This review summarizes the therapeutic strategies and the drugs actually in development for the management of myeloma patients. Multiple myeloma is caused by the expansion of monoclonal plasma cells and secretion of M...This review summarizes the therapeutic strategies and the drugs actually in development for the management of myeloma patients. Multiple myeloma is caused by the expansion of monoclonal plasma cells and secretion of M-protein(immunoglobulins, Bence Jones protein and free light chains). Multiple myeloma still remains an incurable disease with a high incidence rate in the elderly, despite the introduction of several new therapeutic agents(bortezomib, lenalidomide and thalidomide) which have changed its natural history. The high heterogeneity of this disease leads to large differences in clinical responses to treatments. Thus, the choice of the best treatment is a difficult issue. However, the introduction of new drugs has made it possible to achieve high response rates and good quality respons-es with long-term disease control. Interactions between tumor cells and their bone marrow microenvironment play a pivotal role in the development, maintenance, and progression of myeloma, inducing also drug resistance. These knowledges have improved treatment options, leading to the approval of new drugs which not only target the malignant cell itself, but also its microenvironment. These agents are in preclinical/early clinical evaluation and they appear to further improve disease control, but their use is still not approved outside of clinical trials.展开更多
The immune system is involved in the initiation and progression of cancer. Research on cancer and immunity has contributed to the development of several clinically successful immunotherapies. These immunotherapies oft...The immune system is involved in the initiation and progression of cancer. Research on cancer and immunity has contributed to the development of several clinically successful immunotherapies. These immunotherapies often act on a single step of the cancer-immunity cycle. In recent years, the discovery of new nanomaterials has dramatically expanded the functions and potential applications of nanomaterials. In addition to acting as drug-delivery platforms, some nanomaterials can induce the immunogenic cell death(ICD) of cancer cells or regulate the profile and strength of the immune response as immunomodulators.Based on their versatility, nanomaterials may serve as an integrated platform for multiple drugs or therapeutic strategies, simultaneously targeting several steps of the cancer-immunity cycle to enhance the outcome of anticancer immune response. To illustrate the critical roles of nanomaterials in cancer immunotherapies based on cancer-immunity cycle, this review will comprehensively describe the crosstalk between the immune system and cancer, and the current applications of nanomaterials, including drug carriers, ICD inducers, and immunomodulators. Moreover, this review will provide a detailed discussion of the knowledge regarding developing combinational cancer immunotherapies based on the cancer-immunity cycle, hoping to maximize the efficacy of these treatments assisted by nanomaterials.展开更多
Immunotherapy has led to a paradigm shift in the treatment of cancer.Current cancer immunotherapies are mostly antibody-based,thus possessing advantages in regard to pharmacodynamics(e.g.,specificity and efficacy).How...Immunotherapy has led to a paradigm shift in the treatment of cancer.Current cancer immunotherapies are mostly antibody-based,thus possessing advantages in regard to pharmacodynamics(e.g.,specificity and efficacy).However,they have limitations in terms of pharmacokinetics including long half-lives,poor tissue/tumor penetration,and little/no oral bioavailability.In addition,therapeutic antibodies are immunogenic,thus may cause unwanted adverse effects.Therefore,researchers have shifted their efforts towards the development of small molecule-based cancer immunotherapy,as small molecules may overcome the above disadvantages associated with antibodies.Further,small molecule-based immunomodulators and therapeutic antibodies are complementary modalities for cancer treatment,and may be combined to elicit synergistic effects.Recent years have witnessed the rapid development of small molecule-based cancer immunotherapy.In this review,we describe the current progress in small molecule-based immunomodulators(inhibitors/agonists/degraders)for cancer therapy,including those targeting PD-1/PD-L1,chemokine receptors,stimulator of interferon genes(STING),Toll-like receptor(TLR),etc.The tumorigenesis mechanism of various targets and their respective modulators that have entered clinical trials are also summarized.展开更多
