BACKGROUND Bone metastasis has various negative impacts.Activities of daily living(ADL)and quality of life(QOL)can be significantly decreased,survival may be impacted,and medical expenses may increase.It is estimated ...BACKGROUND Bone metastasis has various negative impacts.Activities of daily living(ADL)and quality of life(QOL)can be significantly decreased,survival may be impacted,and medical expenses may increase.It is estimated that at least 5%cancer patients might be suffering from bone metastases.In 2016,we published the Comprehensive Guidelines for the Diagnosis and Treatment of Bone Metastasis.Since then,the therapeutic outcomes for patients have gradually improved.As life expectancy is a major determinant of surgical intervention,the strategy should be modified if the prolongation of survival is to be achieved.AIM To monitor how bone metastasis treatment has changed before and after launch of our guidelines for bone metastasis.METHODS For advanced cancer patients with bone metastasis who visited the Department of Clinical Oncology at Akita University hospital between 2012 and 2023,parameters including the site and number of bone metastases,laboratory data,and survival time,were extracted from electronic medical records and the Katagiri score was calculated.The association with survival was determined for each factor.RESULTS Data from 136 patients were obtained.The 1-year survival rate for the poor prognosis group with a higher Katagiri score was 20.0%in this study,which was 6%and an apparent improvement from 2014 when the scoring system was developed.Other factors significantly affecting survival included five or more bone metastases than less(P=0.0080),and treatment with chemotherapy(P<0.001),bone modifying agents(P=0.0175)and immune checkpoint inhibitors(P=0.0128).In recent years,advances in various treatment methods have extended the survival period for patients with advanced cancer.It is necessary not only to simply extend survival time,but also to maintain ADL and improve QOL.CONCLUSION Various therapeutic interventions including surgical approach for bone metastasis,which is a disorder of locomotor organs,are increasingly required.Guidelines and scoring system for prognosis need to be revised promptly.展开更多
IBM Tivoli Risk Manger与Check Point Next Generation相集成,产品交叉认证以实现无缝互操作性。互联网安全领域的全球领先厂商——Check Point软件技术有限公司日前宣布,它将通过更紧密地集成Check Point Next Generation安全解决方案...IBM Tivoli Risk Manger与Check Point Next Generation相集成,产品交叉认证以实现无缝互操作性。互联网安全领域的全球领先厂商——Check Point软件技术有限公司日前宣布,它将通过更紧密地集成Check Point Next Generation安全解决方案和IBM的自动化安全管理软件。展开更多
Latent membrane protein 1 （LMP1）, an important protein encoded by Epstein Barr virus （EBV）, has been implied to link with the pathogenesis of nasopharyngeal carcinoma （NPC）. Its dual effects of increasing cell p...Latent membrane protein 1 （LMP1）, an important protein encoded by Epstein Barr virus （EBV）, has been implied to link with the pathogenesis of nasopharyngeal carcinoma （NPC）. Its dual effects of increasing cell proliferation and inhibiting cell apoptosis have been confirmed. In this study, we showed that the expression of Survivin and CDK4 protein in CNE-LMP1, a LMP1 positive NPC epithelial cell line, is higher than in LMP1 negative NPC epithelial cell line- CNE1, and the expression is LMP1 dosage-dependent. Although it was reported that Survivin specifically expressed in cell cycle G2/M phase, our studies suggested that LMP1 could promote the expression of Survivin in G0/G1, S and G2/ M phase. It also showed that Survivin and CDK4 could be accumulated more in the nuclei triggered by LMP1. More interestingly, Survivin and CDK4 could form a protein complex in the nuclei of CNE-LMP1 rather than in that of CNE1, which demonstrated that the interaction between these two proteins could be promoted by LMPI. These results strongly suggested that the role of LMP1 in the regulation of Survivin and CDK4 may also shed some light on the mechanism research of LMP1 in NPC.展开更多
