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排序方式: 共有1519条查询结果,搜索用时 31 毫秒
1.
Emeline Colomba Patricia Pautier Fanny Pommeret Alexandra Leary 《Expert review of anticancer therapy》2019,19(6):437-446
Introduction: The landscape of poly (ADP-ribose) polymerase (PARP) inhibition in ovarian cancer is rapidly evolving and becoming increasingly complex. Ovarian cancer is leading therapeutic innovation by providing the proof of concept for DNA repair as a target. Three different PARP inhibitors have now received approvals in the US and Europe in different indications. Subtle but crucial differences can be found among the licensed indications for each PARP inhibitor in terms of histology, type of BRCA mutation (germline and/or somatic), number of prior lines of chemotherapy and whether the indication is in the treatment or maintenance settings.
Areas covered: We review the latest clinical data regarding the PARP inhibitor rucaparib in ovarian cancer, provide an update on the evolving landscape of PARP inhibition in ovarian cancer, and summarize avenues of ongoing and future research.
Expert opinion: All eligible patients should be offered a PARP inhibitor. SOLO1 trial results demonstrated an unprecedented benefit maintenance with PARP inhibitors in first line. Results from trials evaluating PARP inhibitors as maintenance in first line regardless of BRCA status and from trials evaluating combinatorial strategies are eagerly awaited. 相似文献
2.
John Hill Robert C. Stuart Hin K. Fung Enders K.W. Ng Fanny M. Cheung Sidney C.S. Chung C. Andrew van Hasselt 《The Laryngoscope》1997,107(10):1373-1377
The aim of this study was to investigate the origin of globus pharyngis with particular reference to esophageal disorders such as gastroesophageal reflux disease (GERD), motility disorders, structural abnormalities, other gastrointestinal tract diseases, and psychological profile. Previous studies on this subject using 24-hour pH monitoring give conflicting results and are hampered by the high background prevalence of asymptomatic GERD in the normal Western population. The local Chinese population is known to have a very low background level of GERD and therefore is an ideal study population. Twenty-six patients with globus pharyngis underwent 24-hour ambulatory pH monitoring, esophageal manometry, and esophagogas-troduodenoscopy with lower esophageal biopsy. A control group of 20 patients presenting with non-ulcer dyspepsia was similarly investigated. Personality profiles of the globus pharyngis subjects and an appropriate control group were assessed. Eight of the globus pharyngis group (30.7%) had evidence of GERD, whereas only one of the controls (5%) demonstrated GERD on 24-hour esophageal pH monitoring (P < 0.05). The manometric and personality profile studies did not show significant differences between study and control groups. We concluded that the finding of GERD in patients with globus pharyngis is not a coincidental finding but that there is a true association between GERD and globus pharyngis. 相似文献
3.
Transection of an optic nerve (ON) is followed by slow removal of myelin. We studied microglia for the expression of molecules that characterize activated myelin phagocytosing macrophages: MAC-1, FcγII/III receptor (FcR), MAC-2, and F4/80. In-vitro, microglia expressed all molecules and phagocytosed myelin. In-vivo, intact ON displayed high levels of MAC-1, little FcR and F4/80, and no MAC-2. The expression of these molecules was upregulated differentially in in-vivo degenerating ON: MAC-1 uniformly, FcR and F4/80 variably, and MAC-2 sporadically. The distribution of MAC-2 expression correlated best with a pattern of sporadic structural degeneration. Thus in-vivo, ON injury is followed by deficient microglia activation, which we suggest contributes significantly to the slow clearance of myelin. 相似文献
4.
5.
Upregulation of TGF-beta, FOXP3, and CD4+CD25+ regulatory T cells correlates with more rapid parasite growth in human malaria infection 总被引:8,自引:0,他引:8
Walther M Tongren JE Andrews L Korbel D King E Fletcher H Andersen RF Bejon P Thompson F Dunachie SJ Edele F de Souza JB Sinden RE Gilbert SC Riley EM Hill AV 《Immunity》2005,23(3):287-296
Understanding the regulation of immune responses is central for control of autoimmune and infectious disease. In murine models of autoimmunity and chronic inflammatory disease, potent regulatory T lymphocytes have recently been characterized. Despite an explosion of interest in these cells, their relevance to human disease has been uncertain. In a longitudinal study of malaria sporozoite infection via the natural route, we provide evidence that regulatory T cells have modifying effects on blood-stage infection in vivo in humans. Cells with the characteristics of regulatory T cells are rapidly induced following blood-stage infection and are associated with a burst of TGF-beta production, decreased proinflammatory cytokine production, and decreased antigen-specific immune responses. Both the production of TGF-beta and the presence of CD4+CD25+FOXP3+ regulatory T cells are associated with higher rates of parasite growth in vivo. P. falciparum-mediated induction of regulatory T cells may represent a parasite-specific virulence factor. 相似文献
6.
7.
