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排序方式: 共有3016条查询结果,搜索用时 15 毫秒
1.
Hui Yu Zhengming Chen Karla V. Ballman Mark A. Watson Ramaswamy Govindan Irena Lanc David G. Beer Raphael Bueno Lucian R. Chirieac Michael Herman Chui Guoan Chen Wilbur A. Franklin David R. Gandara Carlo Genova Kristine A. Brovsky Mary-Beth M. Joshi Daniel T. Merrick William G. Richards Fred R. Hirsch 《Journal of thoracic oncology》2019,14(1):25-36
Objectives
Anti–programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) immunotherapy has demonstrated success in the treatment of advanced NSCLC. Recently, PD-1/PD-L1 blockade also has demonstrated interesting results in small trials of neoadjuvant treatment in stage IB to IIIA NSCLC. In addition, several clinical trials using anti–PD-1/PD-L1 immunotherapy as an adjuvant or neoadjuvant treatment in patients with resectable stage NSCLC are ongoing. However, few analyses of anti–PD-1/PD-L1 immunotherapy–related biomarkers in early-stage squamous cell lung carcinoma (SqCLC) have been reported. In this study, we evaluated PD-L1 protein expression, tumor mutation burden, and expression of an immune gene signature in early-stage SqCLC, providing data for identifying the potential role for patients with anti–PD-1/PD-L1 treatment in early-stage SqCLC.Methods
A total of 255 specimens from patients with early-stage SqCLC were identified within participating centers of the Strategic Partnering to Evaluate Cancer Signatures program. PD-L1 protein expression by immunohistochemistry was evaluated by using the Dako PD-L1 22C3 pharmDx kit on the Dako Link 48 auto-stainer (Dako, Carpinteria, CA). Tumor mutation burden (TMB) was calculated on the basis of data from targeted genome sequencing. The T-effector and interferon gamma (IFN-γ) gene signature was determined from Affymetrix gene chip data (Affymetrix, Santa Clara, CA) from frozen specimens.Results
The prevalence of PD-L1 expression was 9.8% at a tumor proportion score cutoff of at least 50%. PD-L1 mRNA and programmed cell death 1 ligand 2 mRNA positively correlated with PD-L1 protein expression on tumor cells (TCs) and tumor-infiltrating immune cells. PD-L1 protein expression on tumor-infiltrating immune cells was correlated with the T-effector and IFN-γ gene signature (p < 0.001), but not with TMB. For TCs, all of these biomarkers were independent of each other and neither PD-L1 protein expression, TMB, or T-effector and IFN-γ gene signatures were independently prognostic for patient outcomes.Conclusions
Evaluation of PD-L1 expression, TMB, and T-effector and IFN-γ gene signatures in the cohort with early-stage SqCLC found them to be independent of each other, and none was associated with overall survival. Our results also support the hypothesis that PD-L1 expression is regulated by an intrinsic mechanism on TCs and an adaptive mechanism on immune cells. 相似文献2.
3.
Zinkevičienė Auksė Dumalakienė Irena Mieliauskaitė Diana Vilienė Rita Narkevičiūtė Ieva Girkontaitė Irutė 《Clinical rheumatology》2019,38(10):2803-2809
Clinical Rheumatology - Both Sjögren’s syndrome (SS) and non-autoimmune sicca syndrome (nSS) can show symptoms of dry eyes and a dry mouth, and objective reductions in tear and saliva... 相似文献
4.
De Baene Wouter Jansma Martijn J. Schouwenaars Irena T. Rutten Geert-Jan M. Sitskoorn Margriet M. 《Brain imaging and behavior》2020,14(6):2351-2366
Brain Imaging and Behavior - In healthy participants, the strength of task-evoked network reconfigurations is associated with cognitive performance across several cognitive domains. It is, however,... 相似文献
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David Jutri? Domagoj ?iki? Almo? Boro? Dyana Odeh Romana Gra?an An?elo Beleti? Irena Landeka Jur?evi? 《Arhiv za higijenu rada i toksikologiju》2023,74(3):218
Valproate is known to disturb the kidney function, and high doses or prolonged intake may cause serum ion imbalance, kidney tubular acidosis, proteinuria, hyperuricosuria, polyuria, polydipsia, and dehydration. The aim of this in vivo study was to see whether naringin would counter the adverse effects of high-dose valproate in C57Bl/6 mice and to which extent. As expected, valproate (150 mg/kg bw a day for 10 days) caused serum hyperkalaemia, more in male than female mice. Naringin reversed (25 mg/kg bw a day for 10 days) the hyperkalaemia and activated antioxidative defence mechanisms (mainly catalase and glutathione), again more efficiently in females. In males naringin combined with valproate was not as effective and even showed some prooxidative effects.KEY WORDS: calcium, catalase, hyperkalaemia, malondialdehyde, oxidative stress, potassium, sodium, superoxide dismutase 相似文献
8.
