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Revolutionizing gastric cancer treatment:The potential of immunotherapy 被引量:2
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作者 Grigorios Christodoulidis Konstantinos Eleftherios Koumarelas Marina Nektaria Kouliou 《World Journal of Gastroenterology》 SCIE CAS 2024年第4期286-289,共4页
Gastric cancer,a prevalent malignancy worldwide,ranks sixth in terms of frequency and third in fatality,causing over a million new cases and 769000 annual deaths.Predominant in Eastern Europe and Eastern Asia,risk fac... Gastric cancer,a prevalent malignancy worldwide,ranks sixth in terms of frequency and third in fatality,causing over a million new cases and 769000 annual deaths.Predominant in Eastern Europe and Eastern Asia,risk factors include family medical history,dietary habits,tobacco use,Helicobacter pylori,and Epstein-Barr virus infections.Unfortunately,gastric cancer is often diagnosed at an advanced stage,leading to a grim prognosis,with a 5-year overall survival rate below 5%.Surgical intervention,particularly with D2 Lymphadenectomy,is the mainstay for early-stage cases but offers limited success.For advanced cases,the National Comprehensive Cancer Network recommends chemotherapy,radiation,and targeted therapy.Emerging immunotherapy presents promise,especially for unresectable or metastatic cases,with strategies like immune checkpoint inhibitors,tumor vaccines,adoptive immunotherapy,and nonspecific immunomodulators.In this Editorial,with regards to the article“Advances and key focus areas in gastric cancer immunotherapy:A comprehensive scientometric and clinical trial review”,we address the advances in the field of immunotherapy in gastric cancer and its future prospects. 展开更多
关键词 IMMUNOTHERAPY Adaptive immunotherapy Tumor vaccines Chimeric antigen receptor therapy Tumor-infiltrating lymphocytes therapy Natural killer therapy Cytokine-induced killer therapy Engineered T cell receptor therapy Immune checkpoint inhibitors
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Aptasensing biosynthesized phosphatidylserine with a AuNPs nanozyme-based colorimetric aptasensor
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作者 Sai Wang Rui Ma +4 位作者 Chengqiang Li Ling Zhang Haiyang Zhang Xuehan Li Xiangzhao Mao 《Food Science and Human Wellness》 SCIE CSCD 2024年第2期823-829,共7页
Sensitive monitoring of the target products during the biosynthesis process is crucial,and facile analytical approaches are urgently needed.Herein,phosphatidylserine(PS)was chosen as the model target,a colorimetric ap... Sensitive monitoring of the target products during the biosynthesis process is crucial,and facile analytical approaches are urgently needed.Herein,phosphatidylserine(PS)was chosen as the model target,a colorimetric aptasensor was developed for the rapid quantitation in biosynthesis samples.A chimeric aptamer was constructed with two homogeneous original PS aptamers.Specific recognition between the chimeric aptamer and PS results in the desorption of aptamer from the surface of the AuNPs nanozyme,and the peroxidase-like enzymatic activity of the AuNPs nanozyme was weakened in a relationship with the different concentrations.The developed aptasensor performed well when applied for analyzing PS in biosynthesis samples.The aptasensor offers good sensitivity and selectivity,under optimal conditions,achieving monitoring and quantitation of PS in the range of 2.5-80.0μmol/L,with a limit of detection at 536.2 nmol/L.Moreover,the aptasensor provides good accuracy,with comparison rates of 98.17%-106.40%,when compared with the HPLC-ELSD.This study provides a good reference for monitoring other biosynthesized products and promoting the development of aptamers and aptasensors in real-world applications. 展开更多
关键词 PHOSPHATIDYLSERINE Chimeric aptamer AuNPs nanozyme Colorimetric aptasensor
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Prevention of hepatitis B reactivation in patients with hematologic malignancies treated with novel systemic therapies:Who and Why?