Moyle GJ Daar ES Gertner JM Kotler DP Melchior JC O'brien F Svanberg E;Serono Study Team 《Journal of acquired immune deficiency syndromes (1999)》2004,35(4):367-375
HIV-associated wasting is defined as > or = 10% involuntary weight loss and includes declines in both lean and fat mass. This large (757 subjects), randomized, double-blind, placebo-controlled trial investigated the efficacy, safety, and tolerability of recombinant human growth hormone (rhGH) in 2 doses-0.1 mg/kg up to a maximum of 6 mg daily (DD) or alternate days (AD)-in the treatment of wasting and weight loss in highly active antiretroviral therapy (HAART)-treated HIV-infected subjects. The evaluable population for ergometry comprised 555 subjects, 87.6% of whom were receiving HAART. At 12 weeks, median maximum work output increased by 2.4 and 2.6 kJ in the AD and DD groups, respectively. The median treatment difference was 2.9 kJ for DD vs. placebo (P < 0.0001). Body weight increased by 2.2 and 2.9 kg in the AD and DD groups, respectively. Corresponding median treatment differences vs. placebo were 1.5 and 2.2 kg (P < 0.0001). Lean body mass (LBM), by bioelectric impedance spectroscopy, increased by 3.3 and 5.2 kg, respectively (P < 0.0001 vs. placebo; P = 0.0173 DD vs. AD), and fat mass, predominately truncal, decreased. Quality of life (QoL) improved significantly in both rhGH groups. Fluid-retention adverse effects and hyperglycemia were more common in the DD than in the AD group. No significant changes in HIV viral load or CD4 cell count occurred. In conclusion, over the 12-week course of therapy, rhGH, 0.1 mg/kg DD, was superior to placebo in improving physical function, body weight, body composition, and QoL and was superior to AD dosing in restoring LBM. 相似文献
8.
Transient requirement of the PrrA-PrrB two-component system for early intracellular multiplication of Mycobacterium tuberculosis 总被引:1,自引:0,他引:1
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Ewann F Jackson M Pethe K Cooper A Mielcarek N Ensergueix D Gicquel B Locht C Supply P 《Infection and immunity》2002,70(5):2256-2263
Adaptive regulation of gene expression in response to environmental changes is a general property of bacterial pathogens. By screening an ordered transposon mutagenesis library of Mycobacterium tuberculosis, we have identified three mutants containing a transposon in the coding sequence or in the 5' regions of genes coding for two-component signal transduction systems (trcS, regX3, prrA). The intracellular multiplication capacity of the three mutants was investigated in mouse bone marrow-derived macrophages. Only the prrA mutant showed a defect in intracellular growth during the early phase of infection, and this defect was fully reverted when the mutant was complemented with prrA-prrB wild-type copies. The mutant phenotype was transient, as after 1 week this strain recovered full growth capacity to reach levels similar to that of the wild type at day 9. Moreover, a transient induction of prrA promoter activity was observed during the initial phase of macrophage infection, as shown by a prrA promoter-gfp fusion in M. bovis BCG infecting the mouse macrophages. The concordant transience of the prrA mutant phenotype and prrA promoter activity indicates that the PrrA-PrrB two-component system is involved in the environmental adaptation of M. tuberculosis, specifically in an early phase of the intracellular growth, and that, similar to other facultative intracellular parasites, M. tuberculosis can use genes temporarily required at different stages in the course of macrophage infection. 相似文献
9.
Camille Granger Paul Guedeney Camille Arnaud Soulef Guendouz Claire Cimadevilla Mathieu Kerneis Caroline Kerneis Michel Zeitouni Constance Verdonk Camille Legeai Guillaume Lebreton Pascal Leprince Eva Désiré Sabato Sorrentino Johanne Silvain Gilles Montalescot Fanny Hazan Shaida Varnous Richard Dorent 《Transplant international》2021,34(4):721-731
Available data on clinical presentation and mortality of coronavirus disease-2019 (COVID-19) in heart transplant (HT) recipients remain limited. We report a case series of laboratory-confirmed COVID-19 in 39 HT recipients from 3 French heart transplant centres (mean age 54.4 ± 14.8 years; 66.7% males). Hospital admission was required for 35 (89.7%) cases including 14/39 (35.9%) cases being admitted in intensive care unit. Immunosuppressive medications were reduced or discontinued in 74.4% of the patients. After a median follow-up of 54 (19–80) days, death and death or need for mechanical ventilation occurred in 25.6% and 33.3% of patients, respectively. Elevated C-reactive protein and lung involvement ≥50% on chest computed tomography (CT) at admission were associated with an increased risk of death or need for mechanical ventilation. Mortality rate from March to June in the entire 3-centre HT recipient cohort was 56% higher in 2020 compared to the time-matched 2019 cohort (2% vs. 1.28%, P = 0.15). In a meta-analysis including 4 studies, pre-existing diabetes mellitus (OR 3.60, 95% CI 1.43–9.06, I2 = 0%, P = 0.006) and chronic kidney disease stage III or higher (OR 3.79, 95% CI 1.39–10.31, I2 = 0%, P = 0.009) were associated with increased mortality. These findings highlight the aggressive clinical course of COVID-19 in HT recipients. 相似文献
10.
目的:对一叶萩枝叶的化学成分进行研究。方法:应用各种色谱技术从一叶萩总碱部位中分离化合物,根据理化常数和波谱(NMR及MS等)分析方法对化合物的结构进行鉴定。结果:自一叶萩枝叶的总碱部位中分离得到11个化合物。分别鉴定为:(-)-15β-ethoxy-14,15-dihvdroviroallosecurinine(1),一叶萩碱(securinine,2),二氢一叶萩碱(14,15-dihydrosecurinine,3),4-epiph),llanthine(4),securitinine(5),右旋别一叶萩碱(viroallosecurinine,6),一叶萩醇A(securinol A,7),secu’amamineA(8),ent-phyllanthidine(9),(+)-aquilegiohde(10)和(+)-menisdaurilide(11)。结论:1为新化合物,4,8,10和11为首次从一叶萩中分离得到。 相似文献