RESUMO
To observe the cytotoxic effect of the photodynamic therapy mediated by the traditional photosensitizer polyhematoporphyrin (C(34)H(38)N(4)NaO(5), Photosan-II Photosan-II was loaded into HSNP by one-step wet chemical, PS) and hollow silica nanoparticles (HSNP) loaded PS on Huh-7 cells and compare the cytotoxic effects. -based synthetic route. The cellular viability was determined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Apoptotic and necrotic cells were measured by flow cytometry. The suitable drug concentrations of free PS and HSNP loaded PS on Huh-7 cells were 20mg/L and 5mg/L respectively, and the suitable incubation time were 4 h and 2 h respectively. Under the same drug concentration, the survival rates of free PS and HSNP loaded PS were 62.46%±1.93% and 6.54%±1.24% <. Under the same drug concentration and incubation time, the total rates of apoptosis necrosis caused by free PS and HSNP loaded PS mediated PDT were respectively 22.00% ± 2.24% and 87.23% ± 2.1% <. PS-loaded HSNP mediated PDT can inhibit proliferation of cancer cells and induce apoptosis more quickly and effectively. As the loading system of PS, HSNP can make the photosensitizer have stronger solubility and drug concentration efficiency, which can significantly improve the therapeutic effect of PDT.
Assuntos
Nanopartículas Metálicas/administração & dosagem , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/farmacologia , Dióxido de Silício/administração & dosagem , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Fármacos Fotossensibilizantes/administração & dosagem , Porfirinas/administração & dosagemRESUMO
Worldwide use of robotic-assisted hepatectomy has increased dramatically over the past two decades. The role of robotic liver surgery is still controversial, especially with respect to its long-term oncological outcomes in treating early-stage hepatocellular carcinoma (HCC). The Glissonean approach is a fundamental technique for anatomical resection using open and laparoscopic liver surgery. To our knowledge, there have been few reports on purely robotic anatomical segmentectomy 7 for HCC using the Glissonean approach have been described. The present study describes the technical details and surgical outcomes of totally robotic segmentectomy 7 using the Glissonean approach. Fourteen patients with HCC limited to segment 7 underwent segmentectomy 7 from January 2019 through April 2023 in our hospital. The surgical techniques, peri-operative, and oncological outcomes were analyzed. Purely robotic anatomical segmentectomy 7 using the Glissonean approach was safe and feasible with the technology described herein in all of the 14 patients. The peri-operative and oncological outcomes were better and/or comparable with those of other similar hepatic resections using open approach and/or laparoscopic approach. The median follow-up time was 18 months. Intrahepatic recurrence occurred in 2 (14.3%) patient within one year following surgery. The 3-year overall survival rate was 81%. Although technically challenging, the purely robotic segmentectomy 7 could be performed safely and simultaneously with oncological radicality using the Glissonean approach.
Assuntos
Carcinoma Hepatocelular , Hepatectomia , Neoplasias Hepáticas , Procedimentos Cirúrgicos Robóticos , Humanos , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/patologia , Procedimentos Cirúrgicos Robóticos/métodos , Hepatectomia/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Resultado do Tratamento , Taxa de Sobrevida , Adulto , Laparoscopia/métodos , Seguimentos , Recidiva Local de NeoplasiaRESUMO
Triptolide (TPL) is a diterpenoid triepoxide with broad antitumor efficacy, while lack of mechanism of action, severe systemic toxicity, and poor water solubility of TPL limited its usage. To unveil the mechanism of action and improve the pharmaceutical properties of TPL, here we explored the molecular mechanism of TPL and then fabricated TPL-loaded membrane protein-chimeric liposomes (TPL@MP-LP) and tested its anticancer efficacy against hepatocellular carcinoma (HCC). CCK8 assay, colony formation assay, EdU assay, and flow cytometry were used to examine the activity of TPL. RNA sequence and gain-and-loss of function assays were used to explore the molecular mechanisms. TPL@MP-LP was characterized by size, zeta potential, polydispersity index, and transmission electron microscopy. Cellular uptake and cell viability assay were performed to evaluate the internalization and anticancer efficacy of TPL@MP-LP in vitro. Biodistribution and in vivo antitumor efficacy of TPL@MP-LP were evaluated on orthotopic HCC mice models. TPL robustly inhibited HCC cells by inducing cell proliferation arrest, apoptosis via the mitochondrial pathway, and necroptosis via RIPK1/RIPK3/MLKL signaling. TPL was successfully loaded into MP-LP, with a drug-loading capacity of 5.62 ± 0.80%. MP-LP facilitated TPL internalization and TPL@MP-LP exerted enhanced anticancer efficacy against Huh7 cells. TPL@MP-LP showed targeting ability to the tumor site. More importantly, TPL@MP-LP treatment suppressed tumor growth but showed minimal damage to liver and renal functions. TPL exerted anticancer effects on HCC via inducing cell proliferation arrest, apoptosis, and necroptosis, and the MP-LP might be a promising delivery strategy to improve the antitumor efficacy while mitigating toxicity of TPL for HCC therapy.
