Inrecentyearsmanytargetedagentstreatinggastriccancerhavebeenevaluatedinclinical studies.Trastuzumab,an anti-HER-2 monoclonal antibody,has shown activity against HER-2-positive gastric cancer and become the first targeted agent approved in gastric cancer.Drugs targeting epidermal growth factor receptor,including monoclonal antibody and tyrosine kinase inhibitor,bring survival benefit to patients with gastric cancer.Addi tionally,vascular endothelial growth factor inhibitors are also under investigation.Other targeted agents are in preclinical or early clinical development,such as m-TOR inhibitors and c-MET inhibi-tors.

Objective:To explore the clinical effect of azacitidine combined with CAG regimen on the treatment of relapsed/refractory acute myeloid leukemia (AML).Methods:The data of 50 patients with relapsed/refractory AML (non-acute promyelocytic leukemia) in Jining No. 1 People's Hospital from September 2018 to September 2019 was retrospectively analyzed, and the patients were divided into the control group and the test group according to the different treatment drugs. The control group (28 cases) was treated with CAG regimen alone, and the test group (22 cases) was treated with azacitidine combined with CAG regimen. The total effective rate and adverse reactions of the two groups were observed after 1 course of treatment.Results:After one course of treatment, the total clinical effective rate in the test group was 86% (19/22), and the rate in the control group was 71% (20/28), there was a statistically significant difference between the two groups (χ 2 = 5.273, P < 0.05). There were no significant differences in the incidence of adverse reactions such as fever, pulmonary infection, vomiting, and thrombocytopenia between the two groups (all P > 0.05). Conclusion:Azacitidine combined with CAG regimen in the treatment of relapsed/refractory AML can improve the clinical efficacy without increasing the adverse reactions.

Objective:To investigate the effect of chidamide combined with arsenic acid on the proliferation inhibitory of T cell lymphoma Hut-78 cells and its mechanism.Methods:Low concentration group included 1.0 μmol/L chidamide, 4.0 μmol/L arsenic trioxide or both of them (1.0 μmol/L chidamide + 4.0 μmol/L arsenic trioxide). High concentration group included 1.5 μmol/L chidamide, 6.0 μmol/L arsenic trioxide or both of them (1.5 μmol/L chidamide + 6.0 μmol/L arsenic trioxide). Both groups were used to treat Hut-78 cells for 24 h and 48 h, respectively. Cell proliferation of Hut-78 cells in all drug treatment groups was tested by using methyl thiazolyl tetrazolium (MTT) method, and the proliferation inhibitory rate was also calculated. The expressions of vascular endothelial growth factor (VEGR) and bcl-2 protein of Hut-78 cells in different drug treatment groups by using Western blotting.Results:The cell proliferation inhibitory rate of Hut-78 cells treated for 24 h of 1.0 μmol/L chidamide, 4.0 μmol/L arsenic trioxide or both of them (1.0 μmol/L chidamide+ 4.0 μmol/L arsenic trioxide) was (8.8±0.1)%, (9.2±0.5)% and (11.0±0.1)%, respectively ( F = 12.45, P < 0.05); The cell proliferation inhibitory rate of Hut-78 cells treated for 48 h was (19.1±0.5)%, (18.3±0.9)%, (23.1±1.3)%, respectively ( F = 9.86, P < 0.05). The cell proliferation inhibitory rate of Hut-78 cells treated for 24 h of 1.5 μmol/L chidamide, 6.0 μmol/L arsenic trioxide or both of them (1.5 μmol/L chidamide+ 6.0 μmol/L arsenic trioxide) was (15.4±0.9)%, (13.2±0.9)% and (18.2±1.1)%, respectively ( F = 7.06, P < 0.05); The cell proliferation inhibitory rate of Hut-78 cells treated for 48 h was (28.5±1.2)%, (31.3±0.8)%, (45.2±2.1)%, respectively ( F = 14.32, P < 0.05). When Hut-78 cells were treated with 1.0 μmol/L chidamide, 4.0 μmol/L arsenic trioxide or both of them (1.0 μmol/L chidamide+ 4.0 μmol/L arsenic trioxide) for 24 h, the relative expression level of bcl-2 protein was (58.4±2.9)%, (55.9±3.8)%, (53.2±2.1)%, respectively ( F = 17.52, P < 0.05); the relative expression level of VEGF protein was (60.5±4.2)%, (57.5±2.8)%, (50.9±3.5)%, respectively ( F = 7.36, P < 0.05). When Hut-78 cells were treated with 1.0 μmol/L chidamide, 4.0 μmol/L arsenic trioxide or both of them (1.0 μmol/L chidamide+ 4.0 μmol/L arsenic trioxide) for 48 h, the relative expression level of bcl-2 protein was (48.2±1.8)%, (40.1±2.2)%, (32.3±3.1)%, respectively ( F = 10.38, P < 0.05); the relative expression level of VEGF protein was (51.4±4.1)%, (48.9±2.9)%, (40.8±3.8)%, respectively ( F = 8.96, P < 0.05). When Hut-78 cells were treated with 1.5 μmol/L chidamide, 6.0 μmol/L arsenic trioxide or both of them (1.5 μmol/L chidamide+ 6.0 μmol/L arsenic trioxide) for 24 h, the relative expression level of bcl-2 protein was (55.4±3.1)%, (42.5±2.8)%, (37.8±4.2)%, respectively ( F= 10.35, P < 0.05); the relative expression level of VEGF protein was (49.2±3.4)%, (42.1±4.9)%, (34.3±5.1)%, respectively ( F= 17.82, P <0.05). When Hut-78 cells were treated with 1.5 μmol/L chidamide, 6.0 μmol/L arsenic trioxide or both of them (1.5 μmol/L chidamide+ 6.0 μmol/L arsenic trioxide) for 48 h, the relative expression level of bcl-2 protein was (40.1±0.9)%, (35.3±1.6)%, (27.8±2.4)%, respectively ( F = 15.36, P < 0.05); the relative expression level of VEGF protein was (40.3±3.8)%, (35.9±4.6)%, (20.1±2.9)%, respectively ( F = 9.78, P < 0.05). Conclusion:Chidamide and arsenic trioxide have synergistic inhibitory effects on T cell lymphoma Hut-78 cells, which may be related to the down-regulated expressions of bcl-2 and VEGR.

