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排序方式: 共有8467条查询结果,搜索用时 31 毫秒
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Ricardo Cambraia Parreira Diana Paola Gmez‐Mendoza Itamar Couto Guedes de Jesus Rafael Pereira Lemos Anderson Kennedy Santos Cristiana Perdigo Rezende Henrique Csar Pereira Figueiredo Mauro Cunha Xavier Pinto Frank Kjeldsen Silvia Guatimosim Rodrigo Ribeiro Resende Thiago Verano‐Braga 《Proteomics. Clinical applications》2020,14(4)
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HSDPA的度理论上最高达4.4M bit/s,但额的流量对无线接网络和空载传输容量要求有巨大影响。“3G的势头已经成为一个始终如一的主题。不过,正如我们所指出的,对3G手机的深刻领会并不总是伴随着对3G服务的持续理解。看上去高速下行包接入(HSDPA)技术可能是一个例外。它在欧洲发布,并且已经引起了人们浓厚的兴趣。看看它在亚洲的发展,我们不禁要问:它就是最终真正的3G吗?回首2002~2003年,HSDPA的部署看上去是一条漫长的道路,并且3GPP方面没有什么紧迫感,它的成员忙于应付WCDMA部署方面的复杂性。两件事的发生加速了HSDPA的部署:… 相似文献
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SH Kaufmann D Peereboom CA Buckwalter PA Svingen LB Grochow RC Donehower EK Rowinsky 《Canadian Metallurgical Quarterly》1996,88(11):734-741
BACKGROUND: Topotecan (TPT) is a topoisomerase I poison that exhibits antineoplastic activity. Analysis of the cytotoxic effects of combinations of TPT and other anticancer agents has been limited. PURPOSE: We assessed the cytotoxic effects produced by combinations of TPT and other antineoplastic agents in experiments involving multiple human cancer cell lines of diverse histologic origins. METHODS: The cytotoxic effects of various antimetabolites (fluorouracil, methotrexate, or cytarabine), antimicrotubule agents (vincristine or paclitaxel [Taxol]), DNA alkylating agents (melphalan, bis[chloroethyl]nitrosourea [BCNU], or 4-hydroperoxycyclophosphamide [4HC]), and a DNA-platinating agent (cisplatin), alone and in combination with TPT, were measured in clonogenic (i.e., colony-forming) assays. HCT8 ileocecal adenocarcinoma, A549 non-small-cell lung carcinoma, NCI-H82ras(H) lung cancer, T98G glioblastoma, and MCF-7 breast cancer cell lines were used in these assays. The data were analyzed by the median effect method, primarily under the assumption that drug mechanisms of action were mutually nonexclusive (i.e., completely independent of one another). For each level of cytotoxicity (ranging from 5% to 95%), a drug combination index (CI) was calculated. A CI less than 1 indicated synergy (i.e., the effect of the combination was greater than that expected from the additive effects of the component agents), a CI equal to 1 indicated additivity, and a CI greater than 1 indicated antagonism (the effect of the combination was less than that expected from the additive effects of the component agents). RESULTS: When the mechanisms of drug action were assumed to be mutually nonexclusive, virtually all CIs for combinations of TPT and either antimetabolites or antimicrotubule agents revealed cytotoxic effects that were less than additive. The CIs calculated at low-to-intermediate levels of cytotoxicity for combinations of TPT and the DNA alkylating agents melphalan, BCNU, and 4HC also showed drug effects that were less than additive; in most cases, however, nearly additive or even synergistic effects were observed with these same drug combinations at high levels of cytotoxicity (i.e., at > or = 90% inhibition of colony formation). Results obtained with combinations of TPT and cisplatin varied according to the cell line examined. With A549 cells, less than additive effects were seen at low-to-intermediate levels of cytotoxicity, and more than additive effects were seen at high levels of cytotoxicity. With NCI-H82ras(H) cells, synergy was observed over most of the cytotoxicity range. CONCLUSIONS AND IMPLICATIONS: TPT cytotoxicity appears to be enhanced more by combination with certain DNA-damaging agents than by combination with antimetabolites or antimicrotubule agents. Interactions between TPT and other drugs can vary depending on the cell type examined. Further investigation is required to determine the basis of the observed effects and to determine whether these in vitro findings are predictive of results obtained in vivo. 相似文献
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Antisense oligonucleotide inhibition of hepatitis C virus gene expression in transformed hepatocytes