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作者 Matteo Tonnini Clara Solera Horna Luca Ielasi 《World Journal of Gastroenterology》 SCIE CAS 2024年第5期509-511,共3页
The risk of reactivation in patients with chronic or past/resolved hepatitis B virus(HBV)infection receiving chemotherapy or immunosuppressive drugs is a wellknown possibility.The indication of antiviral prophylaxis w... The risk of reactivation in patients with chronic or past/resolved hepatitis B virus(HBV)infection receiving chemotherapy or immunosuppressive drugs is a wellknown possibility.The indication of antiviral prophylaxis with nucleo(t)side analogue is given according to the risk of HBV reactivation of the prescribed therapy.Though the advent of new drugs is occurring in all the field of medicine,in the setting of hematologic malignancies the last few years have been characterized by several drug classes and innovative cellular treatment.As novel therapies,there are few data about the rate of HBV reactivation and the decision of starting or not an antiviral prophylaxis could be challenging.Moreover,patients are often treated with a combination of different drugs,so evaluating the actual role of these new therapies in increasing the risk of HBV reactivation is difficult.First results are now available,but further studies are still needed.Patients with chronic HBV infection[hepatitis B surface antigen(HBsAg)positive]are reasonably all treated.Past/resolved HBV patients(HBsAg negative)are the actual area of uncertainty where it could be difficult choosing between prophylaxis and pre-emptive strategy. 展开更多
关键词 Hepatitis B reactivation Hepatitis B virus Antiviral prophylaxis Hematologic malignancies Chimeric antigens receptor-T cell therapy Immune checkpoint inhibitors
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Influencing factors and solution strategies of chimeric antigen receptor T-cell therapy(CAR–T)cell immunotherapy
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作者 ZHENGYI WANG LIANG ZHOU XIAOYING WU 《Oncology Research》 SCIE 2024年第9期1479-1516,共38页
Chimeric antigen receptor T-cesll therapy(CAR–T)has achieved groundbreaking advancements in clinical application,ushering in a new era for innovative cancer treatment.However,the challenges associated with implementi... Chimeric antigen receptor T-cesll therapy(CAR–T)has achieved groundbreaking advancements in clinical application,ushering in a new era for innovative cancer treatment.However,the challenges associated with implementing this novel targeted cell therapy are increasingly significant.Particularly in the clinical management of solid tumors,obstacles such as the immunosuppressive effects of the tumor microenvironment,limited local tumor infiltration capability of CAR–T cells,heterogeneity of tumor targeting antigens,uncertainties surrounding CAR–T quality,control,and clinical adverse reactions have contributed to increased drug resistance and decreased compliance in tumor therapy.These factors have significantly impeded the widespread adoption and utilization of this therapeutic approach.In this paper,we comprehensively analyze recent preclinical and clinical reports on CAR–T therapy while summarizing crucial factors influencing its efficacy.Furthermore,we aim to identify existing solution strategies and explore their current research status.Through this review article,our objective is to broaden perspectives for further exploration into CAR–T therapy strategies and their clinical applications. 展开更多
关键词 Chimeric antigen receptor T-cell therapy(CAR-T) Tumor targeting therapy Influencing factor Solution strategies
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Targeted Therapy of CEA-CAR-NK Cells Against Colorectal Cancer Cells
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作者 Xinyu Zheng Xiaomeng Chen +2 位作者 Xingzhou Xia Wenzhen Wang Qian Liu 《Proceedings of Anticancer Research》 2024年第4期13-19,共7页
Objective:Investigate the cytotoxic effect of CAR-NK cells targeting CEA on colorectal cancer cells with positive CEA expression.Methods:The mRNA and protein levels of CEA in different CRC cell lines were detected by ... Objective:Investigate the cytotoxic effect of CAR-NK cells targeting CEA on colorectal cancer cells with positive CEA expression.Methods:The mRNA and protein levels of CEA in different CRC cell lines were detected by qRT-PCR and Western blot analysis.Lentiviral transduction was used to construct CAR-NK cells and empty vector CON-NK cells targeting CEA.Fluorescence microscopy and WB were used to determine whether the cells successfully constructed and expressed CAR structures.The effector NK cells were co-cultured with target cells,and the levels of LDH,IFN-γ,and GM-CSF were detected.The killing rate of effector cells was calculated,and the release of cytokines during the killing of target cells by different effector cells was compared.Results:The expression level of CEA in colorectal cancer patients was significantly higher than that in normal samples and other tumor samples,and the prognosis survival time of patients with high CEA expression was lower than that of CRC patients with low or no CEA expression(P<0.05).The CEA expression of the HT29 cell line was significantly higher than that of the SW1116 cell line at both the mRNA and protein levels.CEA-CAR-NK92 cells and CON-NK92 cells expressed green fluorescence under a microscope,and WB results showed that CEA-CAR-NK92 cells successfully expressed the CAR structure.Compared with CON-NK92 cells and NK92 cells,CEA-CAR-NK92 cells effectively killed HT29 cells(P<0.05).CEA-CAR-NK92 cells secreted a large amount of IFN-γand GM-CSF during the killing of HT29 cells,while the cytokine secretion of CON-NK92 cells and NK92 cells was not significant(P<0.05).Conclusion:CAR-NK92 cells targeting CEA can effectively kill CEA-positive colorectal cancer cells. 展开更多
