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Carcinoma Ductal Pancreático/genética , Secuenciación del Exoma , Páncreas/patología , Neoplasias Pancreáticas/genética , Anciano , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/patología , Femenino , Perfilación de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patología , PronósticoRESUMEN
INTRODUCTION: Hypercalciuria, hypocitraturia and cystinuria are the most common underlying metabolic stone abnormalities in children. The present study compared stone growth patterns, stone burden, and the risk of stone-related surgery among these underlying metabolic conditions. METHODS: A retrospective cohort of 356 children with renal stones, followed from 2000 to 2015, was studied. Differences among metabolic groups were determined using Kruskal-Wallis test; the Scheffé-test was used for multiple comparisons to determine differences among single groups. Independent sample t-test was used when adequate, given the sample size, and Chi-squared test was used for categorical variables. Stone growth rates were calculated as differences in diameter divided by time elapsed between U/Ss (mm/year). Logistic regression was performed to assess the effect of initial stone size on the likelihood of surgery. RESULTS: Median stone size at presentation was significantly different among groups, with cystinuria being the group with the largest proportion of stones >10 mm, while patients with stones <5 mm were likely to have a normal metabolic workup (P < 0.05). Stones with a higher growth rate were found in the operative group, while slower growing stones were mostly managed conservatively (3.4 mm/year vs 0.8 mm/year, respectively; P = 0.014). However, stone growth rates were not significantly different among metabolic groups. On the other hand, the rate of new stone formation in cystinuric patients at their first follow-up was 30.4%, which was significantly higher than in patients with hypercalciuria (16.3%) or with a normal metabolic workup (17.2%; P < 0.05). Compared with stones <5 mm, stones measuring 5-10 mm were more than four times more likely to result in surgery, whereas the likelihood of surgery for 10-20 mm or >20 mm stones was almost 16 or 34 times, respectively (P < 0.001). CONCLUSIONS: It is believed that this is the first study to evaluate stone growth patterns, stone burden and surgical risk among children with hypercalciuria, hypocitraturia and cystinuria. Cystinuric patients presented with larger stones at the time of diagnosis, higher new stone formation rates, and were at higher risk of surgery. While no significant difference of growth rate was found among metabolic groups, stones with a higher growth rate were significantly more likely to result in surgical treatment than slower growing stones. Initial stone size, location of largest stone, previous urinary tract infection, and patient's metabolic type significantly influenced the likelihood of a surgical intervention. Better understanding of the natural history ultimately helps surgeons and clinicians defining prognosis, treatment, and prevention plans for pediatric urolithiasis.
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Cistinuria/complicaciones , Hipercalciuria/complicaciones , Cálculos Renales/patología , Cálculos Renales/cirugía , Urolitiasis/patología , Urolitiasis/cirugía , Adolescente , Niño , Preescolar , Cistinuria/patología , Femenino , Humanos , Hipercalciuria/patología , Cálculos Renales/etiología , Masculino , Selección de Paciente , Estudios Retrospectivos , Factores de Riesgo , Urolitiasis/etiologíaRESUMEN
OBJECTIVE: To evaluate the safety and efficacy of adjuvant intensity-modulated radiotherapy (IMRT) with concurrent paclitaxel and cisplatin (TP) in early stage cervical cancer patients with high risk factors after radical hysterectomy. METHODS: Patients who underwent radical hysterectomy for FIGO stage IB-IIA cervical cancer and had high risk factors for recurrence were recruited. One cycle of TP was delivered before and after concurrent chemoradiotherapy, respectively. Concurrent chemoradiotherapy began 21 days after the start of the initial cycle of the chemotherapy with two cycles of TP delivered on day 1 and day 29 of radiotherapy. Primary endpoints were overall survival (OS) and relapse-free survival (RFS), with toxicities, local-regional control (LC) and distant failure (DF) rate as secondary endpoints. RESULTS: Between 2008 and 2012, 67 patients were evaluable. The 2 and 4-year RFS rates were 98.2% and 92.9%. Corresponding OS rates were 100%, and 98.0%, respectively. The 4-year LC and DF rates were 98.0% and 5.2%, respectively. Grade 3-4 acute leucopenia, neutropenia and thrombocytopenia occurred in 25.4%, 11.9% and 1.5% of patients, respectively. There were 89.6% and 59.7% patients experienced acute vomiting and diarrhea, but only 6.0% and 6.0% patients were grade 3, respectively. No case of chronic toxicity exceeded grade 2. CONCLUSION: Adjuvant concurrent IMRT with paclitaxel plus cisplatin are safe and effective in early stage cervical cancer patients with high risk factors for recurrence following radical hysterectomy.
