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Risk of hepatitis B virus reactivation in oncological patients treated with tyrosine kinase inhibitors:A case report and literature analysis 被引量:4
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作者 Francesca Colapietro Nicola Pugliese +2 位作者 Antonio Voza Alessio Aghemo Stella De Nicola 《World Journal of Gastroenterology》 SCIE CAS 2024年第9期1253-1256,共4页
Hepatitis B virus(HBV)reactivation(HBVr)represents a severe and potentially life-threatening condition,and preventive measures are available through blood test screening or prophylactic therapy administration.The asse... Hepatitis B virus(HBV)reactivation(HBVr)represents a severe and potentially life-threatening condition,and preventive measures are available through blood test screening or prophylactic therapy administration.The assessment of HBVr traditionally considers factors such as HBV profile,including hepatitis B surface antigen(HBsAg)and antibody to hepatitis B core antigen,along with type of medication(chemotherapy;immunomodulants).Nevertheless,consideration of possible patient’s underlying tumor and the specific malignancy type(solid or hematologic)plays a crucial role and needs to be assessed for decision-making process. 展开更多
关键词 Chronic hepatitis B REACTIVATION Nucleoside analogue tyrosine kinase inhibitors Onco-hematology
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Advances in MET tyrosine kinase inhibitors in gastric cancer
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作者 Yifan Zhang Lin Shen Zhi Peng 《Cancer Biology & Medicine》 SCIE CAS CSCD 2024年第6期484-498,共15页
Gastric cancer is among the most frequently occurring cancers and a leading cause of cancer-related deaths globally.Because gastric cancer is highly heterogenous and comprised of different subtypes with distinct molec... Gastric cancer is among the most frequently occurring cancers and a leading cause of cancer-related deaths globally.Because gastric cancer is highly heterogenous and comprised of different subtypes with distinct molecular and clinical characteristics,the management of gastric cancer calls for better-defined,biomarker-guided,molecular-based treatment strategies.MET is a receptor tyrosine kinase mediating important physiologic processes,such as embryogenesis,tissue regeneration,and wound healing.However,mounting evidence suggests that aberrant MET pathway activation contributes to tumour proliferation and metastasis in multiple cancer types,including gastric cancer,and is associated with poor patient outcomes.As such,MET-targeting therapies are being actively developed and promising progress has been demonstrated,especially with MET tyrosine kinase inhibitors.This review aims to briefly introduce the role of MET alterations in gastric cancer and summarize in detail the current progress of MET tyrosine kinase inhibitors in this disease area with a focus on savolitinib,tepotinib,capmatinib,and crizotinib.Building on current knowledge,this review further discusses existing challenges in MET alterations testing,possible resistance mechanisms to MET inhibitors,and future directions of MET-targeting therapies. 展开更多
关键词 Gastric cancer MET alterations MET tyrosine kinase inhibitors savolitinib MET testing
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Navigating the complex terrain of hepatitis B virus reactivation in the era of Bruton tyrosine kinase inhibitors
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作者 Wei-Nung Liu Ming-Shen Dai +1 位作者 Felicia Lin Gen-Min Lin 《World Journal of Gastroenterology》 SCIE CAS 2024年第21期2748-2750,共3页
In this editorial,we offer a summary of the risk associated with hepatitis B reactivation(HBVr)in the setting of both solid and hematologic malignancies treated with Bruton tyrosine kinase(BTK)inhibitors,with insights... In this editorial,we offer a summary of the risk associated with hepatitis B reactivation(HBVr)in the setting of both solid and hematologic malignancies treated with Bruton tyrosine kinase(BTK)inhibitors,with insights derived from current studies.Furthermore,we emphasize the critical need for a framework regarding robust risk evaluation in patients undergoing such treatments.This framework is essential for identifying those at increased risk of HBVr,enabling healthcare providers to implement proactive measures to prevent reactivation and ensure the safe administration of BTK inhibitor therapy. 展开更多