关键词 Colorectal cancer Chimeric antigen receptor Natural killer cells Carcinoembryonic antigen IMMUNOTHERAPY
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Prevention and management of hepatitis B virus reactivation in patients with hematological malignancies in the targeted therapy era 被引量:10
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作者 Joyce Wing Yan Mak Alvin Wing Hin Law +3 位作者 Kimmy Wan Tung Law Rita Ho Carmen Ka Man Cheung Man Fai Law 《World Journal of Gastroenterology》 SCIE CAS 2023年第33期4942-4961,共20页
Hepatitis due to hepatitis B virus(HBV)reactivation can be serious and potentially fatal,but is preventable.HBV reactivation is most commonly reported in patients receiving chemotherapy,especially rituximab-containing... Hepatitis due to hepatitis B virus(HBV)reactivation can be serious and potentially fatal,but is preventable.HBV reactivation is most commonly reported in patients receiving chemotherapy,especially rituximab-containing therapy for hematological malignancies and those receiving stem cell transplantation.Patients with inactive and even resolved HBV infection still have persistence of HBV genomes in the liver.The expression of these silent genomes is controlled by the immune system.Suppression or ablation of immune cells,most importantly B cells,may lead to reactivation of seemingly resolved HBV infection.Thus,all patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen(HBsAg)and antibody to hepatitis B core antigen.Patients found to be positive for HBsAg should be given prophylactic antiviral therapy.For patients with resolved HBV infection,there are two approaches.The first is pre-emptive therapy guided by serial HBV DNA monitoring,and treatment with antiviral therapy as soon as HBV DNA becomes detectable.The second approach is prophy-lactic antiviral therapy,particularly for patients receiving high-risk therapy,especially anti-CD20 monoclonal antibody or hematopoietic stem cell transplantation.Entecavir and tenofovir are the preferred antiviral choices.Many new effective therapies for hematological malignancies have been introduced in the past decade,for example,chimeric antigen receptor(CAR)-T cell therapy,novel monoclonal antibodies,bispecific antibody drug conjugates,and small molecule inhibitors,which may be associated with HBV reactivation.Although there is limited evidence to guide the optimal preventive measures,we recommend antivi-ral prophylaxis in HBsAg-positive patients receiving novel treatments,including Bruton’s tyrosine kinase inhibitors,B-cell lymphoma 2 inhibitors,and CAR-T cell therapy.Further studies are needed to determine the risk of HBV reactivation with these agents and the best prophylactic strategy. 展开更多
关键词 Hepatitis B Hematologic neoplasms Chimeric antigen receptor-T cell therapy Monoclonal antibodies Bruton’s tyrosine kinase inhibitors Antiviral agents
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Facing challenges with hope:universal immune cells for hematologic malignancies 被引量:3
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作者 Yuqing Wang Ruihao Huang +3 位作者 Zheng Wang Jingkang Xiong Xiaoqi Wang Xi Zhang 《Cancer Biology & Medicine》 SCIE CAS CSCD 2023年第4期229-247,共19页
Many patients have achieved a favorable overall survival rate since allogenic hematopoietic stem cell transplantation(allo-HSCT)has been widely implemented to treat hematologic malignancies.However,graft-versus-host d... Many patients have achieved a favorable overall survival rate since allogenic hematopoietic stem cell transplantation(allo-HSCT)has been widely implemented to treat hematologic malignancies.However,graft-versus-host disease(GVHD)and complications of immunosuppressive drugs after allo-HSCT are the main causes of non-relapse mortality and a poor quality of life.In addition,GVHD and infusion-induced toxicity still occur with donor lymphocyte infusions(DLIs)and chimeric antigen receptor(CAR)T-cell therapy.Because of the special immune tolerance characteristics and anti-tumor ability of universal immune cells,universal immune cell therapy may strongly reduce GVHD,while simultaneously reducing tumor burden.Nevertheless,widespread application of universal immune cell therapy is mainly restricted by poor expansion and persistence efficacy.Many strategies have been applied to improve universal immune cell proliferation and persistence efficacy,including the use of universal cell lines,signaling regulation and CAR technology.In this review we have summarized current advances in universal immune cell therapy for hematologic malignancies with a discussion of future perspectives. 展开更多
关键词 Universal immune cells graft-versus-host disease immune tolerance chimeric antigen receptor
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Tumor neoantigens: Novel strategies for application of cancer immunotherapy 被引量:3
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作者 HANYANG GUAN YUE WU +10 位作者 LU LI YABING YANG SHENGHUI QIU ZHAN ZHAO XIAODONG CHU JIASHUAI HE ZUYANG CHEN YIRAN ZHANG HUI DING JINGHUA PAN YUNLONG PAN 《Oncology Research》 SCIE 2023年第4期437-448,共12页