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Adenocarcinoma/terapia , Cisplatino/administración & dosificación , Estadificación de Neoplasias , Paclitaxel/administración & dosificación , Radioterapia de Intensidad Modulada/métodos , Neoplasias del Cuello Uterino/terapia , Adenocarcinoma/diagnóstico , Adenocarcinoma/mortalidad , Adulto , Antineoplásicos/administración & dosificación , China/epidemiología , Supervivencia sin Enfermedad , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Femenino , Humanos , Histerectomía , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia/tendencias , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/mortalidadRESUMEN
Confronted with the need to significantly raise the productivity of remotely located chemistry CROs Pfizer embraced a commitment to continuous improvement which leveraged the tools from both Lean Six Sigma and queue management theory to deliver positive measurable outcomes. During 2012 cycle times were reduced by 48% by optimization of the work in progress and conducting a detailed workflow analysis to identify and address pinch points. Compound flow was increased by 29% by optimizing the request process and de-risking the chemistry. Underpinning both achievements was the development of close working relationships and productive communications between Pfizer and CRO chemists.
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Servicios Contratados/organización & administración , Industria Farmacéutica/organización & administración , Investigación/organización & administración , Química Farmacéutica/métodos , Comunicación , Servicios Contratados/normas , Diseño de Fármacos , Descubrimiento de Drogas/métodos , Industria Farmacéutica/normas , Eficiencia Organizacional , Humanos , Mejoramiento de la Calidad , Investigación/normas , Flujo de TrabajoRESUMEN
Medicinal plants have been a source of succour in the control of many diseases in developing countries and anaemia is no exception. In this study, ethnomedical survey was carried out for recording medicinal plants used in Northern and South-Eastern Côte d'Ivoire against anaemia. Also iron content was determined for some of the recorded plants using phenanthroline method. Thirty (30) medicinal plants, covering 28 genera and 22 families were recorded. These plants were used to prepare 30 receipts for the treatment of anaemia and aggravating factors such as malaria and gastro-intestinal helminthes. Eleven (11) of these medicinal plants showed presence of iron in various quantities. The most promising were Tectona grandis, Amaranthus spinosus and Stylosanthes erecta which contained the highest iron contents viz; 266.6, 236.6 and 206.6 mg/100 g respectively. They were followed by Hoslundia opposita, Imperata cylindrica, Cajanus cajan, Thalia geniculata and Milicia excelsa. These results lend credence to the traditional use of these plants in Cote d'Ivoire's ethnomedicine for the treatment of anaemia.
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Anemia/tratamiento farmacológico , Hierro/análisis , Magnoliopsida/química , Medicinas Tradicionales Africanas , Fitoterapia , Extractos Vegetales/uso terapéutico , Plantas Medicinales/química , Adulto , Anciano , Anemia/complicaciones , Côte d'Ivoire , Enfermedades Gastrointestinales/complicaciones , Enfermedades Gastrointestinales/parasitología , Humanos , Malaria/complicaciones , Persona de Mediana Edad , Extractos Vegetales/químicaRESUMEN
Chemokine receptors are critical regulators of cell migration in the context of immune surveillance, inflammation, and development. The G protein-coupled chemokine receptor CXCR4 is specifically implicated in cancer metastasis and HIV-1 infection. Here we report five independent crystal structures of CXCR4 bound to an antagonist small molecule IT1t and a cyclic peptide CVX15 at 2.5 to 3.2 angstrom resolution. All structures reveal a consistent homodimer with an interface including helices V and VI that may be involved in regulating signaling. The location and shape of the ligand-binding sites differ from other G protein-coupled receptors and are closer to the extracellular surface. These structures provide new clues about the interactions between CXCR4 and its natural ligand CXCL12, and with the HIV-1 glycoprotein gp120.