关键词 Hepatitis B virus reactivation Bruton tyrosine kinase inhibitors Hematologic malignancies Solid tumors Prophylaxis guidelines
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MicroRNA-298 determines the radio-resistance of colorectal cancer cells by directly targeting human dual-specificity tyrosine(Y)-regulated kinase 1A
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作者 Mei-Zhu Shen Yong Zhang +6 位作者 Fang Wu Mei-Zhen Shen Jun-Lin Liang Xiao-Long Zhang Xiao-Jian Liu Xin-Shu Li Ren-Sheng Wang 《World Journal of Gastrointestinal Oncology》 SCIE 2024年第4期1453-1464,共12页
BACKGROUND Radiotherapy stands as a promising therapeutic modality for colorectal cancer(CRC);yet,the formidable challenge posed by radio-resistance significantly undermines its efficacy in achieving CRC remission.AIM... BACKGROUND Radiotherapy stands as a promising therapeutic modality for colorectal cancer(CRC);yet,the formidable challenge posed by radio-resistance significantly undermines its efficacy in achieving CRC remission.AIM To elucidate the role played by microRNA-298(miR-298)in CRC radio-resistance.METHODS To establish a radio-resistant CRC cell line,HT-29 cells underwent exposure to 5 gray ionizing radiation that was followed by a 7-d recovery period.The quantification of miR-298 levels within CRC cells was conducted through quantitative RT-PCR,and protein expression determination was realized through Western blotting.Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and proliferation by clonogenic assay.Radio-induced apoptosis was discerned through flow cytometry analysis.RESULTS We observed a marked upregulation of miR-298 in radio-resistant CRC cells.MiR-298 emerged as a key determinant of cell survival following radiation exposure,as its overexpression led to a notable reduction in radiation-induced apoptosis.Intriguingly,miR-298 expression exhibited a strong correlation with CRC cell viability.Further investigation unveiled human dual-specificity tyrosine(Y)-regulated kinase 1A(DYRK1A)as miR-298’s direct target.CONCLUSION Taken together,our findings underline the role played by miR-298 in bolstering radio-resistance in CRC cells by means of DYRK1A downregulation,thereby positioning miR-298 as a promising candidate for mitigating radioresistance in CRC. 展开更多
关键词 MicroRNA-298 Human dual-specificity tyrosine(Y)-regulated kinase 1A Colorectal cancer Radio-resistance p53 binding protein 1
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Advanced Lung Adenocarcinoma with EGFR 19-del Mutation Transformed into SCC after EGFR-tyrosine Kinase inhibitors Treatment:A Case report
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作者 Xing-Zu Ji Zhong-Da Liu +4 位作者 Yi-Ping Ye Quan Li Xiao-Jing Liu Min-Hua Zhou Yi Jin 《World Journal of Clinical Cases》 SCIE 2024年第20期4405-4411,共7页
BACKGROUND Epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs)significantly improve the survival of patients with Epidermal growth factor receptor(EGFR)sensitive mutations in non-small cell lung can... BACKGROUND Epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs)significantly improve the survival of patients with Epidermal growth factor receptor(EGFR)sensitive mutations in non-small cell lung cancer(NSCLC).CASE SUMMARY A 67-year-old female patient in advanced lung adenocarcinoma suffered from drug resistance after EGFR-TKIs treatment.Secondary pathological tissue biopsy confirmed squamous cell carcinoma(SCC)transformation.Patients inevitably encountered drug resistance issues after receiving EGFR-TKIs treatment for a certain period of time,while EGFR-TKIs can significantly improve the survival of patients with EGFR-sensitive mutations in NSCLC.Notably,EGFR-TKIs resistance includes primary and acquired.Pathological transformation is one of the mechanisms of acquired resistance in EGFR-TKIs,with SCC transformation being relatively rare.Our results provide more detailed results of the patient’s diagnosis and treatment process on SCC transformation after EGFR-TKIs treatment for lung adenocarcinoma.CONCLUSION Squamous cell carcinoma transformation is one of the acquired resistance mechanisms of EGFR-TKIs in advanced lung adenocarcinoma with EGFR mutations. 展开更多