Neoantigen-targeted immunotherapy is a rapidly advancing field that holds great promise for treating cancer.The recognition of antigens by immune cells is a crucial step in tumor-specific killing,and neoantigens gener... Neoantigen-targeted immunotherapy is a rapidly advancing field that holds great promise for treating cancer.The recognition of antigens by immune cells is a crucial step in tumor-specific killing,and neoantigens generated by mutations in cancer cells possess high immunogenicity and are selectively expressed in tumor cells,making them an attractive therapeutic target.Currently,neoantigens find utility in various domains,primarily in the realm of neoantigen vaccines such as DC vaccines,nucleic acid vaccines,and synthetic long peptide vaccines.Additionally,they hold promise in adoptive cell therapy,encompassing tumor-infiltrating cells,T cell receptors,and chimeric antigen receptors which are expressed by genetically modified T cells.In this review,we summarized recent progress in the clinical use of tumor vaccines and adoptive cell therapy targeting neoantigens,discussed the potential of neoantigen burden as an immune checkpoint in clinical settings.With the aid of state-of-the-art sequencing and bioinformatics technologies,together with significant advancements in artificial intelligence,we anticipated that neoantigens will be fully exploited for personalized tumor immunotherapy,from screening to clinical application. 展开更多
关键词 IMMUNOTHERAPY Tumor vaccine Adoptive T cell therapy Chimeric antigen receptor
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Donor-derived CD 19 CAR-T Cells versus Chemotherapy Plus Donor Lymphocyte Infusion for Treatment of Recurrent CD 19-positive B-ALL after Allogeneic Hematopoietic Stem Cell Transplantation 被引量:4
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作者 Xu TAN Xiao-qi WANG +11 位作者 Cheng ZHANG Xian-lan ZHAO Han YAO Guo CHEN Ying-ying MA Qin WEN Lei GAO Li GAO Pei-yan KONG Yan SHEN Xi ZHANG Shi-feng LOU 《Current Medical Science》 SCIE CAS 2023年第4期733-740,共8页
Objective:This study aimed to compare the efficacy of anti-CD19 chimeric antigen receptor T cells(CAR-T cells)versus chemotherapy plus donor lymphocyte infusion(chemo-DLI)for treating relapsed CD 19-positive B-cell ac... Objective:This study aimed to compare the efficacy of anti-CD19 chimeric antigen receptor T cells(CAR-T cells)versus chemotherapy plus donor lymphocyte infusion(chemo-DLI)for treating relapsed CD 19-positive B-cell acute lymphoblastic leukemia(B-ALL)after allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods:Clinical data of 43 patients with B-ALL who relapsed after allo-HSCT were retrospectively analyzed.Twenty-two patients were treated with CAR-T cells(CAR-T group),and 21 with chemotherapy plus DLI(chemo-DLI group).The complete remission(CR)and minimal residual disease(MRD)-negative CR rates,leukemia-free survival(LFS)rate,overall survival(OS)rate,and incidence of acute graft-versus-host disease(aGVHD),cytokine release syndrome(CRS)and immune effector cell-associated neurotoxicity syndrome(ICANS)were compared between the two groups.Results:The CR and MRD-negative CR rates in the CAR-T group(77.3%and 61.5%)were significantly higher than those in the chemo-DLI group(38.1%and 23.8%)(P=0.008 and P=0.003).The 1-and 2-year LFS rates in the CAR-T group were superior to those in the chemo-DLI group:54.5%and 50.0%vs.9.5%and 4.8%(P=0.0001 and P=0.00004).The 1-and 2-year OS rates in the CAR-T versus chemo-DLI group were 59.1%and 54.5%vs.19%and 9.5%(P=0.011 and P=0.003).Six patients(28.6%)with grade 2-4 aGVHD were identified in the chemo-DLI group.Two patients(9.1%)in the CAR-T group developed grade 1-2 aGVHD.Nineteen patients(86.4%)developed CRS in the CAR-T group,comprising grade 1-2 CRS in 13 patients(59.1%)and grade 3 CRS in 6 patients(27.3%).Two patients(9.1%)developed grade 1-2 ICANS.Conclusion:Donor-derived anti-CD19 CAR-T-cell therapy may be better,safer,and more effective than chemo-DLI for B-ALL patients who relapse after allo-HSCT. 展开更多
关键词 CD19-positive B-cell acute lymphoblastic leukemia relapse donor-derived CD19 chimeric antigen receptor T cells chemo-donor lymphocyte infusion
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Molecular and cellular changes in the post-traumatic spinal cord remodeling after autoinfusion of a genetically-enriched leucoconcentrate in a mini-pig model 被引量:2
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作者 Maria Aleksandrovna Davleeva Ravil Rasimovich Garifulin +9 位作者 Farid Vagizovich Bashirov Andrei Aleksandrovich Izmailov Leniz Faritovich Nurullin Ilnur Ildusovich Salafutdinov Dilara Zilbarovna Gatina Dmitrij Nikolaevich Shcherbinin Andrei Aleksandrovich Lysenko Irina Leonidovna Tutykhina Maksim Mikhailovich Shmarov Rustem Robertovich Islamov 《Neural Regeneration Research》 SCIE CAS CSCD 2023年第7期1505-1511,共7页
