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排序方式: 共有1064条查询结果,搜索用时 31 毫秒
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Sebastian Mondaca Walid K. Chatila David Bates Jaclyn F. Hechtman Andrea Cercek Neil H. Segal Zsofia K. Stadler Anna M. Varghese Ritika Kundra Marinela Capanu Jinru Shia Nikolaus Schultz Leonard Saltz Rona Yaeger 《Clinical colorectal cancer》2019,18(1):e39-e52
Background
Treatment of advanced anal squamous cell cancer (SCC) is usually with the combination of cisplatin and 5-fluorouracil, which is associated with heterogeneous responses across patients and significant toxicity. We examined the safety and efficacy of a modified schedule, FOLFCIS (leucovorin, fluorouracil, and cisplatin), and performed an integrated clinical and genomic analysis of anal SCC.Patients and Methods
We reviewed all patients with advanced anal SCC receiving first-line FOLFCIS chemotherapy – essentially a FOLFOX (leucovorin, fluorouracil, and oxaliplatin) schedule with cisplatin substituted for oxaliplatin – in our institution between 2007 and 2017, and performed deep sequencing to identify genomic markers of response and key genomic drivers.Results
Fifty-three patients with advanced anal SCC (48 metastatic; 5 unresectable, locally advanced) received first-line FOLFCIS during this period; all were platinum-naive. The response rate was 48% (95% confidence interval [CI], 32.6%-63%). With a median follow-up of 41.6 months, progression-free survival and overall survival were 7.1 months (95% CI, 4.4-8.6 months) and 22.1 months (95% CI, 16.9-28.1 months), respectively. Among all patients with advanced anal SCC that underwent sequencing during the study period, the most frequent genomic alterations consisted of chromosome 3q amplification (51%) and mutations in PIK3CA (29%) and KMT2D (22%). No genomic alteration correlated with response to platinum-containing treatment. Although there were few cases, patients with human papillomavirus-negative anal SCC did not appear to benefit from FOLFCIS, and all harbored distinct genomic profiles with TP53, TERT promoter, and CDKN2A mutations.Conclusions
FOLFCIS appears effective and safe as first-line chemotherapy in patients with advanced anal SCC and represents an alternative treatment option for these patients. 相似文献4.
Using bladder instillations to manage indwelling catheters 总被引:2,自引:0,他引:2
Pomfret I Bayait F Mackenzie R Wells M Winder A 《British journal of nursing (Mark Allen Publishing)》2004,13(5):261-267
Indwelling urinary catheters are commonly used in both acute and primary care settings but patients often experience problems with blockage of the catheter as a result of encrustation. Bladder instillations of differing solutions are used in an attempt to prevent and treat this problem of encrustation. This article looks at some of the issues surrounding the use and methods of these solutions. Based on an audit performed by a group of continence clinical nurse specialists in five areas of the UK, results of a questionnaire sent to acute and primary care nursing staff in 2003 are presented and discussed. The questionnaire covered a variety of clinical issues involved in performing bladder instillations and the results show that there is a wide variation of practice across the UK. The authors conclude that there are issues pertaining to bladder instillations which warrant further work. 相似文献
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OBJECTIVE: Since apoptosis is an important contributor to heart diseases in which ischemia and hypoxia are key elements, we tested the hypothesis that hypoxia predisposes neonatal rat ventricular myocytes (NRVM) to Fas-mediated apoptosis, by shifting the balance between antiapoptotic and proapoptotic proteins towards the latter. METHODS: Normoxic or hypoxic (22 h, 1% O(2)) cultured NRVM were exposed to recombinant Fas L (rFasL) for 7 h, and apoptosis measured thereafter. RESULTS: Whereas in normoxic NRVM, rFasL did not cause apoptosis measured by the TUNEL assay (4.8+/-0.5% in control versus 4.5+/-0.9% in rFasL), in hypoxic cultures rFasL increased the background apoptosis level by 100%. That Fas was functional in normoxic NRVM, despite its inability to mediate apoptosis, was evidenced by the finding that Fas activation increased the diastolic [Ca(2+)](i) levels measured by Fura 2 fluorescence, and caused arrhythmias. In support of our working hypothesis, hypoxia increased Fas expression by 200% (measured by quantitative Western blot), and the expression of the proapoptotic proteins ARTS and FADD by 323 and 250%, respectively, and decreased the expression of the antiapoptotic proteins ARC and FLIP by 90 and 60%, respectively. CONCLUSION: By upregulating Fas expression and key proapoptotic proteins, and by downregulating antiapoptotic proteins, hypoxia predisposes ventricular myocytes to Fas-induced apoptosis. 相似文献
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Martin Stroedicke Yacine Bounab Nadine Strempel Konrad Klockmeier Sargon Yigit Ralf P. Friedrich Gautam Chaurasia Shuang Li Franziska Hesse Sean-Patrick Riechers Jenny Russ Cecilia Nicoletti Annett Boeddrich Thomas Wiglenda Christian Haenig Sigrid Schnoegl David Fournier Rona K. Graham Michael R. Hayden Stephan Sigrist Gillian P. Bates Josef Priller Miguel A. Andrade-Navarro Matthias E. Futschik Erich E. Wanker 《Genome research》2015,25(5):701-713
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Angela M. Beattie RGN PhD Rona Campbell PhD Kavita Vedhara PhD 《Health expectations》2014,17(3):429-439
Objective Individuals who have had one diabetic foot ulcer (DFU) are at high risk for developing further DFUs. This study was designed to examine the emotional and behavioural consequences of living with this heightened risk of re‐ulceration. Participants and setting Fifteen women and men living in south‐west England were interviewed at home or at the university by an academic psychologist. Design Interviews were audiotaped and transcribed verbatim. Thematic analysis using the constant comparative method was employed for data analysis. Results Participants reported having little perceived control in preventing further DFUs. This lack of control was associated with a range of negative emotions including fears and worries about developing further foot ulcers, amputation and guilt for the past neglect. Tensions were present between participants’ beliefs and reported behaviours, that is, what they felt they ought to be doing and what they were actually doing to care for their feet; most engaged in ‘strategic adherence’, that is, conducting a trade‐off between living a normal life and following foot‐care advice. Conclusion A lack of perceived control appears central to the emotional and behavioural responses of individuals living with the threat of re‐ulceration. We propose that these responses may serve to increase individuals’ risk of re‐ulceration and that these ‘risk factors’ should be considered part of the management of this patient group. 相似文献
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Rona G. Giffard Alberto J.L. Macario Everly Conway de Macario 《The Journal of clinical investigation》2013,123(8):3206-3208
Protection of hair cells by HSP70 released by supporting cells is reported by May et al. in this issue of the JCI. Their findings suggest a new way to reduce ototoxicity from therapeutic medications and raise larger questions about the role and integration of heat shock proteins in non–cell-autonomous responses to stress. Increasing evidence suggests an important role for extracellular heat shock proteins in both the nervous system and the immune system. The work also suggests that defective chaperones could cause ear disease and supports the potential use of chaperone therapeutics. 相似文献