关键词 Lung adenocarcinoma Squamous cell carcinoma Pathological histological transformation Epidermal growth factor receptor tyrosine kinase inhibitors Drug resistance Case report
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Bruton’s tyrosine kinase inhibitors in primary central nervous system lymphoma:New hopes on the horizon
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作者 Leonardo S Lino-Silva Sabrina B Martínez-Villavicencio Luisa Fernanda Rivera-Moncada 《World Journal of Clinical Oncology》 2024年第5期587-590,共4页
In this editorial,we comment on the article by Wang et al.This manuscript explores the potential synergistic effects of combining zanubrutinib,a novel oral inhibitor of Bruton’s tyrosine kinase,with high-dose methotr... In this editorial,we comment on the article by Wang et al.This manuscript explores the potential synergistic effects of combining zanubrutinib,a novel oral inhibitor of Bruton’s tyrosine kinase,with high-dose methotrexate(HD-MTX)as a therapeutic intervention for primary central nervous system lymphoma(PCNSL).The study involves a retrospective analysis of 19 PCNSL patients,highlighting clinicopathological characteristics,treatment outcomes,and genomic biomarkers.The results indicate the combination’s good tolerance and strong antitumor activity,with an 84.2%overall response rate.The authors emphasize the potential of zanubrutinib to modulate key genomic features of PCNSL,particularly mutations in myeloid differentiation primary response 88 and cluster of differentiation 79B.Furthermore,the study investigates the role of circulating tumor DNA in cerebrospinal fluid for disease surveillance and treatment response monitoring.In essence,the study provides valuable insights into the potential of combining zanubrutinib with HD-MTX as a frontline therapeutic regimen for PCNSL.The findings underscore the importance of exploring alternative treatment modalities and monitoring genomic and liquid biopsy markers to optimize patient outcomes.While the findings suggest promise,the study’s limitations should be considered,and further research is needed to establish the clinical relevance of this therapeutic approach for PCNSL. 展开更多
关键词 Primary central nervous system lymphoma Zanubrutinib Bruton’s tyrosine kinase PROGNOSIS Myeloid differentiation primary response 88 gene Cluster of differentiation 79B gene
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N-methyl-D-aspartate receptors mediate diphosphorylation of extracellular signal-regulated kinases through Src family tyrosine kinases and Ca^2+/calmodulin-dependent protein kinase Ⅱ in rat hippocampus after cerebral ischemia 被引量:7
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作者 吴辉文 李洪福 郭军 《Neuroscience Bulletin》 SCIE CAS CSCD 2007年第2期107-112,共6页
Objective: Extracellular signal-regulated kinases (ERKs) can be activated by calcium signals. In this study, we investigated whether calcium-dependent kinases were involved in ERKs cascade activation after global c... Objective: Extracellular signal-regulated kinases (ERKs) can be activated by calcium signals. In this study, we investigated whether calcium-dependent kinases were involved in ERKs cascade activation after global cerebral ischemia. Methods Cerebral ischemia was induced by four-vessel occlusion, and the calcium-dependent proteins were detected by immunoblot. Results Lethal-simulated ischemia significantly resulted in ERKs activation in N-methyl-D-aspartate (NMDA) receptor-dependent manner, accompanying with differential upregulation of Src kinase and Ca^2+/calmodulin-dependent protein kinase Ⅱ (CaMKⅡ) activities. With the inhibition of Src family tyrosine kinases or CaMKⅡ by administration of PP2 or KN62, the phosphorylation of ERKs was impaired dramatically during post-ischemia recovery. However, ischemic challenge also repressed ERKs activity when Src kinase was excessively activated. Conclusions Src family tyrosine kinases and CaMKⅡ might be involved in the activation of ERKs mediated by NMDA receptor in response to acute ischemic stimuli in vivo, but the intense activation of Src kinase resulted from ischemia may play a reverse role in the ERKs cascade. 展开更多
关键词 cerebral ischemia extracellular signal-regulated kinases NMDA receptors Src family tyrosine kinases CaMKⅡ
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Effect of a novel tyrosine kinase inhibitor nintedanib on bFGF and VEGF concentrations in a rabbit retinal vein occlusion model
