Some interferon beta (IFNβ)-treated patients with multiple sclerosis develop antibody-mediated decreased bioactivity with resultant loss of therapeutic effect. The authors developed realtime multiplex reverse transcr...Some interferon beta (IFNβ)-treated patients with multiple sclerosis develop antibody-mediated decreased bioactivity with resultant loss of therapeutic effect. The authors developed realtime multiplex reverse transcriptase PCR to measure expression of three IFNβ-inducible genes to directly assess IFNβbioactivity in patients with neutralizing antibodies (NAbs). The three genes responded in tandem. Correlation of NAb level with bioactivity at low/ moderate NAb levels was poor, indicating that for such patients, direct measurement of IFNβbioactivity is most reliable.展开更多
Objective: To determine the time course of brain atrophy during treatment with once- weekly IM interferon β - 1a (IFNβ - 1a). Methods: The MRI cohort (n = 386) of the European IFNβ - 1a dose comparison study in rel...Objective: To determine the time course of brain atrophy during treatment with once- weekly IM interferon β - 1a (IFNβ - 1a). Methods: The MRI cohort (n = 386) of the European IFNβ - 1a dose comparison study in relapsing multiple sclerosis (MS)- was analyzed. In addition to baseline and three annual scans, a frequent subgroup (n = 138) had two scans before treatment initiation and scans at months 4, 5, 6, 10, and 11. Brain parenchymal fraction (BPF), a normalized measure of whole- brain atrophy, and volume of Gd- enhancing lesions (T1Gd) and T2 hyperintense lesions (T2LL) were evaluated. Results: BPF decrease was - 0.686% (first year), - 0.377% (second year), and - 0.378% (third year). Analysis of the frequent subgroup showed that 68% of the first- year BPF decrease occurred during the first 4 months of treatment. This change was paralleled by a drop in T1Gd and T2LL. In the frequent subgroup, an annualized atrophy rate was determined by a regression slope for the pretreatment period and from month 4 of treatment onward. Annualized pretreatment rate (- 1.06% ) was significantly higher than the under- treatment rate (- 0.33% ). Conclusions: In the first year of treatment with anti- inflammatory agents, atrophy measurements are possibly confounded by resolution of inflammatory edema or more remote effects of previous damage to the CNS. The atrophy rate reduction observed after treatment month 4 may reflect a beneficial but partial effect of interferon β - 1a and was sustained over the 3- year study period.展开更多
Objective: To compare the efficacy of acetaminophen, ibuprofen, and prednisone in the treatment of interferon β-1a (IFNβ-1a) flu like syndrome (FLS). Methods: Patients with relapsing remitting multiple sclerosis ini...Objective: To compare the efficacy of acetaminophen, ibuprofen, and prednisone in the treatment of interferon β-1a (IFNβ-1a) flu like syndrome (FLS). Methods: Patients with relapsing remitting multiple sclerosis initiating treatment with IM IFNβ 1a were randomized in a multicenter, randomized, double blind, controlled trial to receive acetaminophen 500 mg before and 6 and 12 hours after each injection, ibuprofen 400 mg before and 6 and 12 hours after each injection, or prednisone 60 mg daily for 1 week, plus tapering. Patients were instructed to keep a daily diary of fever severity, myalgia, chills, headache, and asthenia for 27 days. The sum of the scores of individual symptoms was used to obtain a daily FLS index. The primary outcome was the FLS index area under the curve (AUC) corrected by the number of measurement days. Results: Eighty four patients were randomized at 11 hospitals: acetaminophen (n = 28), ibuprofen (n = 28), and corticosteroids (n = 28). No differences were detected between treatments in the mean AUC of the FLS index. With limitation of the analysis to the days of IM IFNβ 1a injection, differences favoring ibuprofen were observed in the mean FLS index (p = 0.0007). Conclusions: No prophylactic treatment for flu like syndrome seems to be superior to another in terms of overall well being during the first month of IM IFNβ 1a therapy. However, ibuprofen confers better control of symptoms immediately following IM IFNβ 1a injection.展开更多
Objective: Cancer immunotherapy has made remarkable advances in recent years, but its effectiveness in treating gastric cancer is often limited by the complexity of the tumor microenvironment and the lack of effective...Objective: Cancer immunotherapy has made remarkable advances in recent years, but its effectiveness in treating gastric cancer is often limited by the complexity of the tumor microenvironment and the lack of effective biomarkers. This study aimed to identify effective biomarkers for immunotherapy treatment by characterizing the tumor microenvironment.Methods: We retrieved the RNA-seq data from gastric cancer patients treated with the programmed death 1(PD-1) blockade pembrolizumab. Differentially expressed genes associated with clinical outcomes were identified and further analyzed using gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis. Gene signature scores were calculated by single sample Gene Set Enrichment Analysis(ssGSEA). The infiltration levels of immune cells were quantified using the xCell website. Cell type enrichment analysis was performed to compare treatment response and non-response groups, and regression analysis was used to investigate the relationship between interferon gamma(IFNγ) immune response and immune cell infiltration. Biomarkers were identified using least absolute shrinkage and selection operator(LASSO) analysis.Results: Compared to normal tissues, cytokine activity and interleukin-6 production were highly activated in gastric tumors. Responders to pembrolizumab showed significantly up-regulated expression of IFNγ responserelated genes. Cell type enrichment analysis revealed that Th1 cells were significantly enriched in the tumor microenvironment of responders. Regression analysis indicated that Th1 cells induced IFNγ response more efficiently than other cell types. Using signatures of Th1 cells, stromal cells and IFNγ response, a set of eight genes were identified that effectively predicted the efficacy of immunotherapy treatment and patient prognosis.Conclusions: Th1 cells promote therapeutic efficacy of PD-1 blockade by promoting IFNγ immune response in gastric cancer. The identified biomarkers have the potential to improve the effectiveness of immunotherapy treatment for gastric cancer patients.展开更多
文摘Some interferon beta (IFNβ)-treated patients with multiple sclerosis develop antibody-mediated decreased bioactivity with resultant loss of therapeutic effect. The authors developed realtime multiplex reverse transcriptase PCR to measure expression of three IFNβ-inducible genes to directly assess IFNβbioactivity in patients with neutralizing antibodies (NAbs). The three genes responded in tandem. Correlation of NAb level with bioactivity at low/ moderate NAb levels was poor, indicating that for such patients, direct measurement of IFNβbioactivity is most reliable.
