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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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Advanced Lung Adenocarcinoma with EGFR 19-del Mutation Transformed into SCC after EGFR-tyrosine Kinase inhibitors Treatment:A Case report 被引量:1
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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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Game changer:How Janus kinase inhibitors are reshaping the landscape of ulcerative colitis mana
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作者 Antonio M Caballero-Mateos Guillermo Arturo Cañadas-de la Fuente 《World Journal of Gastroenterology》 SCIE CAS 2024年第35期3942-3953,共12页
Recent advancements in the treatment landscape of ulcerative colitis(UC)have ushered in a new era of possibilities,particularly with the introduction of Janus kinase(JAK)-signal transducer and activator of transcripti... Recent advancements in the treatment landscape of ulcerative colitis(UC)have ushered in a new era of possibilities,particularly with the introduction of Janus kinase(JAK)-signal transducer and activator of transcription inhibitors.These novel agents offer a paradigm shift in UC management by targeting key signaling pathways involved in inflammatory processes.With approved JAK inhibitors(JAKis),such as tofacitinib,filgotinib,and upadacitinib,clinicians now have powerful tools to modulate immune responses and gene expression,potentially revolutionizing the treatment algorithm for UC.Clinical trials have demonstrated the efficacy of JAKis in inducing and maintaining remission,presenting viable options for patients who have failed conventional therapies.Real-world data support the use of JAKis not only as first-line treatments but also in subsequent lines of therapy,particularly in patients with aggressive disease phenotypes or refractory to biologic agents.The rapid onset of action and potency of JAKis have broadened the possibilities in the management strategies of UC,offering timely relief for patients with active disease and facilitating personalized treatment approaches.Despite safety concerns,including cardiovascular risks and infections,ongoing research and post-marketing surveillance will continue to refine our understanding of the risk-benefit profile of JAKis in UC management. 展开更多
关键词 Ulcerative colitis Janus kinase inhibitors Filgotinib Tofacitinib Upadacitinib
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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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Optimal sequential therapy using tyrosine kinase inhibitors as the first-line treatment in patients with metastatic renal cell carcinoma: A nationwide multicenter study
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作者 Jung Ki Jo Seong Il Seo +11 位作者 MinYong Kang Jinsoo Chung Cheol Kwak Sung-Hoo Hong Cheryn Song Jae Young Park Chang Wook Jeong Seok Hwan Choi Sung Han Kim Eu Chang Hwang Chan Ho Lee Hakmin Lee 《Asian Journal of Urology》 CSCD 2024年第3期450-459,共10页
Objective:The purpose of the study was to identify the best sequence of therapy beginning with a tyrosine kinase inhibitor(TKI)as the first-line therapy for patients with metastatic renal cell carcinoma(mRCC)in terms ... Objective:The purpose of the study was to identify the best sequence of therapy beginning with a tyrosine kinase inhibitor(TKI)as the first-line therapy for patients with metastatic renal cell carcinoma(mRCC)in terms of overall survival(OS),progression-free survival(PFS),and rates of discontinuation and adverse effects during the treatment period.Methods:This is a retrospective,nationwide multicenter study of patients with mRCC after diagnosis at 10 different tertiary medical centers in Korea from January 1992 to December 2017.We focused on patients at either“favorable”or“intermediate”risk according to the International mRCC Database Consortium criteria,and they were followed up(median 335 days).Finally,a total of 1409 patients were selected as the study population.We generated a Cox proportional hazard model adjusted for covariates,and the different therapy schemes were statistically tested in terms of OS as well as PFS.In addition,frequencies of discontinuation and adverse events were compared among the therapy schemes.Results:Of the primary patterns of treatment sequences(24 sequences),“sunitinib epazopanib”and“sunitinibeeverolimuseimmunotherapy”showed the most beneficial results in both OS and PFS with significantly lower hazards than“sunitinib”,which is the most commonly treated agent in Korea.Considering that the“TKIeTKI”structure showed relatively higher discontinuation rates with higher adverse effects,the overall beneficial sequence would be“sunitinibeeverolimuseimmunotherapy”.Conclusion:Among several sequential therapy starting with TKIs,“sunitinibeeverolimuse immunotherapy”was found to be the best scheme for mRCC patients with“favorable”or“intermediate”risks. 展开更多