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作者 Wei Fang Jing Zhai +3 位作者 Zhen-Bin Qian Hai-Dong Li Meng-Di Wang Li-Jun Shen 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2023年第9期1450-1455,共6页
AIM:To evaluate whether a novel tyrosine kinase inhibitor nintedanib could inhibit basic fibroblast growth factor(bFGF)and vascular endothelial growth factor(VEGF)simultaneously for retinal vascular disease in vivo.ME... AIM:To evaluate whether a novel tyrosine kinase inhibitor nintedanib could inhibit basic fibroblast growth factor(bFGF)and vascular endothelial growth factor(VEGF)simultaneously for retinal vascular disease in vivo.METHODS:After a laser induced rabbit retinal vein occlusion(RVO)model was made,0.5 mg of nintedanib was injected intravitreally in the left eye on the third day while the right eye was as a control.Intracameral samples were taken on the day before laser treatment and days 1,3,7,14,21,and 28 after treatment.Enzyme-linked immunosorbent assay(ELISA)was used to test the bFGF and VEGF-A concentrations in the aqueous humor.RESULTS:Both bFGF and VEGF-A rose significantly on the third day after laser treatment in both eyes.In the control eye the bFGF concentration peaked on the 14th day while the VEGF-A concentration dropped rapidly soon after the third day.After nintadanib injection in the study eye,both bFGF and VEGF-A showed a significant reduction on the 4th day(7th day after laser treatment)when compared to the control eye,and kept on low level in the following several weeks.CONCLUSION:Intravitreal injection of nintedanib can inhibit the expression of bFGF and VEGF in the process of RVO model to a certain extent,which is expected to become a new method for the treatment of retinal vascular diseases or fibrotic diseases. 展开更多
关键词 retinal vein occlusion nintedanib tyrosine kinase inhibitor basic fibroblast growth factor vascular endothelial growth factor rabbit model
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Tyrosine kinase inhibitors and human epidermal growth factor receptor-2 positive breast cancer
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作者 Aya Abunada Zaid Sirhan +1 位作者 Anita Thyagarajan Ravi P Sahu 《World Journal of Clinical Oncology》 CAS 2023年第5期198-202,共5页
The body of evidence investigating human epidermal growth factor receptor-2(HER2)directed therapy in patients with breast cancer(BC)has been growing within the last decade.Recently,the use of tyrosine kinase inhibitor... The body of evidence investigating human epidermal growth factor receptor-2(HER2)directed therapy in patients with breast cancer(BC)has been growing within the last decade.Recently,the use of tyrosine kinase inhibitors(TKIs)has been of particular interest in the treatment of human malignancies.This literature commentary is intended to highlight the most recent findings associated with the widely-studied TKI agents and their clinical significance in improving the outcomes of HER2 positive BC. 展开更多
关键词 Human epidermal growth factor receptor-2 positive breast cancer tyrosine kinase inhibitors LAPATINIB Pyrotinib Tucatinib TRASTUZUMAB
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Rituximab combined with Bruton tyrosine kinase inhibitor to treat elderly diffuse large B-cell lymphoma patients: Two case reports
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作者 Cang-Jian Zhang Min-Lei Zhao 《World Journal of Clinical Cases》 SCIE 2023年第29期7170-7178,共9页
BACKGROUND Diffuse large B-cell lymphoma(DLBCL)is a common aggressive non-Hodgkin's lymphoma(NHL),accounting for 30%-40%of adult NHLs.This report aims to explore the efficacy and safety of rituximab combined with ... BACKGROUND Diffuse large B-cell lymphoma(DLBCL)is a common aggressive non-Hodgkin's lymphoma(NHL),accounting for 30%-40%of adult NHLs.This report aims to explore the efficacy and safety of rituximab combined with Bruton tyrosine kinase inhibitors(BTKis)in the treatment of elderly patients with DLBCL.CASE SUMMARY The clinical data of two elderly patients with DLBCL who received rituximab combined with BTKi in our hospital were retrospectively analyzed,and the literature was reviewed.The patients were treated with chemotherapy using the R-miniCHOP regimen for two courses.Then,they received rituximab in combination with BTKi.CONCLUSION The treatment experience in these cases demonstrates the potential efficacy of rituximab combined with BTKi to treat elderly DLBCL patients,thus providing a new treatment strategy. 展开更多