Post-traumatic spinal cord remodeling includes both degenerating and regenerating processes,which affect the potency of the functional recovery after spinal cord injury(SCI).Gene therapy for spinal cord injury is prop... Post-traumatic spinal cord remodeling includes both degenerating and regenerating processes,which affect the potency of the functional recovery after spinal cord injury(SCI).Gene therapy for spinal cord injury is proposed as a promising therapeutic strategy to induce positive changes in remodeling of the affected neural tissue.In our previous studies for delivering the therapeutic genes at the site of spinal cord injury,we developed a new approach using an autologous leucoconcentrate transduced ex vivo with chimeric adenoviruses(Ad5/35)carrying recombinant cDNA.In the present study,the efficacy of the intravenous infusion of an autologous genetically-enriched leucoconcentrate simultaneously producing recombinant vascular endothelial growth factor(VEGF),glial cell line-derived neurotrophic factor(GDNF),and neural cell adhesion molecule(NCAM)was evaluated with regard to the molecular and cellular changes in remodeling of the spinal cord tissue at the site of damage in a model of mini-pigs with moderate spinal cord injury.Experimental animals were randomly divided into two groups of 4 pigs each:the therapeutic(infused with the leucoconcentrate simultaneously transduced with a combination of the three chimeric adenoviral vectors Ad5/35‐VEGF165,Ad5/35‐GDNF,and Ad5/35‐NCAM1)and control groups(infused with intact leucoconcentrate).The morphometric and immunofluorescence analysis of the spinal cord regeneration in the rostral and caudal segments according to the epicenter of the injury in the treated animals compared to the control mini-pigs showed:(1)higher sparing of the grey matter and increased survivability of the spinal cord cells(lower number of Caspase-3-positive cells and decreased expression of Hsp27);(2)recovery of synaptophysin expression;(3)prevention of astrogliosis(lower area of glial fibrillary acidic protein-positive astrocytes and ionized calcium binding adaptor molecule 1-positive microglial cells);(4)higher growth rates of regeneratingβIII-tubulin-positive axons accompanied by a higher number of oligodendrocyte transcription factor 2-positive oligodendroglial cells in the lateral corticospinal tract region.These results revealed the efficacy of intravenous infusion of the autologous genetically-enriched leucoconcentrate producing recombinant VEGF,GDNF,and NCAM in the acute phase of spinal cord injury on the positive changes in the post-traumatic remodeling nervous tissue at the site of direct injury.Our data provide a solid platform for a new ex vivo gene therapy for spinal cord injury and will facilitate further translation of regenerative therapies in clinical neurology. 展开更多
关键词 autologous genetically-enriched leucoconcentrate chimeric adenoviral vector gene therapy glial cell line-derived neurotrophic factor MINI-PIG neural cell adhesion molecule spinal cord contusion injury vascular endothelial growth factor
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Recent advances in treatment of nodal and gastrointestinal follicular lymphoma 被引量:2
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作者 Takuya Watanabe 《World Journal of Gastroenterology》 SCIE CAS 2023年第23期3574-3594,共21页
Follicular lymphoma(FL)is the most common low-grade lymphoma,and although nodal FL is highly responsive to treatment,the majority of patients relapse repeatedly,and the disease has been incurable with a poor prognosis... Follicular lymphoma(FL)is the most common low-grade lymphoma,and although nodal FL is highly responsive to treatment,the majority of patients relapse repeatedly,and the disease has been incurable with a poor prognosis.However,primary FL of the gastrointestinal tract has been increasingly detected in Japan,especially due to recent advances in small bowel endoscopy and increased opportunities for endoscopic examinations and endoscopic diagnosis.However,many cases are detected at an early stage,and the prognosis is good in many cases.In contrast,in Europe and the United States,gastrointestinal FL has long been considered to be present in 12%-24%of Stage-IV patients,and the number of advanced gastrointestinal cases is expected to increase.This editorial provides an overview of the recent therapeutic advances in nodal FL,including antibody-targeted therapy,bispecific antibody therapy,epigenetic modulation,and chimeric antigen receptor T-cell therapy,and reviews the latest therapeutic manuscripts published in the past year.Based on an understanding of the therapeutic advances in nodal FL,we also discuss future possibilities for gastroenterologists to treat gastrointestinal FL,especially in advanced cases. 展开更多
关键词 Nodal and gastrointestinal follicular lymphoma Antibody-based therapy Bispecific antibody therapy Phosphatidylinositol-3 kinase inhibitor Epigenetic modulator Chimeric antigen receptor-T cell therapy
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Population genetics of marmosets in Asian primate research centers and loci associated with epileptic risk revealed by whole-genome sequencing 被引量:1
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作者 Xiangyu Yang Yafei Mao +11 位作者 Xuan-Kai Wang Dong-Ni Ma Zhen Xu Neng Gong Barbara Henning Xu Zhang Guang He Yong-Yong Shi Evan EEichler Zhi-Qiang Li Eiki Takahashi Wei-Dong Li 《Zoological Research》 SCIE CSCD 2023年第5期837-847,共11页