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Receptores CXCR4/química , Animales , Línea Celular , Quimiocina CXCL12 , Cristalografía por Rayos X , Proteína gp120 de Envoltorio del VIH/metabolismo , Humanos , Proteínas de la Membrana , Modelos Moleculares , Unión Proteica , Conformación Proteica , Multimerización de Proteína , Receptores CXCR4/antagonistas & inhibidores , Receptores CXCR4/metabolismo , Proteínas Recombinantes/química , Spodoptera , Tiourea/análogos & derivados , Tiourea/químicaRESUMEN
Synthesis and structure-activity relationship (SAR) studies on 5-trifluoromethylpyrido[4,3-d]pyrimidin-4(3H)-ones, a novel class of calcium receptor antagonists is described with particular emphasis on optimization of the pharmacokinetic/pharmacodynamic parameters required for a short duration of action compound. Orally-active compounds were identified which displayed the desired animal pharmacology (rapid and transient stimulation of parathyroid hormone) essential for bone anabolic effects.
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Anabolizantes/química , Pirimidinonas/química , Receptores Sensibles al Calcio/antagonistas & inhibidores , Administración Oral , Anabolizantes/administración & dosificación , Anabolizantes/farmacocinética , Animales , Masculino , Hormona Paratiroidea/metabolismo , Pirimidinonas/administración & dosificación , Pirimidinonas/farmacocinética , Ratas , Ratas Sprague-Dawley , Receptores Sensibles al Calcio/metabolismo , Relación Estructura-ActividadRESUMEN
The synthesis and SAR for a series of diaminopyrimidines as PYK2 inhibitors are described. Using a combination of library and traditional medicinal chemistry techniques, a FAK-selective chemical series was transformed into compounds possessing good PYK2 potency and 10- to 20-fold selectivity against FAK. Subsequent studies found that the majority of the compounds were positive in a reactive metabolite assay, an indicator for potential toxicological liabilities. Based on the proposed mechanism for bioactivation, as well as a combination of structure-based drug design and traditional medicinal chemistry techniques, a follow-up series of PYK2 inhibitors was identified that maintained PYK2 potency, FAK selectivity and HLM stability, yet were negative in the RM assay.
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Quinasa 2 de Adhesión Focal/antagonistas & inhibidores , Pirimidinas/síntesis química , Pirimidinas/farmacología , Animales , Técnicas Químicas Combinatorias , Cristalografía por Rayos X , Modelos Animales de Enfermedad , Diseño de Fármacos , Proteína-Tirosina Quinasas de Adhesión Focal/antagonistas & inhibidores , Humanos , Conformación Molecular , Estructura Molecular , Osteoporosis/tratamiento farmacológico , Pirimidinas/química , Ratas , Relación Estructura-ActividadRESUMEN
Preclinical and clinical studies have demonstrated that a free radical scavenger edaravone has neuroprotective effects on ischemic stroke but the underlying mechanism is not fully understood. The aim of this research is to explore the effect of edaravone on the apoptotic process involving the Fas/FasL signaling pathway. Transient focal ischemia in rats was induced for 2 hours by middle cerebral artery occlusion (MCAO). After reperfusion rats were treated i.v. with either edaravone or physiological saline. The expression of Fas-associated death domain protein (FADD), death-associated protein (Daxx) and caspase-8 was examined by immunohistochemistry. The mRNA levels for FADD and Daxx by reverse-transcriptase PCR (RT-PCR) and apoptosis was assessed by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL). Neurological scores and infarction volumes were also evaluated. Edaravone significantly improved the neurological outcome (p<0.05) and reduced the total infarct volumes (p<0.05), compared with saline control. In addition, edaravone-treatment significantly reduced the number of TUNEL-positive cells (p<0.01), reduced expression levels of FADD, Daxx and caspase-8 immunoreactivity (p <0.05 approximately 0.01), and decreased mRNA levels of FADD and Daxx (p<0.05 approximately 0.01) within the peri-infarct area. We conclude that edaravone may protect ischemic neurons from apoptosis via suppressing the gene expression of the Fas/FasL signaling pathway.