文摘Objective: To determine the time course of brain atrophy during treatment with once- weekly IM interferon β - 1a (IFNβ - 1a). Methods: The MRI cohort (n = 386) of the European IFNβ - 1a dose comparison study in relapsing multiple sclerosis (MS)- was analyzed. In addition to baseline and three annual scans, a frequent subgroup (n = 138) had two scans before treatment initiation and scans at months 4, 5, 6, 10, and 11. Brain parenchymal fraction (BPF), a normalized measure of whole- brain atrophy, and volume of Gd- enhancing lesions (T1Gd) and T2 hyperintense lesions (T2LL) were evaluated. Results: BPF decrease was - 0.686% (first year), - 0.377% (second year), and - 0.378% (third year). Analysis of the frequent subgroup showed that 68% of the first- year BPF decrease occurred during the first 4 months of treatment. This change was paralleled by a drop in T1Gd and T2LL. In the frequent subgroup, an annualized atrophy rate was determined by a regression slope for the pretreatment period and from month 4 of treatment onward. Annualized pretreatment rate (- 1.06% ) was significantly higher than the under- treatment rate (- 0.33% ). Conclusions: In the first year of treatment with anti- inflammatory agents, atrophy measurements are possibly confounded by resolution of inflammatory edema or more remote effects of previous damage to the CNS. The atrophy rate reduction observed after treatment month 4 may reflect a beneficial but partial effect of interferon β - 1a and was sustained over the 3- year study period.
文摘Objective: To compare the efficacy of acetaminophen, ibuprofen, and prednisone in the treatment of interferon β-1a (IFNβ-1a) flu like syndrome (FLS). Methods: Patients with relapsing remitting multiple sclerosis initiating treatment with IM IFNβ 1a were randomized in a multicenter, randomized, double blind, controlled trial to receive acetaminophen 500 mg before and 6 and 12 hours after each injection, ibuprofen 400 mg before and 6 and 12 hours after each injection, or prednisone 60 mg daily for 1 week, plus tapering. Patients were instructed to keep a daily diary of fever severity, myalgia, chills, headache, and asthenia for 27 days. The sum of the scores of individual symptoms was used to obtain a daily FLS index. The primary outcome was the FLS index area under the curve (AUC) corrected by the number of measurement days. Results: Eighty four patients were randomized at 11 hospitals: acetaminophen (n = 28), ibuprofen (n = 28), and corticosteroids (n = 28). No differences were detected between treatments in the mean AUC of the FLS index. With limitation of the analysis to the days of IM IFNβ 1a injection, differences favoring ibuprofen were observed in the mean FLS index (p = 0.0007). Conclusions: No prophylactic treatment for flu like syndrome seems to be superior to another in terms of overall well being during the first month of IM IFNβ 1a therapy. However, ibuprofen confers better control of symptoms immediately following IM IFNβ 1a injection.
基金financially supported by the National Natural Science Foundation of China (No. 82030079, 82341005, 81972656 and 82173035)the National Science and Technology Major Project of China (No. 2022YFC3400 901)Sino-Russian Math Center in PKU。
文摘Objective: Cancer immunotherapy has made remarkable advances in recent years, but its effectiveness in treating gastric cancer is often limited by the complexity of the tumor microenvironment and the lack of effective biomarkers. This study aimed to identify effective biomarkers for immunotherapy treatment by characterizing the tumor microenvironment.Methods: We retrieved the RNA-seq data from gastric cancer patients treated with the programmed death 1(PD-1) blockade pembrolizumab. Differentially expressed genes associated with clinical outcomes were identified and further analyzed using gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis. Gene signature scores were calculated by single sample Gene Set Enrichment Analysis(ssGSEA). The infiltration levels of immune cells were quantified using the xCell website. Cell type enrichment analysis was performed to compare treatment response and non-response groups, and regression analysis was used to investigate the relationship between interferon gamma(IFNγ) immune response and immune cell infiltration. Biomarkers were identified using least absolute shrinkage and selection operator(LASSO) analysis.Results: Compared to normal tissues, cytokine activity and interleukin-6 production were highly activated in gastric tumors. Responders to pembrolizumab showed significantly up-regulated expression of IFNγ responserelated genes. Cell type enrichment analysis revealed that Th1 cells were significantly enriched in the tumor microenvironment of responders. Regression analysis indicated that Th1 cells induced IFNγ response more efficiently than other cell types. Using signatures of Th1 cells, stromal cells and IFNγ response, a set of eight genes were identified that effectively predicted the efficacy of immunotherapy treatment and patient prognosis.Conclusions: Th1 cells promote therapeutic efficacy of PD-1 blockade by promoting IFNγ immune response in gastric cancer. The identified biomarkers have the potential to improve the effectiveness of immunotherapy treatment for gastric cancer patients.