The common marmoset(Callithrix jacchus)has emerged as a valuable nonhuman primate model in biomedical research with the recent release of high-quality reference genome assemblies.Epileptic marmosets have been independ... The common marmoset(Callithrix jacchus)has emerged as a valuable nonhuman primate model in biomedical research with the recent release of high-quality reference genome assemblies.Epileptic marmosets have been independently reported in two Asian primate research centers.Nevertheless,the population genetics within these primate centers and the specific genetic variants associated with epilepsy in marmosets have not yet been elucidated.Here,we characterized the genetic relationships and risk variants for epilepsy in 41 samples from two epileptic marmoset pedigrees using whole-genome sequencing.We identified 14558184 single nucleotide polymorphisms(SNPs)from the 41 samples and found higher chimerism levels in blood samples than in fingernail samples.Genetic analysis showed fourth-degree of relatedness among marmosets at the primate centers.In addition,SNP and copy number variation(CNV)analyses suggested that the WW domain-containing oxidoreductase(WWOX)and Tyrosine-protein phosphatase nonreceptor type 21(PTPN21)genes may be associated with epilepsy in marmosets.Notably,KCTD18-like gene deletion was more common in epileptic marmosets than control marmosets.This study provides valuable population genomic resources for marmosets in two Asian primate centers.Genetic analyses identified a reasonable breeding strategy for genetic diversity maintenance in the two centers,while the case-control study revealed potential risk genes/variants associated with epilepsy in marmosets. 展开更多
关键词 Common marmoset(Callithrix jacchus) Population genetics Whole-genome sequencing Genetic chimerism Epilepsy Risk locus
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Immunotherapy in glioblastoma treatment:Current state and future prospects 被引量:1
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作者 Samuel Luca Rocha Pinheiro Fabian Fellipe Bueno Lemos +7 位作者 Hanna Santos Marques Marcel Silva Luz Luís Guilherme de Oliveira Silva Clara Faria Souza Mendes dos Santos Karolaine da Costa Evangelista Mariana Santos Calmon Matheus Sande Loureiro Fabrício Freire de Melo 《World Journal of Clinical Oncology》 CAS 2023年第4期138-159,共22页
Glioblastoma remains as the most common and aggressive malignant brain tumor,standing with a poor prognosis and treatment prospective.Despite the aggressive standard care,such as surgical resection and chemoradiation,... Glioblastoma remains as the most common and aggressive malignant brain tumor,standing with a poor prognosis and treatment prospective.Despite the aggressive standard care,such as surgical resection and chemoradiation,median survival rates are low.In this regard,immunotherapeutic strategies aim to become more attractive for glioblastoma,considering its recent advances and approaches.In this review,we provide an overview of the current status and progress in immunotherapy for glioblastoma,going through the fundamental knowledge on immune targeting to promising strategies,such as Chimeric antigen receptor T-Cell therapy,immune checkpoint inhibitors,cytokine-based treatment,oncolytic virus and vaccine-based techniques.At last,it is discussed innovative methods to overcome diverse challenges,and future perspectives in this area. 展开更多
关键词 GLIOBLASTOMA IMMUNOTHERAPY Tumor microenvironment Chimeric antigen receptor T cell Oncolytic viruses Immune-checkpoint inhibitors Brain cancer
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Immunotherapy for advanced or recurrent hepatocellular carcinoma 被引量:1
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作者 Ying-Zhe Luo Hong Zhu 《World Journal of Gastrointestinal Oncology》 SCIE 2023年第3期405-424,共20页
Hepatocellular carcinoma(HCC)is associated with high morbidity and mortality,and is prone to intra-and extrahepatic metastasis due to the anatomical and functional characteristics of the liver.Due to the complexity an... Hepatocellular carcinoma(HCC)is associated with high morbidity and mortality,and is prone to intra-and extrahepatic metastasis due to the anatomical and functional characteristics of the liver.Due to the complexity and high relapse rate associated with radical surgery or radiofrequency ablation,immune checkpoint inhibitors(ICIs)are increasingly being used to treat HCC.Several immunotherapeutic agents,along with their combinations,have been clinically approved to treat advanced or recurrent HCC.This review discusses the leading ICIs in practice and those currently undergoing randomized phase 1-3 trials as monotherapy or combination therapy.Furthermore,we summarize the rapidly developing alternative strategies such as chimeric antigen receptor-engineered T cell therapy and tumor vaccines.Combination therapy is a promising potential treatment option.These immunotherapies are also summarized in this review,which provides insights into the advantages,limitations,and novel angles for future research in establishing viable and alternative therapies against HCC. 展开更多
关键词 Recurrent hepatocellular carcinoma IMMUNOTHERAPY Immune checkpoint inhibitor Chimeric antigen receptor-engineered T cell Oncolytic virus Tumor vaccine
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Integration of molecular testing for the personalized management of patients with diffuse large B-cell lymphoma and follicular lymphoma
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作者 Ruth Stuckey Hugo Luzardo Henríquez +3 位作者 Haridian de la Nuez Melian JoséCarlos Rivero Vera Cristina Bilbao-Sieyro María Teresa Gómez-Casares 《World Journal of Clinical Oncology》 CAS 2023年第4期160-170,共11页