关键词 Tyrosine kinase inhibitor Metastatic renal cell carcinoma Overall survival Progression-free survival
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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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Navigating treatment resistance:Janus kinase inhibitors for ulcerative colitis
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作者 Jonathan Soldera 《World Journal of Clinical Cases》 SCIE 2024年第24期5468-5472,共5页
The management of refractory ulcerative colitis(UC)and acute severe UC(ASUC)is challenging due to the lack of standardized approaches in cases resistant to multiple treatments.In this editorial,I investigate the effic... The management of refractory ulcerative colitis(UC)and acute severe UC(ASUC)is challenging due to the lack of standardized approaches in cases resistant to multiple treatments.In this editorial,I investigate the efficacy and safety of Janus kinase inhibitors,particularly upadacitinib and tofacitinib,in controlling severe and refractory disease.I highlight a notable case report by Xu et al,which explores the case of a patient with primary nonresponse to two classes of biologics and two fecal microbiota transplants who exhibited a remarkable response to upadacitinib.Furthermore,I discuss the use of tofacitinib in refractory UC and ASUC,either as monotherapy or in combination with biologics,which has shown promising response rates.Additionally,emerging evidence of upadacitinib efficacy in ASUC is presented.Overall,these cases emphasize the complex nature of managing refractory ASUC and the potential of small-molecule therapies to achieve remission.Further research is needed to refine treatment strategies for patients with treatment-resistant UC. 展开更多
关键词 Inflammatory bowel disease Ulcerative colitis Janus kinase inhibitor Upadacitinib Tofacitinib INFLIXIMAB
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Piperlongumine in combination with EGFR tyrosine kinase inhibitors for the treatment of lung cancer cells
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作者 SHAIL RAKESH MODI TERRICK ANDEY 《Oncology Research》 SCIE 2024年第11期1709-1721,共13页
Objectives:EGFR tyrosine kinase inhibitor(EGFR-TKI)therapies such as erlotinib and gefitinib are approved for the treatment of non-small cell lung cancer(NSCLC).However,the high incidence of acquired resistance to the... Objectives:EGFR tyrosine kinase inhibitor(EGFR-TKI)therapies such as erlotinib and gefitinib are approved for the treatment of non-small cell lung cancer(NSCLC).However,the high incidence of acquired resistance to these EGFR-TKIs may preclude their effectiveness.Piperlongumine(PPL),an extract from the long pepper fruit(Piper longum),has been shown to possess anticancer properties.The purpose of the study was to investigate piperlongumine as an anticancer agent and to study a combination treatment approach with EGFR-TKIs against lung cancer cells.Methods:Anticancer efficacy of PPL,erlotinib(ERL),gefitinib(GEF),and cisplatin(CIS)were investigated in H1299 and H1975 cell lines.Cells were treated with PPL,ERL,GEF,and CIS alone,and in combination,cell viability was determined after 72 h.The mechanism of PPL-induced cytotoxicity was investigated via reactive oxygen species(ROS)induction,and apoptosis induction using acridine orange/ethidium bromide staining and flow cytometry.The effect of treatment on EGFR-mediated oncogenic signaling was investigated by immunoblotting for mitogenic and apoptotic markers.Results:PPL exhibited a potent cytotoxic effect in H1299 and H1975 cells compared to ERL,GEF,and CIS.Combination treatments of PPL with GEF and ERL showed significant reductions in cancer cells compared to control in both cell lines,which were associated with apoptotic induction,but without significant ROS induction.Compared to control,PPL with GEF significantly increased apoptotic cell death in H1975as confirmed with flow cytometry.Treatment with PPL alone and in combination induced anti-mitogenic and apoptotic responses at the molecular level.Conclusion:PPL sensitized lung cancer cells to EGFR-TKI and induced potent cytotoxic effects at low concentrations. 展开更多
