electrolytes made from multilayer grafted particles show a steep increase in conductivity with temperature with an ionic conductivity increase to 3 × 10(-5) S/cm at 80 °C, with an O/Li ratio of 32.
RESUMEN
Hole-conducting silica/polymer nanocomposites exhibit interesting physical and chemical properties with important applications in the field of energy storage and hybrid solar cells. Although the conventional strategy of grafting hole-conducting polymer onto the surface of silica nanoparticles is to use in situ oxidative polymerization, a promising alternative of using surface-initiated controlled living radical polymerization has arisen to anchor the polymer on the silica. The resulting silica/polymer nanocomposites from the latter method are more chemically and thermally stable because of the strong covalent bonding compared to the electrostatic interaction from in situ polymerization. The use of these nanocomposites mixed with spiro-MeOTAD (2,2',7,7'-tetrakis(N,N-di-p-methoxyphenylamine)-9,9'-spirobifluorene) as a new hole conductor in the application of solid-state dye-sensitized solar cell (ss-DSSC) is reported here. The power conversion efficiency of this ss-DSSC is higher than the full spiro-MeOTAD ss-DSSC. Notably, the short circuit current improves by 26%. It is explained by large size silica/polymer nanocomposites forming an additional light scattering layer on the top of photoanode. This is the first time a conductive light scattering layer is introduced into ss-DSSC to enhance cell performance.