β-glucans belong to a group of biologically active natural compounds called biological response modifiers.These substances represent highly conserved structural components of cell walls in fungi,yeast,grain and seawe...β-glucans belong to a group of biologically active natural compounds called biological response modifiers.These substances represent highly conserved structural components of cell walls in fungi,yeast,grain and seaweed.Despite almost 160 years of intensive research,the exact mechanisms of their action remain unsolved.The significant role of glucans in cancer treatment,infection immunity,stress reduction and restoration of damaged bone marrow has already been established.The present review focuses on the various less known but potentially significant roles glucans might play in medicine.In summary,glucan might represent the most important natural immunomodulator.展开更多
Methotrexate has been used an immunomodulator in many autoimmune diseases,including inflammatory bowel disease. However,many physicians are unfamiliar or uncomfortable with its use in the management of inflammatory bo...Methotrexate has been used an immunomodulator in many autoimmune diseases,including inflammatory bowel disease. However,many physicians are unfamiliar or uncomfortable with its use in the management of inflammatory bowel disease. We summarize the data for use of methotrexate in common clinical scenarios:(1) steroid dependant Crohn's disease(CD);(2) maintenance of remission in steroid free CD;(3) azathioprine failures in CD;(4) in combination therapy with Anti-TNF agents in CD;(5) decreasing antibody formation to Anti-TNF therapy in CD;(6) management of fistulizing disease in CD; and(7) as well as induction and maintenance of remission in ulcerative colitis. An easy to use algorithm is provided for the busy clinician to access and safely prescribe methotrexate for their inflammatory bowel disease patients.展开更多
This editorial commented on an article in the World Journal of Gastroenterology titled“Risks of Reactivation of Hepatitis B Virus in Oncological Patients Using Tyrosine Kinase-Inhibitors:Case Report and Literature An...This editorial commented on an article in the World Journal of Gastroenterology titled“Risks of Reactivation of Hepatitis B Virus in Oncological Patients Using Tyrosine Kinase-Inhibitors:Case Report and Literature Analysis”by Colapietro et al.In this editorial,we focused on providing a more comprehensive exploration of hepatitis B virus reactivation(HBVr)associated with the usage of tyrosine kinase inhibitors(TKIs).It includes insights into the mechanisms underlying HBV reactivation,the temporal relationship between TKIs and HBV reactivation,and preventive measures.The aim is to understand the need for nucleos(t)ide analogs(NAT)and serial blood tests for early recognition of reactivation and acute liver injury,along with management strategies.TKIs are considered to be an intermediate(1%-10%)of HBVr.Current guidelines stipulate that patients receiving therapy with high or moderate risks of reactivation or recent cancer diagnosis must have at least tested hepatitis B surface antigen,anti-hepatitis B core antigen(HBc),and anti-hepatitis B surface antibody.Anti-HBc screening in highly endemic areas means people with negative tests should be vaccinated against HBV.Nucleoside or nucleotide analogs(NAs)like entecavir(ETV),tenofovir disoproxil fumarate(TDF),and tenofovir alafenamide(TAF)form the basis of HBV reactivation prophylaxis and treatment during immunosuppression.Conversely,lamivudine,telbivudine,and adefovir are generally discouraged due to their reduced antiviral efficacy and higher risk of fostering drug-resistant viral strains.However,these less effective NAs may still be utilized in cases where ETV,TDF,and TAF are not feasible treatment options.展开更多
In the treatment of central nervous system(CNS)diseases such as glioma,Alzheimer's disease(AD)and Parkinson's disease(PD),drugs are expected to reach specific areas of the brain to achieve the desired effect.A...In the treatment of central nervous system(CNS)diseases such as glioma,Alzheimer's disease(AD)and Parkinson's disease(PD),drugs are expected to reach specific areas of the brain to achieve the desired effect.Although a growing number of therapeutic targets have been identified in preclinical studies,the ones that can ultimately be used in the clinic are limited.Therefore,the research process and clinical application of drugs for treating CNS diseases are still large challenges.Physiological barriers such as the blood‒brain barrier(BBB)act as selective permeable membranes,allowing only certain molecules to enter the brain;this barrier is the major obstacle restricting the arrival of most drugs to brain lesions.Recently,nanoparticles,including lipid-based,cell-derived biomimetic,polymeric and inorganic nanoparticles,have gained increasing attention because of their ability to cross physiological barriers,and could play an important role as delivery carriers and immunomodulators.Additionally,clinical applications of nanoparticles in CNS diseases are underway.This review focuses on the progress of current research on the use of nanoparticles for the treatment of CNS diseases to provide additional insight into the treatment of CNS diseases.展开更多