关键词 Piperlongumine(PPL) Non-small cell lung cancer(NSCLC) Tyrosine kinase inhibitors(TKI) MUTATION RESISTANCE
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Clinical significance of upregulated Rho GTPase activating protein 12 causing resistance to tyrosine kinase inhibitors in hepatocellular carcinoma
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作者 Xiao-Wei Wang Yu-Xing Tang +11 位作者 Fu-Xi Li Jia-Le Wang Gao-Peng Yao Da-Tong Zeng Yu-Lu Tang Bang-Teng Chi Qin-Yan Su Lin-Qing Huang Di-Yuan Qin Gang Chen Zhen-Bo Feng Rong-Quan He 《World Journal of Gastrointestinal Oncology》 SCIE 2024年第10期4244-4263,共20页
BACKGROUND Hepatocellular carcinoma(HCC)is a major health challenge with high incidence and poor survival rates in China.Systemic therapies,particularly tyrosine kinase inhibitors(TKIs),are the first-line treatment fo... BACKGROUND Hepatocellular carcinoma(HCC)is a major health challenge with high incidence and poor survival rates in China.Systemic therapies,particularly tyrosine kinase inhibitors(TKIs),are the first-line treatment for advanced HCC,but resistance is common.The Rho GTPase family member Rho GTPase activating protein 12(ARHGAP12),which regulates cell adhesion and invasion,is a potential therapeutic target for overcoming TKI resistance in HCC.However,no studies on the expression of ARHGAP12 in HCC and its role in resistance to TKIs have been reported.AIM To unveil the expression of ARHGAP12 in HCC,its role in TKI resistance and its potential associated pathways.METHODS This study used single-cell RNA sequencing(scRNA-seq)to evaluate ARHGAP12 mRNA levels and explored its mechanisms through enrichment analysis.CellChat was used to investigate focal adhesion(FA)pathway regulation.We integrated bulk RNA data(RNA-seq and microarray),immunohistochemistry and proteomics to analyze ARHGAP12 mRNA and protein levels,correlating with clinical outcomes.We assessed ARHGAP12 expression in TKI-resistant HCC,integrated conventional HCC to explore its mechanism,identified intersecting FA pathway genes with scRNA-seq data and evaluated its response to TKI and immunotherapy.RESULTS ARHGAP12 mRNA was found to be highly expressed in malignant hepatocytes and to regulate FA.In malignant hepatocytes in high-score FA groups,MDK-[integrin alpha 6(ITGA6)+integrinβ-1(ITGB1)]showed specificity in ligand-receptor interactions.ARHGAP12 mRNA and protein were upregulated in bulk RNA,immunohistochemistry and proteomics,and higher expression was associated with a worse prognosis.ARHGAP12 was also found to be a TKI resistance gene that regulated the FA pathway.ITGB1 was identified as a crossover gene in the FA pathway in both scRNA-seq and bulk RNA.High expression of ARHGAP12 was associated with adverse reactions to sorafenib,cabozantinib and regorafenib,but not to immunotherapy.CONCLUSION ARHGAP12 expression is elevated in HCC and TKI-resistant HCC,and its regulatory role in FA may underlie the TKI-resistant phenotype. 展开更多
关键词 Hepatocellular carcinoma Focal adhesion Tyrosine kinase inhibitor Rho GTPase activating protein 12 Drug resistance Molecular mechanism BIOMARKER
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Present and prospect of transarterial chemoembolization combined with tyrosine kinase inhibitor and PD-1 inhibitor for unresectable hepatocellular carcinoma
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作者 Rui Zhang Yan-Hui Liu +2 位作者 Yu Li Nan-Nan Li Zheng Li 《World Journal of Gastrointestinal Oncology》 SCIE 2024年第11期4315-4320,共6页