Diffuse large B-cell lymphoma(DLBCL)and follicular lymphoma(FL)are the most common forms of aggressive and indolent lymphoma,respectively.The majority of patients are cured by standard R-CHOP immunochemotherapy,but 30... Diffuse large B-cell lymphoma(DLBCL)and follicular lymphoma(FL)are the most common forms of aggressive and indolent lymphoma,respectively.The majority of patients are cured by standard R-CHOP immunochemotherapy,but 30%–40%of DLBCL and 20%of FL patients relapse or are refractory(R/R).DLBCL and FL are phenotypically and genetically hereterogenous B-cell neoplasms.To date,the diagnosis of DLBCL and FL has been based on morphology,immunophenotyping and cytogenetics.However,next-generation sequencing(NGS)is widening our understanding of the genetic basis of the B-cell lymphomas.In this review we will discuss how integrating the NGS-based characterization of somatic gene mutations with diagnostic or prognostic value in DLBCL and FL could help refine B-cell lymphoma classification as part of a multidisciplinary pathology work-up.We will also discuss how molecular testing can identify candidates for clinical trials with targeted therapies and help predict therapeutic outcome to currently available treatments,including chimeric antigen receptor T-cell,as well as explore the application of circulating cell-free DNA,a non-invasive method for patient monitoring.We conclude that molecular analyses can drive improvements in patient outcomes due to an increased understanding of the different pathogenic pathways affected by each DLBCL subtype and indolent FL vs R/R FL. 展开更多
关键词 Next-generation sequencing PROGNOSIS Molecular analysis Targeted therapy Chimeric antigen receptor T-cell therapy Personalized medicine
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“Too Soon on Earth”: A Biophilosophical Model of Schizophrenia. Some Implications for Humanoid Robots
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作者 Bernhard J. Mitterauer 《Advances in Bioscience and Biotechnology》 CAS 2023年第1期34-47,共14页
This paper presents a new explanatory model for schizophrenia based upon philosophical, molecular and neurobiological hypotheses as well as on years of experience in observing and treating these patients. To start wit... This paper presents a new explanatory model for schizophrenia based upon philosophical, molecular and neurobiological hypotheses as well as on years of experience in observing and treating these patients. To start with, a novel interpretation of the Hegelian concept of mediation is presented. Mediation is defined as the rejection of non-realizable programs, such as thoughts and ideas, at a certain point in time in the evolution of a living system. Whenever a system treats non-realizable programs as if they were realizable, its ability to “test the reality” is lost, and consequently a loss of ego-boundaries may occur. On the molecular level, I will try to show how “non-splicing” of introns during the mRNA splicing process is equivalent to a loss of the rejection function corresponding to mediation. At the cellular level in the brain, mediation can be explained in terms of glial-neuronal interactions. Glia exert a spatio-temporal boundary setting function determining the grouping of neurons into functional units. Mutations in genes that result in non-splicing of introns can produce truncated (“chimeric”) neurotransmitter receptors. I propose that such dysfunctional receptors are generated in glial cells and that they cannot interact properly with their cognate neurotransmitters. The glia will then lose their inhibitory-rejecting function with respect to the information processing within neuronal networks. This loss of glial boundary setting could be an explanation for the loss of ego or body boundaries in schizophrenia. Pertinent examples of case studies are given attempting to deduce the main symptoms of schizophrenia from the proposed hypothesis. Some implications for the design of delusional robots are also discussed. Finally, the evolutionary potency of non-coding introns is philosophically interpreted that schizophrenics may be “too soon on earth”. 展开更多
关键词 Non-Splicing of Introns Chimeric Glial Receptors Loss of Glial Boundary Setting Disordered Mediation Loss of Ego-Boundaries SCHIZOPHRENIA Evolutionary Potency Delusional Robots
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Chimeric ALT Perforator-Free Flap with Vastus Lateralis Muscle for the Obliteration of the Intrathoracic Dead Space Post-Pneumonectomy: A Case Report
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作者 Nelson Oduor Ouma Daniel Odhiambo Otieno +1 位作者 Lee Njagi Munge Ferdinand Wanjala Nang’ole 《Modern Plastic Surgery》 2023年第3期63-73,共11页
Chest wall reconstruction is a surgical procedure aimed at restoring the integrity and function of the chest wall, which may be damaged due to trauma, cancer, infection, or congenital defects. The chest wall plays a v... Chest wall reconstruction is a surgical procedure aimed at restoring the integrity and function of the chest wall, which may be damaged due to trauma, cancer, infection, or congenital defects. The chest wall plays a vital role in protecting the thoracic organs, supporting the respiratory system, and maintaining the shape of the chest. Therefore, any defect or deformity of the chest wall can have significant functional and aesthetic consequences for the patient. The authors present a case report at Kenyatta National Hospital (KNH) of a dyspneic 47-year-old male patient with a right anterolateral chest wall defect post-pneumonectomy previously complicated by bronchopleural fistula. Past attempts at the chest wall reconstruction had utilized the ipsilateral latissimus dorsi muscle, pectoralis major muscle, and the omental pedicled flaps with limited success. A chimeric anterolateral thigh (ALT) perforator-free flap with vastus lateralis (VL) muscle was used to obliterate the post-pneumonectomy intrathoracic dead space and to provide a cutaneous paddle. This case report aims to show the versatility of the ALT flap for chest wall reconstruction to prevent the post-pneumonectomy syndrome associated with tracheal deviation, inspiratory stridor, and exertional dyspnea. In conclusion, chest wall reconstruction with obliteration of intrathoracic dead space post-pneumonectomy is challenging and needs careful planning and execution. 展开更多