关键词 Diffuse large B-cell lymphoma RITUXIMAB Bruton tyrosine kinase inhibitors Elderly patients Case report
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Targeting receptor tyrosine kinases in gastric cancer 被引量:5
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作者 Asahiro Morishita Jian Gong Tsutomu Masaki 《World Journal of Gastroenterology》 SCIE CAS 2014年第16期4536-4545,共10页
Molecularly targeted therapeutic agents are constantly being developed and have been shown to be effective in various clinical trials. One group of representative targeted oncogenic kinases, the receptor tyrosine kina... Molecularly targeted therapeutic agents are constantly being developed and have been shown to be effective in various clinical trials. One group of representative targeted oncogenic kinases, the receptor tyrosine kinases (RTKs), has been associated with gastric cancer development. Trastuzumab, an inhibitor of ERBB2, has been approved for the treatment of gastric cancer, although other receptor tyrosine kinases, such as epidermal growth factor receptor, vascular endothelial growth factor, platelet-derived growth factor receptor, c-Met, IGF-1R and fibroblast growth factor receptor 2, are also activated in gastric cancer. The promising results of the trastuzumab clinical trial for gastric cancer resulted in the approval of trastuzumab-based therapy as a first-line treatment for human epidermal growth factor receptor 2-positive patients. On the other hand, the trial examining bevacizumab in combination with conventional chemotherapy did not meet its primary goal of increasing the overall survival time of gastric cancer patients; however, a significantly higher response rate and a longer progression-free survival were observed in the bevacizumab arm of the trial. Other clinical trials, especially phase III trials that have tested drugs targeting RTKs, such as cetuximab, panitumumab, gefitinib, erlotinib, figitumumab, sorafenib, sunitinib and lapatinib, have shown that these drugs have modest effects against gastric cancer. This review summarizes the recent results from the clinical trials of molecularly targeted drugs and suggests that further improvements in the treatment of advanced gastric cancer can be achieved through the combination of conventional drugs with the new molecularly targeted therapies. 展开更多
关键词 Receptor tyrosine kinases Gastric cancer Epidermal growth factor receptor TRASTUZUMAB CETUXIMAB LAPATINIB PANITUMUMAB ERLOTINIB Bevacizumab
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Negative regulation of receptor tyrosine kinases: unexpected links to c-Cbl and receptorubiquitylation 被引量:5
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作者 Chanan RUBIN Gal GUR Yosef YARDEN 《Cell Research》 SCIE CAS CSCD 2005年第1期66-71,共6页
Intracellular signals mediated by the family of receptor tyrosine kinases play pivotal roles in morphogenesis, cell fate determination and pathogenesis. Precise control of signal amplitude and duration is critical for... Intracellular signals mediated by the family of receptor tyrosine kinases play pivotal roles in morphogenesis, cell fate determination and pathogenesis. Precise control of signal amplitude and duration is critical for the fidelity and robustness of these processes. Activation of receptor tyrosine kinases by their cognate growth factors not only leads to propagation of the signal through various biochemical cascades, but also sets in motion multiple attenuation mechanisms that ulti- mately terminate the active state. Early attenuators pre-exist prior to receptor activation and they act to limit signal propagation. Subsequently, late attenuators, such as Lrig and Sprouty, are transcriptionally induced and further act to dampen the signal. Central to the process of signaling attenuation is the role of the E3 ubiquitin ligase c-Cbl. While Cbl- mediated processes of receptor ubiquitylation and endocytosis are relatively well understood, the links of Cbl to other negative regulators are just now beginning to be appreciated. Here we review some emerging interfaces between Cbl and the transcriptionally induced negative regulators Lrig and Sprouty. 展开更多