In this editorial,we comment on the article(World J Gastrointest Oncol 2024;16:1236-1247),which is a retrospective study of transarterial chemoembolization(TACE)combined with multi-targeted tyrosine kinase inhibitor(T... In this editorial,we comment on the article(World J Gastrointest Oncol 2024;16:1236-1247),which is a retrospective study of transarterial chemoembolization(TACE)combined with multi-targeted tyrosine kinase inhibitor(TKI)and programmed cell death protein-1(PD-1)inhibitor for the treatment of unresectable hepatocellular carcinoma(HCC).Herein,we focus specifically on the mechanisms of this triple therapy,administration sequence and selection of each medication,and implications for future clinical trials.Based on the interaction mechanisms between medications,the triple therapy of TACE+TKI+PD-1 is proposed to complement the deficiency of each monotherapy,and achieve synergistic antitumor effects.Although this triple therapy has been evaluated by several retrospective trials,it is still controversial whether the triple therapy achieves better clinical benefits,due to the flawed study design and heterogeneity in medications.In addition,the administration sequence,which may greatly affect the clinical benefit,needs to be fully considered at clinical decision-making for obtaining better prognosis.We hope that this editorial could contribute to the design and optimization of future trials. 展开更多
关键词 Transarterial chemoembolization Multi-targeted tyrosine kinase inhibitor Programmed cell death protein-1 inhibitor Unresectable hepatocellular carcinoma Mechanism
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Advanced lung adenocarcinoma with EGFR 19-del mutation transforms into squamous cell carcinoma after EGFR tyrosine kinase inhibitor treatment
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作者 Ruo-Bing Qi Zheng-Hao Wu 《World Journal of Clinical Cases》 SCIE 2024年第32期6543-6546,共4页
In this editorial we comment on the article by Ji et al.We focus specifically on the EGFR tyrosine kinase inhibitor(EGFR-TKI)treatment and the development of drug resistance to EGFR-TKIs.
关键词 Lung adenocarcinoma Squamous cell carcinoma Histological transformation Epidermal growth factor receptor tyrosine kinase inhibitor Drug resistance
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Protein kinase inhibitors affect spermatogenic functions and blood testis barrier remodelling:A scoping review 被引量:1
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作者 Oyovwi Mega Obukohwo Onome Bright Oghenetega +4 位作者 Falajiki Yewande Faith Emojevwe Victor Rotu Arientare Rume Joseph Gregory Uchechukwu Oyeleke Abiodun Abioye 《Asian pacific Journal of Reproduction》 2023年第3期97-108,共12页
Objective:To identify the role of protein kinase in male reproduction in animal models and human spermatogenic function.Methods:This study assessed the protein kinase of male reproduction in animal models and human us... Objective:To identify the role of protein kinase in male reproduction in animal models and human spermatogenic function.Methods:This study assessed the protein kinase of male reproduction in animal models and human using different reviewed paper indexed in PubMed,Science Direct,EBSCO,Scopus,Cochrane Library,Sage Journals,and Google Scholar.Data were charted based on author,year of publication published between 1893 and 2023,country,purpose,data collection,key findings,and research focus/domain.Results:The MAPK pathway contributed to the growth,maturation,and functionality of male germ cells.We also found out that certain influencing factors categorized into hormonal/non hormonal factors and chemotoxicant,as well as heat stress expressed an inhibitory mechanism on protein kinase,thus affecting spermatogenic functions and maintenance/remodeling of the blood testis barrier,as well as the physiology of the Sertoli cells necessary for nutritional support of spermatogenesis.However,activating protein kinases pathway like the mTOR pathway as well as increased expression of peroxiredoxin-4 and L-carnitine mediated protein kinases may be useful for treating or managing male reproductive dysfunction.Conclusions:Protein kinase plays an important role in spermatogenic functions and blood testis remodeling in animal and human.Its assessment provides essential information that can guide treatment strategies aimed at improving male reproductive potential.Taken together,these recent advances highlight a future therapeutic intervention in assessing male reproductive potential.It might also be possible to look at potential targets for male contraceptives in the MAPK pathway. 展开更多
关键词 SPERMATOGENESIS Protein kinase inhibitors Sertoli cells CAPACITATION MTOR
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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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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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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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Effects of retinoic acid on proliferation,phenotype and expression of cyclin-dependent kinase inhibitors in TGF-β1-stimulated rat hepatic stellate cells 被引量:23