Background:As reported,γ-tubulin(TuBG1)is related to the occurrence and development of various types of malignant tumors.However,its role in hepatocellular cancer(HCC)is not clear.The present study was to investigate...Background:As reported,γ-tubulin(TuBG1)is related to the occurrence and development of various types of malignant tumors.However,its role in hepatocellular cancer(HCC)is not clear.The present study was to investigate the relationship between TuBG1 and clinical parameters and survival in HCC patients.Methods:The correlation between TuBG1 and clinical parameters and survival in HCC patients was ex-plored by bioinformatics analysis.Immunohistochemistry was used for the verification.The molecular function of TuBG1 was measured using colony formation,scratch assay,trans-well assay and flow cytometry.Gene set enrichment analysis(GSEA)was used to pick up the enriched pathways,followed by investigating the target pathways using Western blotting.The tumor-immune system interactions and drug bank database(TISIDB)was used to evaluate TuBG1 and immunity.Based on the TuBG1-related immune genes,a prognostic model was constructed and was further validated internally and externally.Results:The bioinformatic analysis found high expressed TuBG1 in HCC tissue,which was confirmed us-ing immunohistochemistry and Western blotting.After silencing the TuBG1 in HCC cell lines,more G1 arrested cells were found,cell proliferation and invasion were inhibited,and apoptosis was promoted.Furthermore,the silence of TuBG1 increased the expressions of Ataxia-Telangiectasia and Rad-3(ATR),phospho-P38 mitogen-activated protein kinase(P-P38MAPK),phospho-P53(P-P53),B-cell lymphoma-2 associated X protein(Bax),cleaved caspase 3 and P21;decreased the expressions of B-cell lymphoma-2(Bcl-2),cyclin D1,cyclin E2,cyclin-dependent kinase 2(CDK2)and CDK4.The correlation analysis of immunohistochemistry and clinical parameters and survival data revealed that TuBG1 was negatively corre-lated with the overall survival.The constructed immune prognosis model could effectively evaluate the prognosis.Conclusions:The increased expression of TuBG1 in HCC is associated with poor prognosis,which might be involved in the occurrence and development of HCC.展开更多
基金Supported by Associazione Italiana per la Ricerca sul Cancro(Italian Association for Cancer Research-AIRC),Investigator Grant and the 5 per thousand Molecular Clinical Oncology Special Program,No.9965Milan,to AV,the European Commission's Seventh Framework programme(EU-FPT7)under grant agreement(OVER-My R)to AV,No.278706+2 种基金EU FPT7(2007-2013)under grant agreement to DR,No.278570grants from MIUR PRIN to RR,No.2009WCNS5C_004grants from MIUR PRIN to AV,No.2010NECHBX
文摘This review summarizes the therapeutic strategies and the drugs actually in development for the management of myeloma patients. Multiple myeloma is caused by the expansion of monoclonal plasma cells and secretion of M-protein(immunoglobulins, Bence Jones protein and free light chains). Multiple myeloma still remains an incurable disease with a high incidence rate in the elderly, despite the introduction of several new therapeutic agents(bortezomib, lenalidomide and thalidomide) which have changed its natural history. The high heterogeneity of this disease leads to large differences in clinical responses to treatments. Thus, the choice of the best treatment is a difficult issue. However, the introduction of new drugs has made it possible to achieve high response rates and good quality respons-es with long-term disease control. Interactions between tumor cells and their bone marrow microenvironment play a pivotal role in the development, maintenance, and progression of myeloma, inducing also drug resistance. These knowledges have improved treatment options, leading to the approval of new drugs which not only target the malignant cell itself, but also its microenvironment. These agents are in preclinical/early clinical evaluation and they appear to further improve disease control, but their use is still not approved outside of clinical trials.
