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BACKGROUND AND PURPOSE: The use of oncolytic viruses as a gene therapy vector is an area of active biomedical research, particularly in the context of cancer treatment. However, the actual therapeutic success of this approach to tumor elimination remains limited. As such, the present study was developed with the goal of simultaneously enhancing the antitumor efficacy of oncolytic viruses and the local immune response by combining the Ad-GD55 oncolytic adenovirus and an antibody specific for the TIM-3 immune checkpoint molecule (α-TIM-3). APPROACH AND KEY RESULTS: The results of Virus and cell-mediated cytotoxicity assay, qPCR, and Western immunoblotting showed that Ad-GD55-α-Tim-3 oncolytic adenovirus is capable of inducing α-TIM-3 expression within hepatoma cells upon infection, and Ad-GD55-α-TIM-3 exhibited inhibitory efficacy superior to that of Ad-GD55 when used to treat these tumor cells together with the induction of enhanced intracellular immunity. In vivo experiments revealed that Ad-GD55-α-TIM-3 administration was sufficient to inhibit tumor growth and engage in a more robust local immune response within the simulated tumor immune microenvironment. CONCLUSION AND IMPLICATIONS: These results highlighted the promising therapeutic effects of Ad-GD55-α-TIM-3 oncolytic adenovirus against HCC in vitro and in vivo. As such, this Ad-GD55-α-TIM-3 oncolytic adenovirus may represent a viable approach to the treatment of hepatocellular carcinoma.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Viroterapia Oncolítica , Virus Oncolíticos , Humanos , Neoplasias Hepáticas/metabolismo , Carcinoma Hepatocelular/metabolismo , Adenoviridae/genética , Viroterapia Oncolítica/métodos , Receptor 2 Celular del Virus de la Hepatitis A/metabolismo , Línea Celular Tumoral , Ensayos Antitumor por Modelo de Xenoinjerto , Virus Oncolíticos/genética , Anticuerpos , Inmunidad , Microambiente TumoralRESUMEN
Interleukin-7 (IL-7) is a cytokine belonging to the chemokine family. It plays a key role in the differentiation, development, and maturation of T lymphocytes and B lymphocytes, which is pivotal to adaptive immunity. In addition to its role in lymphocyte development, recent studies have indicated the antitumor functions of IL-7 in the tumor microenvironment. In this review, we discuss the role of IL-7 in tumors and summarize its antitumor potential and clinical application in lymphoma, leukemia, breast cancer, colon cancer, and so on. Furthermore, the combinational strategies of IL-7 and other antitumor drugs have been also discussed.
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Neoplasias del Colon , Interleucina-7 , Quimiocinas , Citocinas , Humanos , Microambiente TumoralRESUMEN
OBJECTIVE:To provide reference for clinical rational drug use in advanced breast cancer patients with grade Ⅳmyelosupression induced by chemotherapy. METHODS:108 advanced breast cancer patients with grade Ⅳ myelosupression in-duced by chemotherapy in our hospital from July 2014 to June 2015 were retrospectively analyzed on the characteristics of myelosu-pression and the reasonability of chemotherapy reguneb and adjuvant drug for myelosupression. RESULTS:The incidence of gradeⅣ myelosupression induced by chemotherapy in advanced breast cancer patients was 8.3%,chiefly manifesting as grade Ⅳ neutro-penia(94.4%). The chemotherapy regimens which induced grade Ⅳ myelosupression were mainly docetaxel+epirubicin,docetaxel, vinorelbine+lobaplatin;irrational chemotherapy plan mainly shows irrational pretreatment of chemotherapy drug (32 cases, 91.4%);irrational therapy of myelosupression mainly manifested as rophylactic use of antimicrobials without indication,unsuitable choice of antibiotics(29 cases for each,36.2% for each). CONCLUSIONS:The use of drugs used in advanced breast cancer pa-tients with grade Ⅳ myelosupression induced by chemotherapy is basically rational,yet it is far from perfect in pretreatment of che-motherapy drug and therapy for gradeⅣmyelosupression,which should be further improved.