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Antipirina/análogos & derivados , Proteínas Adaptadoras de Señalización del Receptor del Dominio de Muerte/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Ataque Isquémico Transitorio/tratamiento farmacológico , Fármacos Neuroprotectores/uso terapéutico , Transducción de Señal/efectos de los fármacos , Animales , Antipirina/uso terapéutico , Fragmentación del ADN/efectos de los fármacos , Modelos Animales de Enfermedad , Edaravona , Etiquetado Corte-Fin in Situ , Ataque Isquémico Transitorio/fisiopatología , Masculino , Examen Neurológico , Ratas , Ratas Sprague-Dawley , Estadísticas no ParamétricasRESUMEN
[Structure: see text] 12-hydroxydaphnetoxins, members of the structurally fascinating daphnane diterpene family, exhibit a wide range of significant biological activities. A general route to the BC-ring system of 12-hydroxy daphnetoxins is reported based on D-ribose. Depending on the choice of protecting groups and solvent, the oxidopyrylium-alkene [5+2] cycloaddition originating from A provides cycloadduct diastereomer B or C with good to excellent selectivity.
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Hidrocarburos Aromáticos con Puentes/síntesis química , Diterpenos/síntesis química , Ciclización , Estructura MolecularRESUMEN
Macrocycle 1 is a new highly potent analogue of bryostatin 1, a promising anti-cancer agent currently in human clinical trials. In vitro, 1 displays picomolar affinity for PKC and exhibits over 100-fold greater potency than bryostatin 1 when tested against various human cancer cell lines. Macrocycle 1 can be generated in clinically required amounts by chemical synthesis in only 19 steps (LLS) and represents a new clinical lead for the treatment of cancer.
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Antineoplásicos/síntesis química , Lactonas/síntesis química , Antineoplásicos/metabolismo , Antineoplásicos/farmacología , Brioestatinas , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Lactonas/metabolismo , Lactonas/farmacología , Macrólidos , Proteína Quinasa C/metabolismo , Células Tumorales CultivadasRESUMEN
[reaction: see text] A concise asymmetric synthesis of the tricyclic core of cyathane diterpenes is described, based on a novel transition-metal-catalyzed intramolecular [5 + 2] cycloaddition of ynone-vinylcyclopropane 10 (assembled from commercially available (S)-(-)-limonene), which proceeds in 90% yield with >95% selectivity. This strategy provides efficient access (14 steps and 13% overall yield) to potential analogues as well as precursors of nerve growth factor (NGF)-inducing diterpenes.