Systemic sclerosis(SSc)is a rare connective tissue disorder.It is a chronic multisystem disease characterized by vascular dysfunction and progressive fibrosis of tissue,with skin hardening and thickening(known as scle...Systemic sclerosis(SSc)is a rare connective tissue disorder.It is a chronic multisystem disease characterized by vascular dysfunction and progressive fibrosis of tissue,with skin hardening and thickening(known as scleroderma)being the hallmark of the disease.It tends to affect females more than males and has a higher prevalence in African American population with earlier onset and more severe disease.While scleroderma can be a manifestation of conditions other than SSC,the presence of skin thickening of the fingers,extending proximally to metacarpophalangeal joints is sufficient to classify a patient as having SSc.SSc treatment is challenging given the heterogeneity of the disease,multiple organ involvement,different subtypes and poorly understood etiology and pathogenesis.Yet,systemic immunosuppressive therapy is often the treatment of choice.Here we present a 60-year-old white female who developed skin thickening of her fingers extending to the forearms and of her proximal thighs after being treated with pembrolizumab for metastatic non-small cell lung cancer.It was difficult to determine internal organ involvement given her history of metastatic lung cancer,but scleroderma specific autoantibodies were negative.Her symptoms improved after treatment with methotrexate and stopping pembrolizumab.This is one of the first case reports of scleroderma secondary to pembrolizumab.展开更多
In this work, the most detrimental missense mutations of Madl protein that cause various types of cancer were identified computationally and the substrate binding efficiencies of those missense mutations were analyzed...In this work, the most detrimental missense mutations of Madl protein that cause various types of cancer were identified computationally and the substrate binding efficiencies of those missense mutations were analyzed. Out of 13 missense mutations, I Mutant 2.0, SIFT and PolyPhen programs identified 3 variants that were less stable, deleterious and damaging respectively. Subsequently, modeling of these 3 variants was performed to understand the change in their conformations with respect to the native Madl by computing their root mean squared deviation （RMSD）. Furthermore, the native protein and the 3 mutants were docked with the binding partner Mad2 to explain the substrate binding efficiencies of those detrimental missense mutations. The docking studies identified that all the 3 mutants caused lower binding affinity for Mad2 than the native protein. Finally, normal mode analysis determined that the loss of binding affinity of these 3 mutants was caused by altered flexibility in the amino acids that bind to Mad2 compared with the native protein. Thus, the present study showed that majority of the substrate binding amino acids in those 3 mutants displayed loss of flexibility, which could be the theoretical explanation of decreased binding affinity between the mutant Madl and Mad2.展开更多
In terms of global cancer-related deaths,hepatocellular carcinoma (HCC) has the fourth highest mortality rate.Up until 2017,treatment of advanced HCC was largely limited to sorafenib,an oral tyrosine kinase inhibitor,...In terms of global cancer-related deaths,hepatocellular carcinoma (HCC) has the fourth highest mortality rate.Up until 2017,treatment of advanced HCC was largely limited to sorafenib,an oral tyrosine kinase inhibitor,with little to no success in the development of alternative treatment options.However,in the past two years,there has been an unprecedented increase in both the number and type of treatment options available for HCC.As of 2019,the US FDA has approved four oral tyrosine kinase inhibitors,two immune checkpoint inhibitors,and one anti-angiogenesis antibody for the treatment of HCC.Even with this new variety,systemic treatment of advanced HCC remains largely unsatisfactory,and the median survival rate stands at approximately one year.The expected breakthrough of using immune checkpoint inhibitors in advanced HCC did not materialize in 2019.The use of immune checkpoint inhibitors in conjunction with oral tyrosine kinase inhibitors or antiangiogenesis medications is the current clinical research trend,the results of which are eagerly anticipated.Despite limited progress in survival,HCC research is currently experiencing a period of growth and innovation,and there is hope for significant advances in the treatment of advanced HCC as the field continues to develop.展开更多
In this review,we will highlight the importance of cancer germline antigen-specific cytotoxic CD8^(+) T lymphocytes(CTL)and the factors affecting antitumor CTL responses.In light of cancer immunotherapy,we will emphas...In this review,we will highlight the importance of cancer germline antigen-specific cytotoxic CD8^(+) T lymphocytes(CTL)and the factors affecting antitumor CTL responses.In light of cancer immunotherapy,we will emphasis the need to further understand the features,characteristics,and actions of modulatory receptors of human cancer germline-specific CTLs,in order to determine the optimal conditions for antitumor CTL responses.展开更多