关键词 Chest Wall Reconstruction Bronchopleural Fistula PNEUMONECTOMY Chimeric ALT Flap Intrathoracic Dead Spacepost-Pneumonectomy
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Cotton Plants Transformed with the Activated Chimeric Cry1Ac and API-B Genes 被引量:12
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作者 郭洪年 吴家和 +6 位作者 陈晓英 罗晓丽 卢睿 石跃进 秦红敏 肖娟丽 田颖川 《Acta Botanica Sinica》 CSCD 2003年第1期108-113,共6页
A chimeric gene, Bt29K, composed of coding sequences of activated Cry1Ac insecticidal protein and an endoplasm reticulum-retarding signal peptide, was synthesized. A plant expression vector containing two expression c... A chimeric gene, Bt29K, composed of coding sequences of activated Cry1Ac insecticidal protein and an endoplasm reticulum-retarding signal peptide, was synthesized. A plant expression vector containing two expression cassettes for the Bt29K and API-B genes was constructed. These two insect-resistant genes were transferred into two cotton ( Gossypium hirsutum L.) varieties ( or lines) via Agrobacterium-mediated transformation and nine homozygous transgenic cotton lines showing a mortality of 90.0% - 99.7% to cotton ballworm (Heliothis armigera) larvae and good agronomic traits were selected through six generations. Molecular biology analysis revealed that one or two copies of the insecticidal protein genes were integrated into the transgenic cotton genome and activated Cry1Ac and API-B protein expression was at a level of 0.17% and 0.09% of the total soluble protein in the transgenic cotton leaves, respectively. Comparison of the insect-resistance of the homozygous lines expressing the activated chimeric Cry1Ac and API-B with that expressing Cry1Ac only revealed that the insect-resistance of the former is apparently higher than the latter. These results also indicate that the strategy to construct a plant expression vector expressing two different insect-resistant genes reported here is reasonable. 展开更多
关键词 synthetic chimeric Cry1Ac gene arrowhead proteinase inhibitor gene insect-resistant transgenic cotton plants
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Obtaining High Pest_resistant Transgenic Upland Cotton Cultivars Carrying cry1Ac3 Gene Driven by Chimeric OM Promoter 被引量:5
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作者 陈宛新 肖桂芳 朱祯 《Acta Botanica Sinica》 CSCD 2002年第8期963-970,共8页
Hypocotyl segments from aseptic seedlings of two important cultivars of upland cotton ( Gossypium hirsutum L.) in Northwest China, 'Xinluzao_1', 'Jinmian_7', 'Jinmian_12' and 'Jihe_321&#... Hypocotyl segments from aseptic seedlings of two important cultivars of upland cotton ( Gossypium hirsutum L.) in Northwest China, 'Xinluzao_1', 'Jinmian_7', 'Jinmian_12' and 'Jihe_321' were transformed respectively by two efficient plant expression plasmids pBinMoBc and pBinoBc via Agrobacterium tumefaciens . In pBinMoBc, cry 1Ac3 gene, which encodes the Bt toxin, is under the control of chimeric OM promoter. In pBinoBc, it is under control of CaMV 35S promoter. After co_cultivation with Agrobacterium tumefimpfaciens LBA4404 (containing pBinMoBc or pBinoBc), kanamycin_resistant selection, somatic embryos were induced and regenerated plants were obtained. Then the regenerated plantlets were grafted to untransformed stocks in greenhouse to produce descendants. The integration of cry 1Ac3 gene and its expression in T 2 generation of transgenic cotton plants were confirmed by Southern hybridization and Western blotting. The analyses of insect bioassay indicated that the transgenic plants of both constructions have significant resistance to the larvae of cotton bollworm ( Heliothis armigera ) and that cry 1Ac3 gene driven by chimeric OM promoter could endue T 2 generation cotton with high pest_resistant ability, implicating that it has a profound application in genetic engineering to breed new pest_resistant cotton varieties. 展开更多
关键词 upland cotton insect_resistant cotton transgenic plant Agrobacterium tumefaciens cry 1Ac3 gene chimeric promoter
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胼胝体压部神经通路在文字、物体与面孔加工中的作用 被引量:2
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作者 单春雷 翁旭初 +5 位作者 王彤 于美霞 丛芳 赵晓瑜 吕志宿 朱仁敬 《中国康复》 2010年第6期426-429,共4页
目的:揭示胼胝体压部神经通路在文字、物体与面孔加工中的作用。方法:利用一系列认知神经心理学方法,对1例(KY)胼胝体压部合并左腹内侧枕颞区梗死患者进行自然视野和左右分视野速视呈现及注视中央点速视呈现汉字、拼音的朗读检测;对自... 目的:揭示胼胝体压部神经通路在文字、物体与面孔加工中的作用。方法:利用一系列认知神经心理学方法,对1例(KY)胼胝体压部合并左腹内侧枕颞区梗死患者进行自然视野和左右分视野速视呈现及注视中央点速视呈现汉字、拼音的朗读检测;对自然视野呈现的物体和名人面孔和对注视中央点速视的Chimeric物体图片进行命名;对Chimeric面孔(半男半女)进行性别判断;并利用弥散张量纤维束示踪技术(DTT)确定胼胝体压部纤维束受损情况。同时与1例(CYH)仅左腹内侧枕颞区梗死但不合并胼胝体压部损伤、接受类似检查的患者对照。结果:KY对于自然视野、注视中央点速视呈现的汉字、拼音均出现左半错读;对左右分视野速视的汉字、拼音出现左视野失读;对于自然视野呈现的物体和名人面孔出现部分失认;对于注视中央点速视的Chimeric物体和面孔图片以左半为主进行命名和判断,并且未辨认出为Chimeric图片。DTT显示通过胼胝体压部的枕大钳纤维束通路几乎完全中断。CYH的汉字朗读、物体及面孔识别均正常,能够分辨出Chimeric图片。结论:胼胝体压部神经通路在左/右枕(右/左视野)的文字、物体与面孔视觉信息的传递及视觉整合的过程中起到必要的作用。 展开更多
关键词 胼胝体压部 左半错读 左视野失读 物体失认 Chimeric物体 Chimeric面孔
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