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Diterpenos/síntesis química , Ciclohexenos , Diterpenos/química , Diterpenos/farmacología , Limoneno , Factor de Crecimiento Nervioso/efectos de los fármacos , Factor de Crecimiento Nervioso/metabolismo , Terpenos/químicaRESUMEN
The dbl oncogene encodes a prototype member of the Rho GTPase guanine nucleotide exchange factor (GEF) family. Oncogenic activation of proto-Dbl occurs through truncation of the N-terminal 497 residues. The C-terminal half of proto-Dbl includes residues 498 to 680 and 710 to 815, which fold into the Dbl homology (DH) domain and the pleckstrin homology (PH) domain, respectively, both of which are essential for cell transformation via the Rho GEF activity or cytoskeletal targeting function. Here we have investigated the mechanism of the apparent negative regulation of proto-Dbl imposed by the N-terminal sequences. Deletion of the N-terminal 285 or C-terminal 100 residues of proto-Dbl did not significantly affect either its transforming activity or GEF activity, while removal of the N-terminal 348 amino acids resulted in a significant increase in both transformation and GEF potential. Proto-Dbl displayed a mostly perinuclear distribution pattern, similar to a polypeptide derived from its N-terminal sequences, whereas onco-Dbl colocalized with actin stress fibers, like the PH domain. Coexpression of the N-terminal 482 residues with onco-Dbl resulted in disruption of its cytoskeletal localization and led to inhibition of onco-Dbl transforming activity. The apparent interference with the DH and PH functions by the N-terminal sequences can be rationalized by the observation that the N-terminal 482 residues or a fragment containing residues 286 to 482 binds specifically to the PH domain, limiting the access of Rho GTPases to the catalytic DH domain and masking the intracellular targeting function of the PH domain. Taken together, our findings unveiled an autoinhibitory mode of regulation of proto-Dbl that is mediated by the intramolecular interaction between its N-terminal sequences and PH domain, directly impacting both the GEF function and intracellular distribution.
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Proteínas Proto-Oncogénicas/química , Proteínas Proto-Oncogénicas/metabolismo , Células 3T3 , Actinas/metabolismo , Animales , Western Blotting , Células COS , Dominio Catalítico , Línea Celular , Núcleo Celular/metabolismo , Citoesqueleto/metabolismo , ADN Complementario/metabolismo , Activación Enzimática , Escherichia coli/metabolismo , Eliminación de Gen , Glutatión Transferasa/metabolismo , Factores de Intercambio de Guanina Nucleótido/metabolismo , Guanosina Difosfato/metabolismo , Guanosina Trifosfato/metabolismo , Insectos , Ratones , Microscopía Fluorescente , Mutagénesis Sitio-Dirigida , Pruebas de Precipitina , Estructura Terciaria de Proteína , Proteínas Recombinantes/metabolismo , Fibras de Estrés/metabolismo , Factores de Tiempo , Transfección , Proteína de Unión al GTP cdc42/metabolismo , Proteínas de Unión al GTP rho/metabolismoRESUMEN
The dbl oncogene product (onco-Dbl) is the prototype member of a family of guanine nucleotide exchange factors (GEFs) for Rho GTPases. The Dbl homology (DH) domain of onco-Dbl is responsible for the GEF catalytic activity, and the DH domain, together with the immediately adjacent pleckstrin homology (PH) domain, constitutes the minimum module bearing transforming function. In the present study, we demonstrate that the onco-Dbl protein exists in oligomeric form in vitro and in cells. The oligomerization is mostly homophilic in nature and is mediated by the DH domain. Mutagenesis studies mapped the region involved in oligomerization to the conserved region 2 of the DH domain, which is located at the opposite side of the Rho GTPase interacting surface. Residue His556 of this region, in particular, is important for this activity, since the H556A mutant retained the GEF catalytic capability and the binding activity toward Cdc42 and RhoA in vitro but was deficient in oligomer formation. Consequently, the Rho GTPase activating potential of the H556A mutant was significantly reduced in cells. The focus-forming and anchorage-independent growth activities of onco-Dbl were completely abolished by the His556-to-Ala mutation, whereas the abilities to stimulate cell growth, activate Jun N-terminal kinase, and cause actin cytoskeletal changes were retained by the mutant. The ability of onco-Dbl to oligomerize allowed multiple Rho GTPases to be recruited to the same signaling complex, and such an ability is defective in the H556A mutant. Taken together, these results suggest that oligomerization of onco-Dbl through the DH domain is essential for cellular transformation by providing the means to generate a signaling complex that further augments and/or coordinates its Rho GTPase activating potential.