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作者 Guang Cun Huang Jin Sheng Zhang Yue E Zhang Department of Pathology School of Basic Medical Sciences,Fudan University.Shanghai 200032,China 《World Journal of Gastroenterology》 SCIE CAS CSCD 2000年第6期819-823,共5页
AIM To study the molecular mechanisms ofretinoic acid(RA)on proliferation andexpression of cyclin-dependent kinase inhibitors(CKI),i.e.p16,p21 and p27 in cultured rathepatic stellate cells(HSC)stimulated withtransform... AIM To study the molecular mechanisms ofretinoic acid(RA)on proliferation andexpression of cyclin-dependent kinase inhibitors(CKI),i.e.p16,p21 and p27 in cultured rathepatic stellate cells(HSC)stimulated withtransforming growth factor beta 1(TGF-β1).METHODS HSC were isolated from healthy ratlivers and cultured.After stimulated with1 mg/L TGF-β1,subcultured HSC were treatedwith or without 1 nmol/L RA.MTT assay,immunocytochemistry(ICC)for p16,p21,p27and α-smooth muscle actin(α-SMA)protein,insitu hybridization(ISH)for retinoic acidreceptor beta 2(RAR-β2)and p16,p21 and p27mRNA and quantitative image analysis(partially)were performed.RESULTS RA inhibited HSC proliferation(41.50%,P【0.05),decreased the protein levelof α-SMA(55.09%,P【0.05),and induced HSCto express RAR-β2 mRNA.In addition,RAincreased the protein level of p16(218.75%,P【0.05)and induced p21 protein expression;meanwhile,p27 was undetectable by ICC in bothcontrol and RA-treated HSC.However,RA hadno influence on the mRNA levels of p16,p21 orp27 as determined by ISH.CONCLISION Up-regulation of p16 and p21 on post-transcriptional level may contribule, in part to RA inhibition of TGF-β1-initiated rat HSC activation in vitro. 展开更多
关键词 RETINOIC acid cyclindependent kinase inhibitor hepatic stellate CELL CELL culture TRANSFORMING growth factor beta 1 liver FIBROSIS
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Protein kinase small molecule inhibitors for rheumatoid arthritis: Medicinal chemistry/clinical perspectives 被引量:5
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作者 Charles J Malemud David E Blumenthal 《World Journal of Orthopedics》 2014年第4期496-503,共8页
Medicinal chemistry strategies have contributed to the development, experimental study of and clinical trials assessment of the first type of protein kinase small molecule inhibitor to target the Janus kinase/Signal T... Medicinal chemistry strategies have contributed to the development, experimental study of and clinical trials assessment of the first type of protein kinase small molecule inhibitor to target the Janus kinase/Signal Transducers and Activators of Transcription(JAK/STAT) signaling pathway. The orally administered small molecule inhibitor, tofacitinib, is the first drug to target the JAK/STAT pathway for entry into the armamentarium of the medical therapy of rheumatoid arthritis. The introduction of tofacitinib into general rheumatologic practice coupled with increasing understanding that additional cellular signal transduction pathways including the mitogen-activated protein kinase and phosphatidylinositide-3-kinase/Akt/mammalian target of rapa-mycin pathways as well as spleen tyrosine kinase also contribute to immune-mediated inflammatory in rheumatoid arthritis makes it likely that further development of orally administered protein kinase small molecule inhibitors for rheumatoid arthritis will occur in the near future. 展开更多
关键词 CLINICAL trials Protein kinase Signal TRANSDUCTION Small molecule inhibitor RHEUMATOID ARTHRITIS
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Molecular mechanism underlying the functional loss of cyclindependent kinase inhibitors p16 and p27 in hepatocellular carcinoma 被引量:20
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作者 Yasunobu Matsuda 《World Journal of Gastroenterology》 SCIE CAS CSCD 2008年第11期1734-1740,共7页
