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991.
992.
Paolo Tarantino 《Expert opinion on biological therapy》2019,19(5):383-385
In phase III ImPassion130 trial, the addition of immunotherapy to chemotherapy improved overall survival in metastatic triple-negative breast cancer patients. This benefit was significant only in patients harboring PD-L1-positive tumors, suggesting that stratification according to response biomarkers is needed to achieve consistent responses. Besides PD-L1 expression, a variety of potential biomarkers are under investigation for predicting immunotherapy efficacy in breast cancer, such as tumor-infiltrating lymphocytes, gene signatures, tumor mutational burden, microsatellite instability, and gut microbiome. Enriching future trials through these biomarkers could help identifying the population of responders, realizing what has been called precision immunotherapy. 相似文献
993.
Prandoni P 《Blood》2005,106(13):4027-4033
Venous thromboembolism (VTE) is a frequent complication in cancer patients and represents an important cause of morbidity and mortality. Especially in patients who have a poor life expectancy, preventing death from pulmonary embolism is the mainstay of treatment. Critically ill patients should promptly be administered thrombolytic drugs. Except for selected patients requiring aggressive therapy, the initial VTE treatment should be conducted with either adjusted-dose unfractionated heparin or fixed-dose low-molecular-weight heparin (LMWH). LMWHs have the potential to greatly simplify the initial treatment of VTE, making the treatment of suitable patients feasible in an outpatient setting. During anticoagulant therapy, cancer patients have a 2- to 4-fold higher risk of recurrent VTE and major bleeding complications when compared with noncancer patients. The long-term administration of LMWH should be considered as an alternative to anti-vitamin K drugs in patients with advanced disease and in those with conditions limiting the use of oral anticoagulants. Prolongation of anticoagulation should be considered for as long as the malignant disorder is active. The evidence of lowered cancer mortality in patients on LMWH has stimulated renewed interest in these agents as antineoplastic drugs and raises the distinct possibility that cancer and thrombosis share common mechanisms. 相似文献
994.
995.
Galbusera M Bresin E Noris M Gastoldi S Belotti D Capoferri C Daina E Perseghin P Scheiflinger F Fakhouri F Grünfeld JP Pogliani E Remuzzi G 《Blood》2005,106(3):925-928
Thrombotic thrombocytopenic purpura (TTP) is a rare disorder of small vessels that is associated with deficiency of the von Willebrand factor-cleaving protease, ADAMTS13. The presence of anti-ADAMTS13 autoantibodies is considered a factor predisposing to relapses. Despite close monitoring and intensive plasma treatment, in these patients acute episodes are still associated with substantial morbidity and mortality rates, and the optimal therapeutic option should be prevention of relapses. This study was conducted in a patient with recurrent TTP due to high titers of ADAMTS13 inhibitors, who used to have 2 relapses of TTP a year. The study compared the standard treatment plasma exchange with rituximab. Results documented that plasma exchange had only a small transient effect on ADAMTS13 activity and inhibitors; on the contrary, prophylaxis with rituximab was associated with disappearance of anti-ADAMTS13 antibodies, a progressive recovery of protease activity, and it allowed the patient to maintain a disease-free state during a more than 2-year follow-up. 相似文献
996.
Nag S Lamkhioued B Renzi PM 《American journal of respiratory and critical care medicine》2002,165(11):1540-1545
Previous studies have shown that the allergic late airway response (LR) is dependent on the leukotriene (LT) pathway in Brown Norway (BN) rats. In this same model, interleukin-2 (IL-2) has been shown to increase allergic airway responses without increasing LT production. This study examined the relationship between the upregulation of cellular immunity with IL-2 and the LT pathway in ovalbumin-sensitized BN rats. Airway responsiveness to LTD(4) was significantly increased in BN rats pretreated with IL-2 (20,000 U twice a day for 4.5 days). Treatment with montelukast, a cysteinyl LT(1) receptor antagonist, blocked IL-2's induced increase of the LR to ovalbumin challenge. When cytokine expression was assessed either by semiquantitative polymerase chain reaction or in situ hybridization, we found that montelukast decreased the amount of IL-4 mRNA expression in the lungs while increasing the amount of interferon-gamma mRNA expression 8 hours after challenge. These results indicate that upregulation of cellular immunity with IL-2 can increase the sensitivity of the airways to LTD(4) and that inhibition of the LT pathway will block the LR and modulate cytokine expression after antigen challenge. 相似文献
997.