关键词 ENDOCYTOSIS growth factor ONCOGENE signal transduction UBIQUITIN tyrosine kinase.
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Advances in nanotechnology-based delivery systems for EGFR tyrosine kinases inhibitors in cancer therapy 被引量:1
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作者 Xiaohan Zhou Kun Shi +4 位作者 Ying Hao Chengli Yang Ruoyu Zha Cheng Yi Zhiyong Qian 《Asian Journal of Pharmaceutical Sciences》 SCIE CAS 2020年第1期26-41,共16页
Oral tyrosine kinase inhibitors(TKIs) against epidermal growth factor receptor(EGFR) family have been introduced into the clinic to treat human malignancies for decades. Despite superior properties of EGFR-TKIs as sma... Oral tyrosine kinase inhibitors(TKIs) against epidermal growth factor receptor(EGFR) family have been introduced into the clinic to treat human malignancies for decades. Despite superior properties of EGFR-TKIs as small molecule targeted drugs, their applications are still restricted due to their low solubility, capricious oral bioavailability, large requirement of daily dose, high binding tendency to plasma albumin and initial/acquired drug resistance. Nanotechnology is a promising tool to improve efficacy of these drugs. Through non-oral routes. Various nanotechnology-based delivery approaches have been developed for providing efficient delivery of EGFR-TKIs with a better pharmacokinetic profile and tissue-targeting ability. This review aims to indicate the advantage of nanocarriers for EGFR-TKIs delivery. 展开更多
关键词 NANOTECHNOLOGY EGFR tyrosine kinasE INHIBITOR Cancer therapy
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ABNORMAL PROTEIN TYROSINE KINASES ASSOCIATED WITH HUMAN HAEMATOLOGICAL MALIGNANCIES
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作者 孙雪梅 Graham J Lieschke 《Chinese Journal of Cancer Research》 SCIE CAS CSCD 2002年第2期79-83,共5页
Objective: To survey the role of protein tyrosine kinases (PTKs) in the pathogenesis of several hematopoietic malignancies. Methods: By reviewing the published laboratory and clinical studies on PTK-related oncoprotei... Objective: To survey the role of protein tyrosine kinases (PTKs) in the pathogenesis of several hematopoietic malignancies. Methods: By reviewing the published laboratory and clinical studies on PTK-related oncoproteins and their causative role in some leukemias and lymphomas. Results: Protein tyrosine kinases are key participants in signal transduction pathways that regulate cellular growth, activation and differentiations. Aberrant PTK activity resulting from gene mutation (often accompanying chromosome translocation) plays an etiologic role in several clonal hematopoietic malignancies. For example, the PTK product of the BCR-ABL fusion gene resulting from the t (9; 22) translocation exhibits several fold higher tyrosine kinase activity than the product of the ABL gene. Evidence suggests that the BCR-ABL oncoprotein alone is sufficient to case chronic myelogenous leukemia (CML) and other Ph positive acute leukemia. PTK over-activity resulting from chromosomal translocations creating TEL-ABL, TEL-JAK2 and TEL-PDGFRβ fusion proteins plays an important role in the pathogenesis of other types of leukemia. Another example occurs in anaplastic large cell lymphoma (ALCL). Experimental and clinical evidences indicate that translocations involving ALK gene on chromosome 2p23, most commonly resulting in an NPM-ALK fusion oncogene, result in constitutive activation of ALK and cause ALCL. This group of lymphomas is now named ALK positive lymphoma or ALKoma. Conclusion: Genetic lesions creating aberrant fusion proteins that result in excessive PTK activity are increasingly being recognized as central to the pathogenesis of hemotopoietic malignancies. These chimeric PTK molecules represent attractive disease-specific targets against which new classes therapeutic agents are being developed. 展开更多
关键词 Protein tyrosine kinase (PTK) Hematopoietic malignancy BCR-ABL Chronic myelogenous leukemia (CML) Anaplastic large cell lymphoma (ALCL) STI 571 Protein tyrosine kinase inhibitor
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bFGF激活tyrosine kinase/PI3K/PLCγ增加血管内皮细胞[Mg^2+]i的研究 被引量:3
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作者 洪炳哲 王丽萍 +5 位作者 高立建 谢同杰 朴海南 李婉秋 刘学田 李胜范 《中国药理学通报》 CAS CSCD 北大核心 2008年第1期50-53,共4页