R Hanecak V Brown-Driver MC Fox RF Azad S Furusako C Nozaki C Ford H Sasmor KP Anderson 《Canadian Metallurgical Quarterly》1996,70(8):5203-5212
Genetic and biochemical studies have provided convincing evidence that the 5' noncoding region (5' NCR) of hepatitis C virus (HCV) is highly conserved among viral isolates worldwide and that translation of HCV is directed by an internal ribosome entry site (IRES) located within the 5' NCR. We have investigated inhibition of HCV gene expression using antisense oligonucleotides complementary to the 5' NCR, translation initiation codon, and core protein coding sequences. Oligonucleotides were evaluated for activity after treatment of a human hepatocyte cell line expressing the HCV 5' NCR, core protein coding sequences, and the majority of the envelope gene (E1). More than 50 oligonucleotides were evaluated for inhibition of HCV RNA and protein expression. Two oligonucleotides, ISIS 6095, targeted to a stem-loop structure within the 5' NCR known to be important for IRES function, and ISIS 6547, targeted to sequences spanning the AUG used for initiation of HCV polyprotein translation, were found to be the most effective at inhibiting HCV gene expression. ISIS 6095 and 6547 caused concentration-dependent reductions in HCV RNA and protein levels, with 50% inhibitory concentrations of 0.1 to 0.2 microM. Reduction of RNA levels, and subsequently protein levels, by these phosphorothioate oligonucleotides was consistent with RNase H cleavage of RNA at the site of oligonucleotide hybridization. Chemically modified HCV antisense phosphodiester oligonucleotides were designed and evaluated for inhibition of core protein expression to identify oligonucleotides and HCV target sequences that do not require RNase H activity to inhibit expression. A uniformly modified 2'-methoxyethoxy phosphodiester antisense oligonucleotide complementary to the initiator AUG reduced HCV core protein levels as effectively as phosphorothioate oligonucleotide ISIS 6095 but without reducing HCV RNA levels. Results of our studies show that HCV gene expression is reduced by antisense oligonucleotides and demonstrate that it is feasible to design antisense oligonucleotide inhibitors of translation that do not require RNase H activation. The data demonstrate that chemically modified antisense oligonucleotides can be used as tools to identify important regulatory sequences and/or structures important for efficient translation of HCV. 相似文献
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PE Sipila VJ Wiebe GB Hubbard SK Koester VD Emshoff JU Maenpaa GT Wurz RC Seymour MW DeGregorio 《Canadian Metallurgical Quarterly》1993,(15):2138-2144
The effects of long-term tamoxifen exposure on cell growth and cell cycle kinetics were compared between oestrogen receptor (ER)-positive (MCF-7) and ER-negative (MDA-MB-231) cell lines. In the MCF-7 cell line, prolonged tamoxifen exposure (0.5 mumol/l for > 100 days) blocked cells in G0-G1 of the cell cycle, and slowed the doubling time of cells from 30 to 59 h. These effects corresponded to an increase in the cellular accumulation of tamoxifen over time [mean area under concentration curve (AUC) = 77.92 mumoles/10(6)/cells/day]. In contrast, in the MDA-MB-231 cell line, long-term tamoxifen exposure had no obvious effect on the doubling time, and reduced cellular tamoxifen accumulation (mean AUC = 50.50 mumoles/10(6)/cells/day) compared to the MCF-7 cells. Flow cytometric analysis of MDA-MB-231 cells demonstrated that a new tetraploid clone emerged following 56 days of tamoxifen exposure. Inoculation of the MDA-MB-231 tetraploid clone and MDA-MB-231 wildtype cells into the opposite flanks of athymic nude mice resulted in the rapid growth of tetraploid tumours. The tetraploid tumours maintained their ploidy following tamoxifen treatment for nine consecutive serial transplantations. Histological examination of the fifth transplant generation xenografts revealed that the tetraploid tumour had a 25-30 times greater mass, area of haemorrhage and necrosis, a slightly higher mitotic index and was more anaplastic than the control neoplasm. The control wildtype MDA-MB-231 tumours maintained a stable ploidy following tamoxifen treatment until the eighth and ninth transplantation, when a tetraploid population appeared, suggesting that tamoxifen treatment may select for this clone in vivo. These studies suggest that prolonged tamoxifen exposure may select for new, stable, fast growing cell clones in vitro as well as in vivo. 相似文献