Quality of life in dependent older adults living at home 总被引:10,自引:0,他引:10
Fassino S Leombruni P Abbate Daga G Brustolin A Rovera GG Fabris F 《Archives of gerontology and geriatrics》2002,35(1):9-20
The purpose of medical interventions today is to favor the duration of life and to assure its quality. For a proper evaluation of the quality of life (QoL) of the elderly, it is important to assess not only the health status, but also psychological, functional and existential domains. Up to now, QoL of the dependent older living at home does not seem to have received sufficient attention. This study is a population based, cross-sectional health survey, and tries to give a picture of the QoL conditions of a group of dependent elderly living at home, using a specifically designed structured interview. In addition to this interview the Activities of Daily Living (ADL) Index and the Zung rating scale for Anxiety and Depression (AD) were administered to a total of 167 elderly (60 males and 107 females). The most interesting results of the study are the following: (1) the definition of dependence is often worsen by cultural prejudices; (2) psychopathological factors show a deep negative effect on 'attitudes towards life' of the dependent elderly; (3) QoL of the dependent elderly people in this sample is mainly negatively influenced by the degree of depression. We believe that the 'QoL-oriented' therapeutic strategy should consider more articulated and multidisciplinary geriatric and psychosocial interventions in this population. 相似文献
998.
999.
An underestimated combination of opposites resulting in enhanced thrombotic tendency 总被引:4,自引:0,他引:4 下载免费PDF全文
Heterozygous carriers of factor V (FV) Leiden who also carry FV deficiency often develop venous thromboembolism, but the thrombosis risk associated with this rare condition (pseudohomozygous activated protein C resistance) is still unclear. The thrombosis risk of genetically characterized pseudohomozygotes (n = 6) was compared with that of FV Leiden heterozygotes (n = 683) and homozygotes (n = 50) recruited within a large cohort study on familial thrombophilia. Both thrombin generation and Kaplan-Meier thrombosis-free survival analyses were performed in different FV genotype groups. FV Leiden pseudohomozygotes showed significantly higher thrombosis risk than heterozygotes. The thrombin generation test in pseudohomozygotes showed a pattern similar to homozygotes. Accordingly, early thrombotic manifestations occurred in pseudohomozygotes at a similar rate as in homozygotes. Thus, failure to recognize FV deficiency in FV Leiden heterozygotes may result in an underestimate of the thrombosis risk and inadequate management of affected patients. 相似文献
1000.
A point mutation in the MET oncogene abrogates metastasis without affecting transformation 下载免费PDF全文
Silvia Giordano Alberto Bardelli Zhu Zhen Sylvie Menard Carola Ponzetto Paolo M. Comoglio 《Proceedings of the National Academy of Sciences of the United States of America》1997,94(25):13868-13872
The MET oncogene encodes the tyrosine kinase receptor for hepatocyte growth factor/scatter factor (HGF), known to stimulate invasive growth of epithelial cells. MET is overexpressed in a significant percentage of human cancers and is amplified during the transition between primary tumors and metastasis. To investigate whether this oncogene is directly responsible for the acquisition of the metastatic phenotype, we exploited a single-hit oncogenic version of MET, able to transform and to confer invasive and metastatic properties to nontumorigenic cells, both in vitro and in nude mice. We mutagenized the signal transducer docking site of Met (Y1349VHVX3Y1356VNV), which has the uncommon property of binding and activating multiple src homology region 2 (SH2)-containing intracellular effectors. Notably, a point mutation (H1351 → N) increased the transforming ability of the oncogene but abolished its metastatic potential. This mutation duplicates the Grb2 binding site, super-activating the Ras pathway and preventing the binding of the other intracellular transducers. Complementation in trans with another nonmetastatic mutant (N1358 → H), recruiting all the transducers downstream to Met except Grb2, rescued the invasive–metastatic phenotype. It is concluded that the metastatic potential of the MET oncogene relies on the properties of its multifunctional docking site, and that a single point mutation affecting signal transduction can dissociate neoplastic transformation from metastasis. 相似文献