目的探讨碱性成纤维细胞生长因子(basic fibroblastgrowth factor,bFGF)对人脐带静脉内皮细胞(human umbilicalvein endothelial cells,HUVECs)内游离镁离子浓度([Mg2+]i)的调节机制研究。方法我们采用荧光指示剂mag-fura-2,运用PTi阳... 目的探讨碱性成纤维细胞生长因子(basic fibroblastgrowth factor,bFGF)对人脐带静脉内皮细胞(human umbilicalvein endothelial cells,HUVECs)内游离镁离子浓度([Mg2+]i)的调节机制研究。方法我们采用荧光指示剂mag-fura-2,运用PTi阳离子测定系统动态测HUVECs的[Mg2+]i。结果经酪氨酸激酶阻断剂(tyrphostin A23和genistein)、3-磷脂酰肌醇激酶阻断剂(wortmannin和LY294002)、磷脂酶Cγ阻断剂(U73122)预处理,能阻断bF-GF诱导的[Mg2+]i增加。但经磷脂酶Cγ阻断剂无活性的类似物(U73343)和丝裂原活化蛋白激酶阻断剂(SB202190和PD98059)预处理,不能阻断bFGF诱导的[Mg2+]i增加。结论bFGF通过酪氨酸激酶/3-磷脂酰肌醇激酶/磷脂酶Cγ信号传递途径使细胞内的Mg2+库释放Mg2+,从而增加HUVECs的[Mg2+]i。 展开更多
关键词 碱性成纤维细胞生长因子 酪氨酸激酶 3-磷脂酰肌醇激酶 磷脂酶Cγ
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血管生成素-1激活tyrosine kinase/PI3K增加血管内皮细胞[Mg^2+]i 被引量:3
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作者 谢同杰 洪炳哲 +5 位作者 李胜范 王丽萍 朴海南 高立建 刘学田 陈毓婷 《中国病理生理杂志》 CAS CSCD 北大核心 2008年第9期1665-1669,共5页
目的:探讨血管生成素-1(Ang-1)对人脐静脉内皮细胞(HUVECs)内游离镁离子浓度([Mg2+]i)的调节机制。方法:我们采用荧光指示剂mag-fura-2,运用PTi阳离子测定系统动态测HUVECs的[Mg2+]i。结果:Ang-1诱导的[Mg2+]i增加与细胞外Mg2+浓度无关... 目的:探讨血管生成素-1(Ang-1)对人脐静脉内皮细胞(HUVECs)内游离镁离子浓度([Mg2+]i)的调节机制。方法:我们采用荧光指示剂mag-fura-2,运用PTi阳离子测定系统动态测HUVECs的[Mg2+]i。结果:Ang-1诱导的[Mg2+]i增加与细胞外Mg2+浓度无关。Ang-1诱导的[Mg2+]i增加与细胞内Ca2+浓度无关。经酪氨酸激酶阻断剂(tyrphostin A23和genistein),磷脂酰3激酶阻断剂(wortmannin和LY294002)预处理,均显著阻断Ang-1诱导的[Mg2+]i增加。但经活化丝裂原激活激酶阻断剂(SB202190和PD98059)预处理,不能阻断Ang-1诱导的[Mg2+]i增加。结论:Ang-1通过酪氨酸激酶/磷脂酰3激酶信号传递途径使细胞内的Mg2+库释放Mg2+,从而增加HUVECs的[Mg2+]i。 展开更多
关键词 血管生成素1 酪氨酸激酶 1-磷脂酰肌醇3-激酶
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Modulatory Effect of Rg_1 on the Activity of ProteinTyrosine Kinase of Lymphocytes in the Elderly
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作者 刘俊达 王舒 刘红涛 《Journal of Chinese Pharmaceutical Sciences》 CAS 1996年第1期7-12,共6页
The effect of Rg1,a saponin extracted froin Panax ginseng, on the phenotype,receptor and the activity of protein tyrosine kinase (PTK) of lymphocytes isolated from 7 healthy oldpersons were studied. The CD25, CD45RA a... The effect of Rg1,a saponin extracted froin Panax ginseng, on the phenotype,receptor and the activity of protein tyrosine kinase (PTK) of lymphocytes isolated from 7 healthy oldpersons were studied. The CD25, CD45RA and CD45RO phenotypes of lymphocytes were 4eter-mined by indirect immunofluorescence technique. The percentage of CD25, CD45RA and CD45ROpositive lymphocytes was 38.3%±17.3%, 46.0% 15.1%, and 52.6%±14.1% respectively after incu-bation with PHA (5 μ±/ml) for 72 hours. However, there were 58.0%±12.5%, CD25, 64.1% ± 12.4%,CD45RA, and 74.0%±8.0%, CD45RO positive cells in the presence of Rg, ( 1μg/ml) along with PHA(5 μg/ml) over the sanie period of incubation. A significant increase was induced by Rgi (P<0.05).The activities of PTK in the cytoplasm and membrane of lymphocytes were measured by ELISAmcthod after incubation with PHA or PHA+Rg1. The absorbance value of PTK activity in cytoplasmafter 72 hr incubation was 0. 120±0.020 in PHA group, but 0. 1 38±0.015 in PHA+Rg1 group. In thelymphocyte membrane, it was 0.374± 0.060 in PHA group and 0.403 ± 0.008 in PHA+Rg1 group(P<0.001). These results showed that Rgi significantly arid simultaneously increased both the PT Kactivity and the expression of phenotype of lymphocytes. 展开更多
关键词 LYMPHOCYTE RG1 RECEPTOR Protein tyrosine kinase
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Hepatitis B reactivation in chronic myeloid leukemia patients receiving tyrosine kinase inhibitor 被引量:6
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作者 Guan-Min Lai Sheng-Lei Yan +1 位作者 Cheng-Shyong Chang Chien-Yu Tsai 《World Journal of Gastroenterology》 SCIE CAS 2013年第8期1318-1321,共4页
Hepatitis B virus(HBV) reactivation is a well-recognized complication in patients with chronic HBV infection receiving cytotoxic or immunosuppressive chemotherapy.Imatinib mesylate and nilotinib are selective Bcr/Abl ... Hepatitis B virus(HBV) reactivation is a well-recognized complication in patients with chronic HBV infection receiving cytotoxic or immunosuppressive chemotherapy.Imatinib mesylate and nilotinib are selective Bcr/Abl tyrosine kinase inhibitors,which are now widely used in the treatment of patients with chronic myeloid leukemia.Although HBV reactivation induced by imatinib mesylate has been reported,nilotinib-related HBV reactivation has not been reported in the English literature.We report here 2 cases of HBV reactivation in chronic myeloid leukemia patients receiving imatinib mesylate and a novel case of nilotinib related HBV reactivation. 展开更多