Assuntos
Carcinoma Hepatocelular/patologia , Diterpenos/farmacologia , Lipossomos/química , Neoplasias Hepáticas/patologia , Proteínas de Membrana/química , Fenantrenos/farmacologia , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Química Farmacêutica , Diterpenos/administração & dosagem , Portadores de Fármacos , Compostos de Epóxi/administração & dosagem , Compostos de Epóxi/farmacologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Tamanho da Partícula , Fenantrenos/administração & dosagem , Distribuição Aleatória , Transdução de Sinais/efeitos dos fármacos , Propriedades de SuperfícieRESUMO
Long noncoding RNA serves important roles in gastric cancer (GC). However, the prognostic significance and tumorigenesis effect of AFAP1-antisense RNA 1 (AS1) in GC remain to be clarified. The present study was conducted in order to determine the expression level of AFAP1-AS1 by reverse transcription-quantitative polymerase chain reaction. It was demonstrated that AFAP1-AS1 expression level was higher in GC tissues in comparison with adjacent tissues. By analyzing 66 GC tissue specimens, AFAP1-AS1 expression level was found to be markedly associated with tumor size, clinical stage and differentiation. By performing multivariate Cox regression test, AFAP1-AS1 expression level was confirmed to be an independent factor for poor prognosis in patients with GC. Furthermore, SGC-7901 and BGC-823 cells were used for further investigation following transfection of an AFAP1-AS1 short hairpin RNA lentiviral vector. Knockdown of AFAP1-AS1 significantly inhibited GC cell proliferation, migration and invasion abilities in vitro. Finally, nude mice experiments confirmed that downregulation of AFAP1-AS1 in GC cells suppressed tumor growth in vivo. In conclusion, the results of the present study suggested that AFAP1-AS1 may serve as a valuable prognostic indicator and therapeutic target for GC.
RESUMO
Ornithine decarboxylase (ODC) plays a critical role in cell proliferation and is overexpressed in a variety of cancers. Furthermore, γ-aminobutyric acid (GABA) content and glutamate decarboxylase (GAD) activity are increased in neoplastic tissues in colon and breast cancer. However, few studies have examined these molecules in gallbladder cancer specimens. We observed the expression levels of ODC and GAD65 in benign and malignant lesions of the gallbladder and investigated their clinicopathological significance for the first time. The expression levels of ODC and GAD65 in specimens from gallbladder adenocarcinoma (n=108), peritumoral tissues (n=46), adenomatous polyps (n=15) and chronic cholecystitis (n=35) were detected using immunohistochemical methods. Kaplan-Meier survival and Cox regression analyses were carried out to explore the clinical and pathological correlations. The levels of positive staining of ODC and GAD65 were significantly higher in gallbladder adenocarcinoma than in peritumoral tissues, adenomatous polyps and chronic cholecystitis. The KaplanMeier survival analysis and Cox regression analysis showed that the expression of ODC and GAD65 correlated significantly with the one-year survival rate and the mean survival time of the patients postoperatively. We conclude that the overexpression of ODC and GAD65 are significant in the carcinogenesis and progression of gallbladder adenocarcinoma. They may be important biological markers for the evaluation of biological behaviors and the prognosis of gallbladder adenocarcinoma.