Objective To study the expression and interactions of DNA methyltransferase 1 (DNMT1),enhancer of zeste homolog 2 (EZH2) and histone deacetylase 1 (HDAC1) in gastric cancer cell lines and tissue specimens.Methods The expression of DNMT1,EZH2 and HDAC1 was detected at mRNA and protein level in gastric cancer lines MKN28,SGC7901,BGC823,AGS,normal gastric epithelium cell line GES-1 and 10 pairs of fresh gastric cancer tissues and corresponding normal gastric tissues by real-time polymerase chain reaction and Western blot.Whether DNMT1,EZH2 and HDAC1 forming complex or not was detected by co-immunoprecipitation (Co-IP) in well-differentiated gastric cancer cell line MKN28,medium-differentiated gastric cancer cell line SGC7901,lowdifferentiated gastric cancer cell line BCG823,normal gastric epithelium cell line GES-1,mediumdifferentiated,medium to low-differentiated,low-differentiated gastric cancer tissues and corresponding normal gastric tissues.Results Compared with that of normal gastric epithelium cell and gastric tissue,the expression of DNMT1,EZH2 and HDAC1 in gastric cancer cell lines and gastric tissue was higher.The results of Co-IP indicated that DNMT1,EZH2 and HDAC1 formed complex in the high,medium,and poor differentiated gastric cancer cells and the medium,mediumlow,poor differentiated gastric cancer tissues,but not in normal gastric epithelium cell and tissue.Conclusion DNMT1,EZH2 and HDAC1 highly expressed in gastric cancer and there was interaction effects among them,which might be an important mechanism in the correlation between DNA methylation and histone modifications in gastric cancer.

Objective: Mirvetuximab soravtansine (MIRV), a new antibody-drug conjugate, versus the investigator’s choice of chemotherapy (IC) was the first treatment to demonstrate benefits for progression-free and overall survival in platinum-resistant recurrent ovarian cancer (PROC) with high folate receptor-alpha (high-FRα) expression. Efficacy, safety, and economic effectiveness make MIRV the new standard of care for these patients. Methods: Based on patients and clinical parameters from MIRASOL (GOG 3045/ENGOTov55) phase III randomized controlled trials, the Markov model with a 20-year time horizon was established to evaluate the cost and efficacy of MIRV and IC for PROC with high-FRα expression, considering the bevacizumab-pretreated situation from the American healthcare system. Total cost, life-years (LYs), quality-adjusted life-years (QALYs), incremental costeffectiveness ratio (ICER), and incremental net health benefits were the main outcome indicators and compared with willingness-to-pay threshold of $100,000/QALY. Sensitivity and scenario analyses were conducted. Results: Compared with the IC, MIRV was associated with incremental costs of $538,251, $575,674, and $188,248 with the corresponding QALYs (LYs) increased by 0.90 (1.55), 1.09 (1.88), and 0.53 (0.79), leading to ICERs of $596,189/QALY ($347,995/LY), $530,061/QALY ($306,894/LY), and $1,011,310/QALY ($680,025/LY) in the overall, bevacizumab-naïve, and bevacizumab-pretreated patients, respectively. When MIRV is reduced by more than 75%, it may be a cost-effective treatment. Conclusion At the current price, MIRV for PROC with high-FRα expression is not the cost-effective strategy in the US. However, its treatment has higher health benefits in bevacizumab-naïve patients, which is likely to be an alternative.