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Dynamic cardiomyoplasty (DCM) involves the electrical stimulation of a pedicled latissimus dorsi muscle flap wrapped around the falling ventricle as a means of cardiac assist. To further elucidate a potential neurohumoral mechanism for improvement of cardiac output after myoplasty, we evaluated the hemodynamic effects of in situ stimulation of the latissimus dorsi muscle (in the absence of cardiomyoplasty). In seven mongrel dogs, a nerve cuff electrode (Medtronic 6901) was placed around the left thoracodorsal nerve (TDN). This was attached to a pulse generator (Medtronic, Itrel 7420), delivering a 4.0 volt, 0.19 second on, 0.81 second off, 33 Hz, 210 microsecond pulse width, cyclic bursts similar to that used in DCM. Stroke volume index (SVI) and other hemodynamic parameters as well as plasma norepinephrine (NE) levels were measured at five stages: baseline, stimulator on at 0, 2, and 5 minutes, and stimulator off at 30 minutes after. The animals were then subjected to 4 weeks of rapid pacing at 240 beats/min (Medtronic 8329) to induce heart failure, and as the rapid pacing was discontinued, measurements were repeated as above. After rapid pacing, cardiac function was significantly depressed, and NE was elevated (133 +/- 69 versus 500 +/- 353 pg/mL, p < 0.05). In the normal hearts, TDN stimulation increased SVI, heart rate, systemic pressure, and NE levels. In heart failure, however, no significant changes in cardiac function and NE levels were noted. In conclusion, our data indicate that in the normal hearts, afferent impulses from TDN stimulation alone may augment cardiac function by means of a neurohumoral effect that is not seen in severe heart failure. The implications of these findings in DCM are discussed. 相似文献
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MA Steller KJ Gurski M Murakami RW Daniel KV Shah E Celis A Sette EL Trimble RC Park FM Marincola 《Canadian Metallurgical Quarterly》1998,4(9):2103-2109
Human papillomavirus (HPV) infection has been causally associated with cervical cancer. We tested the effectiveness of an HLA-A*0201-restricted, HPV-16 E7 lipopeptide vaccine in eliciting cellular immune responses in vivo in women with refractory cervical cancer. In a nonrandomized Phase I clinical trial, 12 women expressing the HLA-A2 allele with refractory cervical or vaginal cancer were vaccinated with four E786-93 lipopeptide inoculations at 3-week intervals. HLA-A2 subtyping was also performed, and HPV typing was assessed on tumor specimens. Induction of epitope-specific CD8+ T-lymphocyte (CTL) responses was analyzed using peripheral blood leukapheresis specimens obtained before and after vaccination. CTL specificity was measured by IFN-gamma release assay using HLA-A*0201 matched target cells. Clinical responses were assessed by physical examination and radiographic images. All HLA-A*0201 patients were able to mount a cellular immune response to a control peptide. E786-93-specific CTLs were elicited in 4 of 10 evaluable HLA-A*0201 subjects before vaccination, 5 of 7 evaluable HLA-A*0201 patients after two vaccinations, and 2 of 3 evaluable HLA-A*0201 cultures after all four inoculations. Two of three evaluable patients' CTLs converted from unreactive to reactive after administration of all four inoculations. There were no clinical responses or treatment toxicities. The ability to generate specific cellular immune responses is retained in patients with advanced cervical cancer. Vaccination with a lipidated HPV peptide epitope appears capable of safely augmenting CTL reactivity. Although enhancements of cellular immune responses are needed to achieve therapeutic utility in advanced cervical cancer, this approach might prove useful in treating preinvasive disease. 相似文献