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<p><b>OBJECTIVE</b>The three-dimensional (3D) structure of left atrial appendage (LAA) in atrial fibrillation patients were reconstructed by Mimics 3D imaging system, aiming at guiding for selection of both the size and location of the closure devices and making preliminary risk assessment of LAA closure with Watchman system.</p><p><b>METHODS</b>Inclusion criteria were: ten voluntary patients with both atrial fibrillation and indication for LAA closure aging from 40 to 85 years old with contraindication for oral anticoagulants or unwillingness to take long-term oral anticoagulation therapy from May to December 2014. 3D reconstruction of LAA was preoperatively made by Mimics 3D imaging system. With the Mimics 3D reconstruction model and the results of both transesophageal echocardiography (TEE) and LAA radiography, the size and location for the closure device were chosen. The devices were planted at the ostium of the LAA.</p><p><b>RESULTS</b>Ten atrial fibrillation patients were enrolled (average age: (66.3±11.9) years old) and all successfully implanted with the Watchman LAA closure devices. Nine of them were with non-valvular atrial fibrillation with average CHADS2-VAS score (3.2±1.7) and HAS-BLED score (2.7±1.6). The rest one was a valvular atrial fibrillation patient with the history of the percutaneous balloon mitral valvuloplasty (PBMV) without surgical indications of mitral valve replacement (MVR). There was no blood leakage around the device by regular postoperative TEE and LAA radiography examinations. There were no complications of bleeding, embolism, or stroke through both at peri-operative period and at 1 month follow-up post procedure.</p><p><b>CONCLUSION</b>Preoperative Mimics 3D reconstruction of LAA by Mimics 3D imaging system among atrial fibrillation patients provides essential information guiding the successful LAA closures.</p>
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Adulto , Anciano , Anciano de 80 o más Años , Humanos , Persona de Mediana Edad , Anticoagulantes , Apéndice Atrial , Cirugía General , Fibrilación Atrial , Cirugía General , Procedimientos Quirúrgicos Cardíacos , Contraindicaciones , Ecocardiografía Transesofágica , Embolia , Imagenología Tridimensional , Prótesis e Implantes , Implantación de Prótesis , Accidente Cerebrovascular , Resultado del TratamientoRESUMEN
Objective To evaluate the clinical effects of Qufeng Jiedu Huoluo Decoction in treating the acute stage of periph-eral facial paralysis.Methods 60 cases of acute stage of peripheral facial paralysis were randomly divided into 2 groups,30 cases in each group.The two groups were treated by acupuncture.In addition the treatment group was added with oral Qufeng Jiedu Huoluo Decoction.Results The relief time of posterior auricular pain in the treatment group was shorter than that in the control group (P <0.05);the alleviation situation of the accompanying symptoms after 7 d and the neural function recovery situation after 14 d in the treatment group were superior to those in the control group (P < 0.05);the total effective rate in the treatment group was 93.3%,which was higher than 83.4% in the control group,the difference had statistical significance(P < 0.05).Conclusion Qufeng Jiedu Huoluo Decoction can effectively alleviate the clinical symptoms and signs of acute stage in peripheral facial paralysis.
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BACKGROUND:Inducing pluripotent stem cels has been considered as a promising treatment for ischemic heart disease. However, an ideal inducing method has not been found yet. OBJECTIVE:To investigate the role of sodium-calcium exchanger (NCX1) promoter in the differentiation of mouse induced pluriptent stem cels (miPS) into cardiomyocytes. METHODS: The pLVX-IRES-ZsGreen1 vectors which contain NCX1 promoter constructed by recombinant DNA technology were co-transfected to 293FT cels with ViraPowerTM Lentiviral Packaging Mix. The recombinant lentiviruses infected with miPS were selected and purified by puromycin. miPS were recovered and passaged to form embryoid bodies. The embryoid bodies were induced by differentiation medium containing various concentrations of the virus titer. The number of beating embryoid bodies were calculated. The expression profiles of the myocardial intra-markers were tested to determine the differentiation efficiency of iPSC by RT-PCR and immunofluorescence analysis. RESULTS AND CONCLUSION:pLVX-IRES-ZsGreen1 vectors which contain NCX1 promoter were constructed and confirmed by PCR. Virus could be packaged, purified and concentrated successfuly. The recombinant lentivirus to transduce miPS was sorted by flow cytometry. In contrast to NCX1-/GFP- cels, NCX1+/GFP+ cels were differentiated and developed prominent beating areas with sustained contractile activity for additional 4 days, and demonstrated positive expression of gap communication marker CX43 and cardiac troponin. The expressions of GATA4, MEF2c and Nkx2.5 in the NCX1+ cels were 4.2, 7.5, and 2.5 times those in NCX1- cels. Results showed the NCX1 promoter can promote the cardiac differentiation of miPS .