Hepatocellular carcinoma (HCC) is one of the most common human cancers, and its incidence is still increasing in many countries. The prognosis of HCC patients remains poor, and identification of useful molecular pro... Hepatocellular carcinoma (HCC) is one of the most common human cancers, and its incidence is still increasing in many countries. The prognosis of HCC patients remains poor, and identification of useful molecular prognostic markers is required. Many recent studies have shown that functional alterations of cellcycle regulators can be observed in HCC. Among the various types of cell-cycle regulators, p16 and p27 are frequently inactivated in HCC and are considered to be potent tumor suppressors, p16, a G1-specific cell-cycle inhibitor that prevents the association of cyclindependent kinase (CDK) 4 and CDK6 with cyclin DI, is frequently inactivated in HCC via CpG methylation of its promoter region, p16 may be involved in the early steps of hepatocarcinogenesis, since p16 gene methylation has been detected in subsets of pre-neoplastic liver cirrhosis patients, p27, a negative regulator of the G1-S phase transition through inhibition of the kinase activities of Cdk2/cyclin A and Cdk2/cyclin E complexes, is now considered to be an adverse prognostic factor in HCC. In some cases of HCC with increased cell proliferation, p27 is overexpressed but inactivated by sequestration into cyclin D1-CDK4-containing complexes. Since loss of p16 is closely related to functional inactivation of p27 in HCC, investigating both p16 and p27 may be useful for precise prognostic predictions in individuals with HCC. 展开更多
关键词 Hepatocellular carcinoma Cell-cycle regulator Cyclin-dependent kinase inhibitor DNA methylation DNA methyltransferase P16 P27 FoxM1b
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Epidermal growth factor receptor tyrosine kinase inhibitors for non-small cell lung cancer 被引量:5
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作者 Kazuhiro Asami Shinji Atagi 《World Journal of Clinical Oncology》 CAS 2014年第4期646-659,共14页
First-generation epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs), including gefitinib and erlotinib, have proven to be highly effective agents for advanced non-small cell lung cancer(NSCLC) in p... First-generation epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs), including gefitinib and erlotinib, have proven to be highly effective agents for advanced non-small cell lung cancer(NSCLC) in patients harboring an activating EGFR mutation such as the exon 19 deletion mutation and L858 R. Although those reversible small molecular targeted agents provide a significant response and survival benefit, all responders eventually acquire resistance. Secondgeneration EGFR-targeting agents, such as irreversible EGFR/HER2 tyrosine kinase inhibitors and pan-HER TKIs, may improve survival further and be useful for patients who acquired resistance to first-generation EGFR-TKIs. This review discusses novel therapeutic strategies for EGFR-mutated advanced NSCLC using first- and second-generation EGFR-TKIs. 展开更多
关键词 EPIDERMAL GROWTH FACTOR RECEPTOR mutation EPIDERMAL GROWTH FACTOR RECEPTOR TYROSINE kinase inhibitors NON-SMALL cell lung cancer Secondary resistance
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Tolerance of neurite outgrowth to Rho kinase inhibitors decreased by cyclooxygenase-2 inhibitor 被引量:1
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作者 Weigang Duan Ling Que +3 位作者 Xiaoman Lv Qifeng Li Hua Yin Luyong Zhang 《Neural Regeneration Research》 SCIE CAS CSCD 2012年第34期2705-2712,共8页
In this study, PC12 Adh cells and Neuro-2a cells were treated with Rho-associated kinase inhibitors (Y27632 and Fasudil), a cyclooxygenase-1 selective inhibitor (SC560), and a cyclooxygenase-2 inhibitor (NS398).... In this study, PC12 Adh cells and Neuro-2a cells were treated with Rho-associated kinase inhibitors (Y27632 and Fasudil), a cyclooxygenase-1 selective inhibitor (SC560), and a cyclooxygenase-2 inhibitor (NS398). We found that these cells became tolerant to Rho-associated kinase inhibitors, as neurite outgrowth induced by these inhibitors diminished following more than 3 days of exposure in either cell line. The proteins cyclooxygenase-2 and cytosolic prostaglandin E synthetase were upregulated at day 3. NS398 decreased the tolerance to neurite outgrowth induction in both cell lines, whereas SC560 had almost no effect. These findings indicate that cells become tolerant to neurite outgrowth induced by Rho-associated kinase inhibitors, this is at least partly associated with upregulation of proteins involved in the cyclooxygenase-2 pathway, and cyclooxygenases-2 inhibition prevents this tolerance. 展开更多
关键词 Rho-associated kinase inhibitors Y27632 FASUDIL NEURITE cyclooxygenase 2 inhibitors drugtolerance
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