Circulating tumor cells(CTCs)have received a lot of attention as a novel biomarker for cancer research in past decades.CTCs infiltrate the bloodstream derived from the primary tumor,and are significantly involved in c...Circulating tumor cells(CTCs)have received a lot of attention as a novel biomarker for cancer research in past decades.CTCs infiltrate the bloodstream derived from the primary tumor,and are significantly involved in cancer metastasis and recurrence.Although clinical applications have been challenging owing to the difficulties of CTC identification,recent development of technology for specific enrichment and detection of CTCs contributes to diagnosis and treatment.Furthermore,CTC analyses will shed new light on the biological mechanisms of cancer progression and metastasis.A number of clinical studies have already been carried out on the basis of CTC technology.Nevertheless,the clinical utility of CTCs is still unknown in gastric cancer.In this review,we elaborate on the latest advances of CTC research in gastric cancer.展开更多
文摘BACKGROUND Bone metastasis has various negative impacts.Activities of daily living(ADL)and quality of life(QOL)can be significantly decreased,survival may be impacted,and medical expenses may increase.It is estimated that at least 5%cancer patients might be suffering from bone metastases.In 2016,we published the Comprehensive Guidelines for the Diagnosis and Treatment of Bone Metastasis.Since then,the therapeutic outcomes for patients have gradually improved.As life expectancy is a major determinant of surgical intervention,the strategy should be modified if the prolongation of survival is to be achieved.AIM To monitor how bone metastasis treatment has changed before and after launch of our guidelines for bone metastasis.METHODS For advanced cancer patients with bone metastasis who visited the Department of Clinical Oncology at Akita University hospital between 2012 and 2023,parameters including the site and number of bone metastases,laboratory data,and survival time,were extracted from electronic medical records and the Katagiri score was calculated.The association with survival was determined for each factor.RESULTS Data from 136 patients were obtained.The 1-year survival rate for the poor prognosis group with a higher Katagiri score was 20.0%in this study,which was 6%and an apparent improvement from 2014 when the scoring system was developed.Other factors significantly affecting survival included five or more bone metastases than less(P=0.0080),and treatment with chemotherapy(P<0.001),bone modifying agents(P=0.0175)and immune checkpoint inhibitors(P=0.0128).In recent years,advances in various treatment methods have extended the survival period for patients with advanced cancer.It is necessary not only to simply extend survival time,but also to maintain ADL and improve QOL.CONCLUSION Various therapeutic interventions including surgical approach for bone metastasis,which is a disorder of locomotor organs,are increasingly required.Guidelines and scoring system for prognosis need to be revised promptly.
文摘IBM Tivoli Risk Manger与Check Point Next Generation相集成,产品交叉认证以实现无缝互操作性。互联网安全领域的全球领先厂商——Check Point软件技术有限公司日前宣布,它将通过更紧密地集成Check Point Next Generation安全解决方案和IBM的自动化安全管理软件。
基金National Nature Science Foundation for Distinguished Young Scholar of China (No.39525022)National Basic Research Program(No.2004CB518703) National Nature Science Foundation of China (No.30570085).
文摘Latent membrane protein 1 （LMP1）, an important protein encoded by Epstein Barr virus （EBV）, has been implied to link with the pathogenesis of nasopharyngeal carcinoma （NPC）. Its dual effects of increasing cell proliferation and inhibiting cell apoptosis have been confirmed. In this study, we showed that the expression of Survivin and CDK4 protein in CNE-LMP1, a LMP1 positive NPC epithelial cell line, is higher than in LMP1 negative NPC epithelial cell line- CNE1, and the expression is LMP1 dosage-dependent. Although it was reported that Survivin specifically expressed in cell cycle G2/M phase, our studies suggested that LMP1 could promote the expression of Survivin in G0/G1, S and G2/ M phase. It also showed that Survivin and CDK4 could be accumulated more in the nuclei triggered by LMP1. More interestingly, Survivin and CDK4 could form a protein complex in the nuclei of CNE-LMP1 rather than in that of CNE1, which demonstrated that the interaction between these two proteins could be promoted by LMPI. These results strongly suggested that the role of LMP1 in the regulation of Survivin and CDK4 may also shed some light on the mechanism research of LMP1 in NPC.