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Interferon beta (IFN-beta) and TNF-related apoptosis-inducing ligand (TRAIL) are effective anticancer agents. Adeno-associated virus (AAV) is one of the current most promising gene delivery vectors. Previously, we constructed tumor-targeting AAV-hTERT-IFN-beta and AAV-hTERT-TRAIL by inserting IFN-beta or TRAIL gene into AAV controlled by hTERT promoter. The studies showed that either single IFN-beta or TRAIL gene therapy exhibited a certain extent anticancer effect. Here, we report their inhibitory effects on A549 lung cancer cell growth in vitro and in vivo by combined AAV-hTERT-IFN-beta and AAV-hTERT-TRAIL. Expression of secreted IFN-beta in lung cancer A549 cells infected by AAV-hTERT-IFN-beta was detected by enzyme-linked immunosorbent assay (ELISA). The growth-suppressing effect of AAV-hTERT-IFN-beta in combination with AAV-hTERT-TRAIL on several cancer cell lines was assessed by MTT assay. Apoptosis of A549 cancer cells infected by AAV-hTERT-IFN-beta alone, AAV-hTERT-TRAIL alone, and their combination was evaluated by apoptotic cell staining and flow cytometry (FCM), respectively. The antitumor effect of the combination of AAV-hTERT-IFN-beta with AAV-hTERT-TRAIL in vivo was further evaluated through A549 lung cancer xenograft in nude mice. The results showed that the combinational treatment was superior to any alone and presented intensified tumor cytotoxic and apoptotic effect on A549 cancer cells. Most importantly, the combination of AAV-hTERT-IFN-beta with AAV-hTERT-TRAIL exhibited significant antitumor effect and eliminated all tumor masses in nude mice, which lay a foundation for exploring the molecular mechanisms of combined IFN-beta and TRAIL anti-tumor activity.
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Animales , Humanos , Ratones , Antineoplásicos , Metabolismo , Farmacología , Línea Celular Tumoral , Dependovirus , Genética , Metabolismo , Terapia Genética , Vectores Genéticos , Genética , Interferón beta , Genética , Farmacología , Neoplasias Pulmonares , Patología , Terapéutica , Ratones Desnudos , Trasplante de Neoplasias , Proteínas Recombinantes de Fusión , Genética , Farmacología , Ligando Inductor de Apoptosis Relacionado con TNF , Genética , FarmacologíaRESUMEN
Objective To investigate the protective effects of intra-peritoneal fluid resuscitation on small intestinal mucosa in rats with hemorrhagic shock. Method Fifty Sprague-Dawley (SD) rats were randomly (random number) divided into five groups, namely sham operation group (group I ), hemorrhagic shock group (group Ⅱ ), intra-venous fluid resuscitation group (group Ⅲ ) . intravenous fluid resuscitation plus intra-peritoneal saline resuscitation (group Ⅳ ) and intravenous fluid resuscitation plus intra-peritoneal PD-2 solution resuscitation group (group Ⅴ ). The rats of 5 groups were processed with cannulations of right common carotid artery, right femoral vein and left femoral artery with systemic heparinization. The rat models of hemorrhagic shock were established with modified Wigger' s method by which the blood exsanguinated from left femoral artery. The rats of group Ⅲ were resuscitated with shed blood plus twice equal volume of Ringer's solution after modeling of hemorrhagic shock.The rats of group Ⅳ and group Ⅴ were administered intra-peritoneally with 30 mL saline and 30 mL of 2.5% PD-2 solution, respectively as adjuncts to those used in the group Ⅲ . The specimens of blood and small intestine of rats of all groups were collected 60-120 minutes after modeling and resuscitation. The activity of plasma diamine oxidase (DAO) was determined with chromatometry, the level of plasma D-lactic acid (D-LA) with spectorophotometry and the level of plasma lipopolysaccharide (LPS) with nephelometry. The histopathological and ultrastructure changes of small intestine tissue of rats were observed under light microscope and electronic microscope. Results There were remarkable differences in activity of DAO, and the levels of D-LA and IPS in rats between those ingroup Ⅱ and group I (P <0.01), and between those in group V and groups Ⅱ , Ⅲ or Ⅳ (P <0.05 or P < 0.01) The pathomorphology and ultra-structure of small intestine tissues were severely damaged in group Ⅱ compared with those in group Ⅰ , and those markedly lessened in group V compared with groups Ⅱ , Ⅲ and Ⅳ . Conclusions Intraperitoneal fluid resuscitation with PD-2 solution can significantly protect the integrity of intestinal mucosa and the normal permeability of intestinal wall, and blunts the histopathological changes, and restrains bacterial translocation from gut and reduces the level of plasma endotoxin.
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@#ObjectiveTo explore the clinical diagnostic value of ambulatory EEG (AEEG) in epilepsy and atypical epilepsy.MethodsThe monitoring of 24-hour AEEG were performed in 67 epileptic and 53 atypical epileptic.Results65.7% of epileptic cases presented abnormality, and 34.0% of atypical epilepsy. The 85.5% of epileptic form discharges were found in the stage of sleep, especially in the Ⅰor Ⅱstage of NREM. The main epileptic form discharges was sharp waves.ConclusionThe monitoring of 24-hour AEEG may play important role in the diagnosis of epilepsy or atypical epilepsy, but can do little in the classification and detecting the focus of epilepsy.