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Transformación Celular Neoplásica , Proteínas Oncogénicas de Retroviridae/química , Proteínas Oncogénicas de Retroviridae/metabolismo , Células 3T3 , Actinas/metabolismo , Animales , División Celular , Citoesqueleto/metabolismo , Activación Enzimática , Factores de Intercambio de Guanina Nucleótido/metabolismo , Proteínas Quinasas JNK Activadas por Mitógenos , Cinética , Ratones , Microscopía Fluorescente , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Modelos Moleculares , Mutagénesis Sitio-Dirigida , Mutación/genética , Unión Proteica , Estructura Cuaternaria de Proteína , Estructura Terciaria de Proteína , Proteínas Recombinantes de Fusión , Proteínas Oncogénicas de Retroviridae/genética , Transducción de Señal , Transfección , Proteína de Unión al GTP cdc42/metabolismo , Proteínas de Unión al GTP rho/genética , Proteínas de Unión al GTP rho/metabolismoRESUMEN
The c-erbB-2/neu-encoded protein p185 is closely related to the growth and metastasis of adenocarcinoma. We sought to reverse the malignant phenotype of gastric cancer cell line SGC7901 with c-erbB-2-specific ribozyme. We designed the ribozyme and generated the in vitro transcription vectors of the ribozyme and its substrate. In vitro cleavage reaction indicated that the ribozyme catalyzed 79.3% target RNA in 1 hour at 37 degrees C. Then, we generated the eucaryotic expression vectors of the ribozyme and transfected them into SGC7901 cells, which highly express p185. Analyses showed that the c-erbB-2 mRNA and p185 were reduced remarkably in the ribozyme-transfected cells. The growth rate of the ribozyme-transfected cells was much lower than that of the control group. Tumorigenicity was also decreased dramatically in nude mice. The results demonstrated that c-erbB-2-specific ribozyme may inhibit the malignancy of gastric cancer cells SGC7901.
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Adenocarcinoma/terapia , Genes erbB-2/genética , ARN sin Sentido/uso terapéutico , ARN Catalítico/uso terapéutico , Neoplasias Gástricas/terapia , Adenocarcinoma/genética , Adenocarcinoma/patología , Animales , Secuencia de Bases , Femenino , Terapia Genética , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Datos de Secuencia Molecular , Fenotipo , Plásmidos , ARN Catalítico/genética , ARN Mensajero/antagonistas & inhibidores , ARN Mensajero/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Transfección , Células Tumorales CultivadasRESUMEN
[reaction--see text] This paper describes a catalytic, asymmetric approach to the C(1)(')-C(10)(') segment of pamamycin 621A. We synthesize this segment in a convergent manner, with each of the coupling partners ultimately deriving from enantiomerically enriched methylketene dimer.
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Antifúngicos/química , Antibacterianos/síntesis química , Antibacterianos/química , Antifúngicos/síntesis química , Antituberculosos/síntesis química , Antituberculosos/química , Catálisis , Macrólidos , Compuestos Orgánicos , EstereoisomerismoRESUMEN
OBJECTIVE: To construct in vitro transcription vectors of genes of c-erbB-2 specific ribozyme and its substrate and to probe its in vitro cleavage action. METHODS: According to the computer design, a specific restriction site EcoR V was added to the 3' end of the ribozyme gene (RZ1). Then, the RZ1 gene and its substrate gene were cloned into the in vitro transcription vector pGEM3Zf(-) separately. The recombinants containing RZ1 gene were first screened by agrose ge1 electrophoresis through EcoR V digestion and was identified by automatic sequencing. The products of in vitro transcription were labeled with 32P. In vitro cleavage reaction was performed at 37 degrees C for 1 h under the presence of Mg++. The cleavage product was analyzed by polyacrilamide gel electrophoresis. After autoradiography, the cleavage rate was counted by image analysis. RESULTS: The recombinants containing the RZ1 gene were successfully selected by the EcoR V digestion and were designated as pGM3Z-RZ1. The automatic sequence analysis proved that the synthesized RZ1 gene was correct. The target gene was also cloned into the pGEM3Zf(-) under SP6 promoter. After in vitro transcription, the cleavage reaction was shown to have cut off 79.3% target RNA in 1 h. CONCLUSION: The c-erbB-2 oncogene-specific ribozyme has a high activity in vitro. It lays a foundation for the study of the therapeutic use of ribozyme in gene therapy of cancer.