文摘Systemic sclerosis(SSc)is a rare connective tissue disorder.It is a chronic multisystem disease characterized by vascular dysfunction and progressive fibrosis of tissue,with skin hardening and thickening(known as scleroderma)being the hallmark of the disease.It tends to affect females more than males and has a higher prevalence in African American population with earlier onset and more severe disease.While scleroderma can be a manifestation of conditions other than SSC,the presence of skin thickening of the fingers,extending proximally to metacarpophalangeal joints is sufficient to classify a patient as having SSc.SSc treatment is challenging given the heterogeneity of the disease,multiple organ involvement,different subtypes and poorly understood etiology and pathogenesis.Yet,systemic immunosuppressive therapy is often the treatment of choice.Here we present a 60-year-old white female who developed skin thickening of her fingers extending to the forearms and of her proximal thighs after being treated with pembrolizumab for metastatic non-small cell lung cancer.It was difficult to determine internal organ involvement given her history of metastatic lung cancer,but scleroderma specific autoantibodies were negative.Her symptoms improved after treatment with methotrexate and stopping pembrolizumab.This is one of the first case reports of scleroderma secondary to pembrolizumab.
文摘In this work, the most detrimental missense mutations of Madl protein that cause various types of cancer were identified computationally and the substrate binding efficiencies of those missense mutations were analyzed. Out of 13 missense mutations, I Mutant 2.0, SIFT and PolyPhen programs identified 3 variants that were less stable, deleterious and damaging respectively. Subsequently, modeling of these 3 variants was performed to understand the change in their conformations with respect to the native Madl by computing their root mean squared deviation （RMSD）. Furthermore, the native protein and the 3 mutants were docked with the binding partner Mad2 to explain the substrate binding efficiencies of those detrimental missense mutations. The docking studies identified that all the 3 mutants caused lower binding affinity for Mad2 than the native protein. Finally, normal mode analysis determined that the loss of binding affinity of these 3 mutants was caused by altered flexibility in the amino acids that bind to Mad2 compared with the native protein. Thus, the present study showed that majority of the substrate binding amino acids in those 3 mutants displayed loss of flexibility, which could be the theoretical explanation of decreased binding affinity between the mutant Madl and Mad2.
文摘In terms of global cancer-related deaths,hepatocellular carcinoma (HCC) has the fourth highest mortality rate.Up until 2017,treatment of advanced HCC was largely limited to sorafenib,an oral tyrosine kinase inhibitor,with little to no success in the development of alternative treatment options.However,in the past two years,there has been an unprecedented increase in both the number and type of treatment options available for HCC.As of 2019,the US FDA has approved four oral tyrosine kinase inhibitors,two immune checkpoint inhibitors,and one anti-angiogenesis antibody for the treatment of HCC.Even with this new variety,systemic treatment of advanced HCC remains largely unsatisfactory,and the median survival rate stands at approximately one year.The expected breakthrough of using immune checkpoint inhibitors in advanced HCC did not materialize in 2019.The use of immune checkpoint inhibitors in conjunction with oral tyrosine kinase inhibitors or antiangiogenesis medications is the current clinical research trend,the results of which are eagerly anticipated.Despite limited progress in survival,HCC research is currently experiencing a period of growth and innovation,and there is hope for significant advances in the treatment of advanced HCC as the field continues to develop.
基金This work was supported by Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(CIFMS),China(grant number:2018-I2M-2-002)MRC Human Immunology Unit Core and Nuffield Department of Medicine,Oxford University.Illustrations were created with BioRender(Biorender.com)。
文摘In this review,we will highlight the importance of cancer germline antigen-specific cytotoxic CD8^(+) T lymphocytes(CTL)and the factors affecting antitumor CTL responses.In light of cancer immunotherapy,we will emphasis the need to further understand the features,characteristics,and actions of modulatory receptors of human cancer germline-specific CTLs,in order to determine the optimal conditions for antitumor CTL responses.
文摘Circulating tumor cells(CTCs)have received a lot of attention as a novel biomarker for cancer research in past decades.CTCs infiltrate the bloodstream derived from the primary tumor,and are significantly involved in cancer metastasis and recurrence.Although clinical applications have been challenging owing to the difficulties of CTC identification,recent development of technology for specific enrichment and detection of CTCs contributes to diagnosis and treatment.Furthermore,CTC analyses will shed new light on the biological mechanisms of cancer progression and metastasis.A number of clinical studies have already been carried out on the basis of CTC technology.Nevertheless,the clinical utility of CTCs is still unknown in gastric cancer.In this review,we elaborate on the latest advances of CTC research in gastric cancer.