基金supported by the National Natural Science Foundation of China(22007106,31800842,31922042 and 81771966)Technology&Innovation Commission of Shenzhen Municipality(JCYJ20180507181654186 and JCYJ20170818162637217,China)+1 种基金the Fundamental Research Funds for the Central Universities(2020-RC320-002 and 2019PT320028)the China Postdoctoral Science Foundation(2019TQ0396,China)。
文摘The immune system is involved in the initiation and progression of cancer. Research on cancer and immunity has contributed to the development of several clinically successful immunotherapies. These immunotherapies often act on a single step of the cancer-immunity cycle. In recent years, the discovery of new nanomaterials has dramatically expanded the functions and potential applications of nanomaterials. In addition to acting as drug-delivery platforms, some nanomaterials can induce the immunogenic cell death(ICD) of cancer cells or regulate the profile and strength of the immune response as immunomodulators.Based on their versatility, nanomaterials may serve as an integrated platform for multiple drugs or therapeutic strategies, simultaneously targeting several steps of the cancer-immunity cycle to enhance the outcome of anticancer immune response. To illustrate the critical roles of nanomaterials in cancer immunotherapies based on cancer-immunity cycle, this review will comprehensively describe the crosstalk between the immune system and cancer, and the current applications of nanomaterials, including drug carriers, ICD inducers, and immunomodulators. Moreover, this review will provide a detailed discussion of the knowledge regarding developing combinational cancer immunotherapies based on the cancer-immunity cycle, hoping to maximize the efficacy of these treatments assisted by nanomaterials.
基金This work was supported by the National Natural Science Foundation of China(No.82173668)Scientific Research Project of High-Level Talents(No.C1034335,China)in Southern Medical University of ChinaThousand Youth Talents Program(No.C1080094,China)from the Organization Department of the CPC Central Committee,China.
文摘Immunotherapy has led to a paradigm shift in the treatment of cancer.Current cancer immunotherapies are mostly antibody-based,thus possessing advantages in regard to pharmacodynamics(e.g.,specificity and efficacy).However,they have limitations in terms of pharmacokinetics including long half-lives,poor tissue/tumor penetration,and little/no oral bioavailability.In addition,therapeutic antibodies are immunogenic,thus may cause unwanted adverse effects.Therefore,researchers have shifted their efforts towards the development of small molecule-based cancer immunotherapy,as small molecules may overcome the above disadvantages associated with antibodies.Further,small molecule-based immunomodulators and therapeutic antibodies are complementary modalities for cancer treatment,and may be combined to elicit synergistic effects.Recent years have witnessed the rapid development of small molecule-based cancer immunotherapy.In this review,we describe the current progress in small molecule-based immunomodulators(inhibitors/agonists/degraders)for cancer therapy,including those targeting PD-1/PD-L1,chemokine receptors,stimulator of interferon genes(STING),Toll-like receptor(TLR),etc.The tumorigenesis mechanism of various targets and their respective modulators that have entered clinical trials are also summarized.
文摘β-glucans belong to a group of biologically active natural compounds called biological response modifiers.These substances represent highly conserved structural components of cell walls in fungi,yeast,grain and seaweed.Despite almost 160 years of intensive research,the exact mechanisms of their action remain unsolved.The significant role of glucans in cancer treatment,infection immunity,stress reduction and restoration of damaged bone marrow has already been established.The present review focuses on the various less known but potentially significant roles glucans might play in medicine.In summary,glucan might represent the most important natural immunomodulator.
文摘Methotrexate has been used an immunomodulator in many autoimmune diseases,including inflammatory bowel disease. However,many physicians are unfamiliar or uncomfortable with its use in the management of inflammatory bowel disease. We summarize the data for use of methotrexate in common clinical scenarios:(1) steroid dependant Crohn's disease(CD);(2) maintenance of remission in steroid free CD;(3) azathioprine failures in CD;(4) in combination therapy with Anti-TNF agents in CD;(5) decreasing antibody formation to Anti-TNF therapy in CD;(6) management of fistulizing disease in CD; and(7) as well as induction and maintenance of remission in ulcerative colitis. An easy to use algorithm is provided for the busy clinician to access and safely prescribe methotrexate for their inflammatory bowel disease patients.