Objective: Mirvetuximab soravtansine (MIRV), a new antibody-drug conjugate, versus the investigator’s choice of chemotherapy (IC) was the first treatment to demonstrate benefits for progression-free and overall survival in platinum-resistant recurrent ovarian cancer (PROC) with high folate receptor-alpha (high-FRα) expression. Efficacy, safety, and economic effectiveness make MIRV the new standard of care for these patients. Methods: Based on patients and clinical parameters from MIRASOL (GOG 3045/ENGOTov55) phase III randomized controlled trials, the Markov model with a 20-year time horizon was established to evaluate the cost and efficacy of MIRV and IC for PROC with high-FRα expression, considering the bevacizumab-pretreated situation from the American healthcare system. Total cost, life-years (LYs), quality-adjusted life-years (QALYs), incremental costeffectiveness ratio (ICER), and incremental net health benefits were the main outcome indicators and compared with willingness-to-pay threshold of $100,000/QALY. Sensitivity and scenario analyses were conducted. Results: Compared with the IC, MIRV was associated with incremental costs of $538,251, $575,674, and $188,248 with the corresponding QALYs (LYs) increased by 0.90 (1.55), 1.09 (1.88), and 0.53 (0.79), leading to ICERs of $596,189/QALY ($347,995/LY), $530,061/QALY ($306,894/LY), and $1,011,310/QALY ($680,025/LY) in the overall, bevacizumab-naïve, and bevacizumab-pretreated patients, respectively. When MIRV is reduced by more than 75%, it may be a cost-effective treatment. Conclusion At the current price, MIRV for PROC with high-FRα expression is not the cost-effective strategy in the US. However, its treatment has higher health benefits in bevacizumab-naïve patients, which is likely to be an alternative.

Objective: Mirvetuximab soravtansine (MIRV), a new antibody-drug conjugate, versus the investigator’s choice of chemotherapy (IC) was the first treatment to demonstrate benefits for progression-free and overall survival in platinum-resistant recurrent ovarian cancer (PROC) with high folate receptor-alpha (high-FRα) expression. Efficacy, safety, and economic effectiveness make MIRV the new standard of care for these patients. Methods: Based on patients and clinical parameters from MIRASOL (GOG 3045/ENGOTov55) phase III randomized controlled trials, the Markov model with a 20-year time horizon was established to evaluate the cost and efficacy of MIRV and IC for PROC with high-FRα expression, considering the bevacizumab-pretreated situation from the American healthcare system. Total cost, life-years (LYs), quality-adjusted life-years (QALYs), incremental costeffectiveness ratio (ICER), and incremental net health benefits were the main outcome indicators and compared with willingness-to-pay threshold of $100,000/QALY. Sensitivity and scenario analyses were conducted. Results: Compared with the IC, MIRV was associated with incremental costs of $538,251, $575,674, and $188,248 with the corresponding QALYs (LYs) increased by 0.90 (1.55), 1.09 (1.88), and 0.53 (0.79), leading to ICERs of $596,189/QALY ($347,995/LY), $530,061/QALY ($306,894/LY), and $1,011,310/QALY ($680,025/LY) in the overall, bevacizumab-naïve, and bevacizumab-pretreated patients, respectively. When MIRV is reduced by more than 75%, it may be a cost-effective treatment. Conclusion At the current price, MIRV for PROC with high-FRα expression is not the cost-effective strategy in the US. However, its treatment has higher health benefits in bevacizumab-naïve patients, which is likely to be an alternative.

BACKGROUND AND PURPOSE: Encephalitis caused by Listeria monocytogenes (L. monocytogenes) is rare but sometimes fatal. Early diagnosis is difficult using routine cerebrospinal fluid (CSF) tests, while next-generation sequencing (NGS) is increasingly being used for the detection and characterization of pathogens. METHODS: This study set up and applied unbiased NGS to detect L. monocytogenes in CSF collected from three cases of clinically suspected listeria meningoencephalitis. RESULTS: Three cases of patients with acute/subacute meningoencephalitis are reported. Magnetic resonance imaging and blood cultures led to a suspected diagnosis of L. monocytogenes, while the CSF cultures were negative. Unbiased NGS of CSF identified and sequenced reads corresponding to L. monocytogenes in all three cases. CONCLUSIONS: This is the first report highlighting the feasibility of applying NGS of CSF as a diagnostic method for central nervous system (CNS) L. monocytogenes infection. Routine application of this technology in clinical microbiology will significantly improve diagnostic methods for CNS infectious diseases.
Central Nervous System ; Cerebrospinal Fluid ; Communicable Diseases ; Diagnosis ; Early Diagnosis ; Encephalitis ; Humans ; Listeria monocytogenes* ; Listeria* ; Magnetic Resonance Imaging ; Meningitis, Listeria ; Meningoencephalitis* ; Methods