Mantani Polyxeni T. Dunér Pontus Ljungcrantz Irena Nilsson Jan Björkbacka Harry Fredrikson Gunilla Nordin 《BMC immunology》2019,20(1):1-17
The use of immunodeficient mice transplanted with human hematopoietic stem cells is an accepted approach to study human-specific infectious diseases such as HIV-1 and to investigate multiple aspects of human immune system development. However, mouse and human are different in sialylation patterns of proteins due to evolutionary mutations of the CMP-N-acetylneuraminic acid hydroxylase (CMAH) gene that prevent formation of N-glycolylneuraminic acid from N-acetylneuraminic acid. How changes in the mouse glycoproteins’ chemistry affect phenotype and function of transplanted human hematopoietic stem cells and mature human immune cells in the course of HIV-1 infection are not known. We mutated mouse CMAH in the NOD/scid-IL2Rγc−/− (NSG) mouse strain, which is widely used for the transplantation of human cells, using the CRISPR/Cas9 system. The new strain provides a better environment for human immune cells. Transplantation of human hematopoietic stem cells leads to broad B cells repertoire, higher sensitivity to HIV-1 infection, and enhanced proliferation of transplanted peripheral blood lymphocytes. The mice showed no effect on the clearance of human immunoglobulins and enhanced transduction efficiency of recombinant adeno-associated viral vector rAAV2/DJ8. NSG-cmah−/− mice expand the mouse models suitable for human cells transplantation, and this new model has advantages in generating a human B cell repertoire. This strain is suitable to study different aspects of the human immune system development, provide advantages in patient-derived tissue and cell transplantation, and could allow studies of viral vectors and infectious agents that are sensitive to human-like sialylation of mouse glycoproteins. 相似文献
9.
Małgorzata Kiełczykowska Ewelina Kopciał Joanna Kocot Jacek Kurzepa Zbigniew Marzec Irena Musik 《Pharmacological reports : PR》2018,70(6):1168-1172
Background
Selenium is an essential element which shows protective properties against diverse harmful factors. Lithium compounds are widely used in medicine, but, in spite of undoubted beneficial effects, treatment with these compounds may lead to severe side effects, including renal, gastrointestinal, neurological, endocrine and metabolic disorders. This study was aimed at evaluating the influence of selenium and/or lithium on lithium, iron, zinc and copper content in rats’ erythrocytes as well as estimate the action of additional selenium on lithium exposure effects.Methods
The experiment was performed on four groups of rats (six animals each): control – received saline; Li – received 2.7 mg Li/kg b.w. as lithium carbonate; Se – received 0.5 mg Se/kg b.w. as sodium selenite; Se + Li – received simultaneously 0.5 mg Se/kg b.w. and 2.7 mg Li/kg b.w. (sodium selenite and lithium carbonate). The administration was performed for three weeks, once a day by stomach tube, in form of water solutions. In erythrocytes the content of lithium, iron, zinc and copper was determined using flame atomic absorption spectroscopy.Results
Lithium treatment insignificantly disturbed iron and zinc homeostasis as well as markedly increased lithium accumulation and copper content in rat erythrocytes. Selenium coadministration reversed those effects.Conclusions
The beneficial effect of selenium on disturbances of studied microelements homeostasis as well as on preventing lithium accumulation in erythrocytes in Li receiving animals allows suggesting that further research on selenium application as an adjuvant in lithium therapy is worth carrying on. 相似文献10.
A method for the preservation of the olfactory nerve filaments in cases of hypertelorism correction is described. The cribriform plate is completely resected and the nerve filaments gathered in the midline after medial rotation of the orbits. In contrast to Converse's (1970) procedure of paramedian osteotomies the method allows full correction of all degrees of hypertelorism, even in the most extreme cases, without olfactory nerve impairment. 相似文献