文摘This editorial commented on an article in the World Journal of Gastroenterology titled“Risks of Reactivation of Hepatitis B Virus in Oncological Patients Using Tyrosine Kinase-Inhibitors:Case Report and Literature Analysis”by Colapietro et al.In this editorial,we focused on providing a more comprehensive exploration of hepatitis B virus reactivation(HBVr)associated with the usage of tyrosine kinase inhibitors(TKIs).It includes insights into the mechanisms underlying HBV reactivation,the temporal relationship between TKIs and HBV reactivation,and preventive measures.The aim is to understand the need for nucleos(t)ide analogs(NAT)and serial blood tests for early recognition of reactivation and acute liver injury,along with management strategies.TKIs are considered to be an intermediate(1%-10%)of HBVr.Current guidelines stipulate that patients receiving therapy with high or moderate risks of reactivation or recent cancer diagnosis must have at least tested hepatitis B surface antigen,anti-hepatitis B core antigen(HBc),and anti-hepatitis B surface antibody.Anti-HBc screening in highly endemic areas means people with negative tests should be vaccinated against HBV.Nucleoside or nucleotide analogs(NAs)like entecavir(ETV),tenofovir disoproxil fumarate(TDF),and tenofovir alafenamide(TAF)form the basis of HBV reactivation prophylaxis and treatment during immunosuppression.Conversely,lamivudine,telbivudine,and adefovir are generally discouraged due to their reduced antiviral efficacy and higher risk of fostering drug-resistant viral strains.However,these less effective NAs may still be utilized in cases where ETV,TDF,and TAF are not feasible treatment options.
基金supported by the National Natural Science Foundation of China(Nos.82073366 and 32100748)the 1.3.5 project for disciplines of excellence,West China Hospital,Sichuan University(No.ZYGD18007)the National Natural Science Foundation of Sichuan Province(No.2022NSFSC1642).
文摘In the treatment of central nervous system(CNS)diseases such as glioma,Alzheimer's disease(AD)and Parkinson's disease(PD),drugs are expected to reach specific areas of the brain to achieve the desired effect.Although a growing number of therapeutic targets have been identified in preclinical studies,the ones that can ultimately be used in the clinic are limited.Therefore,the research process and clinical application of drugs for treating CNS diseases are still large challenges.Physiological barriers such as the blood‒brain barrier(BBB)act as selective permeable membranes,allowing only certain molecules to enter the brain;this barrier is the major obstacle restricting the arrival of most drugs to brain lesions.Recently,nanoparticles,including lipid-based,cell-derived biomimetic,polymeric and inorganic nanoparticles,have gained increasing attention because of their ability to cross physiological barriers,and could play an important role as delivery carriers and immunomodulators.Additionally,clinical applications of nanoparticles in CNS diseases are underway.This review focuses on the progress of current research on the use of nanoparticles for the treatment of CNS diseases to provide additional insight into the treatment of CNS diseases.
基金This work was supported by grants from the National Natural Science Foundation of China(52072005 and 51872279).
文摘Background:As reported,γ-tubulin(TuBG1)is related to the occurrence and development of various types of malignant tumors.However,its role in hepatocellular cancer(HCC)is not clear.The present study was to investigate the relationship between TuBG1 and clinical parameters and survival in HCC patients.Methods:The correlation between TuBG1 and clinical parameters and survival in HCC patients was ex-plored by bioinformatics analysis.Immunohistochemistry was used for the verification.The molecular function of TuBG1 was measured using colony formation,scratch assay,trans-well assay and flow cytometry.Gene set enrichment analysis(GSEA)was used to pick up the enriched pathways,followed by investigating the target pathways using Western blotting.The tumor-immune system interactions and drug bank database(TISIDB)was used to evaluate TuBG1 and immunity.Based on the TuBG1-related immune genes,a prognostic model was constructed and was further validated internally and externally.Results:The bioinformatic analysis found high expressed TuBG1 in HCC tissue,which was confirmed us-ing immunohistochemistry and Western blotting.After silencing the TuBG1 in HCC cell lines,more G1 arrested cells were found,cell proliferation and invasion were inhibited,and apoptosis was promoted.Furthermore,the silence of TuBG1 increased the expressions of Ataxia-Telangiectasia and Rad-3(ATR),phospho-P38 mitogen-activated protein kinase(P-P38MAPK),phospho-P53(P-P53),B-cell lymphoma-2 associated X protein(Bax),cleaved caspase 3 and P21;decreased the expressions of B-cell lymphoma-2(Bcl-2),cyclin D1,cyclin E2,cyclin-dependent kinase 2(CDK2)and CDK4.The correlation analysis of immunohistochemistry and clinical parameters and survival data revealed that TuBG1 was negatively corre-lated with the overall survival.The constructed immune prognosis model could effectively evaluate the prognosis.Conclusions:The increased expression of TuBG1 in HCC is associated with poor prognosis,which might be involved in the occurrence and development of HCC.