关键词 Hepatitis B virus Chronic MYELOID leukemia IMATINIB MESYLATE NILOTINIB tyrosine kinase inhibitor
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Chinese consensus on management of tyrosine kinase inhibitor-associated side effects in gastrointestinal stromal tumors 被引量:6
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作者 Jian Li Ming Wang +15 位作者 Bo Zhang Xin Wu Tian-Long Lin Xiu-Feng Liu Ye Zhou Xin-Hua Zhang Hao Xu Li-Jing Shen Jing Zou Ping Lu Dong Zhang Wei-Jun Gu Mei-Xia Zhang Jian Pan Hui Cao 《World Journal of Gastroenterology》 SCIE CAS 2018年第46期5189-5202,共14页
Tyrosine kinase inhibitors(TKIs) have improved the overall survival of patients with gastrointestinal stromal tumors(GISTs), but their side effects can impact dose intensity and, consequently, the clinical benefit. To... Tyrosine kinase inhibitors(TKIs) have improved the overall survival of patients with gastrointestinal stromal tumors(GISTs), but their side effects can impact dose intensity and, consequently, the clinical benefit. To date, no guideline or consensus has been published on the TKI-associated adverse reactions. Therefore, the Chinese Society of Surgeons for Gastrointestinal Stromal Tumor of the Chinese Medical Doctor Association organized an expert panel discussion involving representatives from gastrointestinal surgery, medical oncology, cardiology, dermatology, nephrology, endocrinology, and ophthalmology to consider the systemic clinical symptoms, molecular and cellular mechanisms, and treatment recommendations of GISTs. Here, we present the resultant evidence-and experience-based consensus to guide the management of TKI-associated side events in clinical practice. 展开更多
关键词 Side effects GASTROINTESTINAL STROMAL tumor tyrosine kinase inhibitors CONSENSUS GUIDELINE China
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Philadelphia chromosome-positive leukemia stem cells in acute lymphoblastic leukemia and tyrosine kinase inhibitor therapy 被引量:4
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作者 Xavier Thomas 《World Journal of Stem Cells》 SCIE CAS 2012年第6期44-52,共9页
Leukemia stem cells(LSCs),which constitute a minority of the tumor bulk,are functionally defined on the basis of their ability to transfer leukemia into an immunodeficient recipient animal.The presence of LSCs has bee... Leukemia stem cells(LSCs),which constitute a minority of the tumor bulk,are functionally defined on the basis of their ability to transfer leukemia into an immunodeficient recipient animal.The presence of LSCs has been demonstrated in acute lymphoblastic leukemia(ALL),of which ALL with Philadelphia chromosome-positive(Ph+).The use of imatinib,a tyrosine kinase inhibitor(TKI),as part of front-line treatment and in combination with cytotoxic agents,has greatly improved the proportions of complete response and molecular remission and the overall outcome in adults with newly diagnosed Ph+ ALL.New challenges have emerged with respect to induction of resistance to imatinib via Abelson tyrosine kinase mutations.An important recent addition to the arsenal against Ph+ leukemias in general was the development of novel TKIs,such as nilotinib and dasatinib.However,in vitro experiments have suggested that TKIs have an antiproliferative but not an antiapoptotic or cytotoxic effect on the most primitive ALL stem cells.None of the TKIs in clinical use target the LSC.Second generation TKI dasatinib has been shown to have a more profound effect on the stem cell compartment but the drug was still unable to kill the most primitive LSCs.Allogeneic stem cell transplantation(SCT) remains the only curative treatment available for these patients.Several mechanisms were proposed to explain the resistance of LSCs to TKIs in addition to mutations.Hence,TKIs may be used as a bridge to SCT rather than monotherapy or combination with standard chemotherapy.Better understanding the biology of Ph+ ALL will open new avenues for effective management.In this review,we highlight recent findings relating to the question of LSCs in Ph+ ALL. 展开更多
关键词 Acute LYMPHOBLASTIC LEUKEMIA PHILADELPHIA CHROMOSOME tyrosine kinasE inhibitors LEUKEMIA stem cells Prognosis
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