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Genes erbB-2 , ARN Catalítico/farmacología , Terapia Genética , ARN Catalítico/uso terapéuticoRESUMEN
OBJECTIVE: To probe the effect of c-erbB-2 specific ribozyme to the malignant phenotype of gastric cancer. METHODS: The eucaryotic expression vector of c-erbB-2 specific ribozyme RZ1 was designed by computer and named pDOR-RZ1. The transfection of the gastric cancer cell line SGC-7901 was mediated by Lipofect AMINE. Flow cytometry was used to analyse the expression of the c-erbB-2 product P185. In vivo study of tumorogenecity of the transfected cells was performed in nude mice. RESULTS: pDOR-RZ1 was successfully transfected into the gastric cancer cell line SGC-7901 and then the single clones were selected by G418 and named SGC/RZ1. Flow cytometry analysis showed that the expression of P185 was suppressed by 62.7%. The growth rate of SGC/RZ1 was inhibited by 55%. The tumor-forming time in SGC/RZ1 in nude mice was delayed remarkably and the tumor size was also much smaller than that in the control group, indicating the inhibition of the tumorogenecity of SGC/RZ1 in nude mice. CONCLUSION: c-erbB-2 specific ribozyme is very efficient in reversing the malignant phenotype of gastric cancer. This might provide a new approach for gene therapy of gastric cancer.
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Receptor ErbB-2/biosíntesis , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Animales , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Fenotipo , ARN Catalítico/biosíntesis , ARN Catalítico/genética , Receptor ErbB-2/genética , Transfección , Células Tumorales CultivadasRESUMEN
The separation of stereoisomers of 14 pyrethroids has been studied by capillary gas chromatography. The pyrethroids are cypermethrin (P1), phenothrin (P2), allethrin (P3), prallethrin (P4), tetramethrin (P5), permethrin (P6), cyfluthrin (P7), fenvalerate (P8), flucythrinate (P9), bromofenvalerate (P10), fluvalinate (P11), methothrin (P12), resmethrin (P13) and py115 (P14). The gas chromatographic conditions were as follows. Column 1: fused silica, 10m x 0.53mm x 1.0microm film (QF-1); columntemperature: 180 degrees C-260 degrees C depending on the pyrethroids analysed; the temperature of injector and detector: 280 degrees C; carrier gas: H2 4.6mL/min; detector: FID; spilt ratio: 5:1, sample size 1.0 L. The stereoisomers of P2, P3, P4, P5, P6, P8, P9, P10, P12 and P10 can be completely separated by QF-1 column. However the stereoisomers of P11 can not be separated and the three peaks of P1 and P7 have been only separated by column 1. In comparing with packed column of QF-1, there are advantages in superior resolution, lower oven temperature and shorter analysis time for capillary column of QF-1. Column 2: fused silica HP-5 (crosslinked 5% phenyl methyl silicone) 25m x 0.32mm x 1.0microm film; column temperature: P1 and P7 250 degrees C, P11 260 degrees C, and P14 200 degrees C; carrier gas: H2 2.6mL/min. Other conditions were the same as the column 1 described. The stereoisomers of P1, P7, P11 and P14 can be separated, but the separation of stereoisomers was not sufficient. The stereoisomers of P2, P5, P6, P8, P9, P10, P12 and P13 can be completely separated by HP-5 capillary column. However separation on the HP-5 capillary column is not sufficient for diastereoisomers of P3 and P4.