Objective:To explore the clinical efficacy and safety of daratumumab-based combined regimens for relapsed/refractory multiple myeloma (RRMM).Methods:A retrospective case series study was conducted. The clinical data of 38 patients with RRMM in Jining NO.1 People's Hospital from Janunary 2020 to December 2022 were retrospectively analyzed. All patients were treated with daratumumab-based combined regimens. The Dd regimen (12 cases) was treated with daratumumab and dexamethasone, the DPD regimen (20 cases) was treated with pomalodomide based on the Dd regimen, the DVD regimen (6 cases) was treated with bortezomib based on the Dd regimen. The therapeutic efficacy and adverse reactions of all groups were analyzed. Kaplan-Meier method was used for survival analysis.Results:The median follow-up time was 9.5 months (1.0 months, 32.5 months) and the median treatmemt time was 6.2 months (3.2 months, 25.6 months). Among 38 patients, 7 cases (18.7%) achieved complete remission, 9 cases (23.6%) achieved very good partial remission, 10 cases (26.3%) achieved partial remission, 4 cases (10.5%) achieved minimal remission, 5 cases (13.1%) achieved stable disease, 3 cases (7.9%) had the progression of the disease. The overall response rate (ORR) was 78.9% (30/38). The ORR was 66.7%(8/12), 83.3%(5/6), 85.0%(17/20), respectively in the Dd group, DVD group and DPD group. There was no statistically significant difference in the ORR between the DVD group and DPD group ( χ2 = 0.01, P>0.05); there was no statistically significant difference in the ORR between the DVD group and Dd group ( χ2 = 0.55, P>0.05); there was no statistically significant difference in the ORR between the DPD group and Dd group ( χ2 = 1.47, P>0.05). The median progression-free survival (PFS) time was 12.5 months (95% CI: 8.5-24.2 months),the median overall survival (OS) time was not reached, and the 1-year OS rate was 89.4%. Among 38 patients, the main adverse reactions during treatment were infusion-related adverse reactions in 5 cases, grade 3 neutropenia in 7 cases, grade 3 thrombocytopenia in 9 cases, severe anemia in 12 cases; no one had drug discontinuation or drug reduction due to the intolerance of adverse reactions. Conclusions:Daratumumab-based combined regimens in the treatment of RRMM show a favorable efficacy and safety.

Objective:To explore the clinical effect and safety of venetoclax combined with azacitidine for high-risk myelodysplastic syndromes (MDS).Methods:A retrospective case series study was conducted. The clinical data of 48 patients with high-risk MDS in Jining No.1 People's Hospital from January 2020 to May 2023 were collected, and all patients were divided into the control group (20 cases) and the test group (28 cases) according to medications. The control group was treated with azacitidine alone, and the test group was treated with venetoclax combined with azacitidine regimen. The total effective rate and adverse reactions of the 2 groups were compared after 3 courses of treatment.Results:Among 48 patients, 30 cases were male and 18 cases were females; the median onset age [ M ( Q1, Q3)] was 62 years (54 years, 75 years). There were no statistically significant differences in gender, age, white blood cell count, neutrophil count, hemoglobin, platelet count, bone marrow original cells proportion between the 2 groups (all P>0.05). After 3 courses of treatment, the total effective rate in the test group was 75% (22/28), and the rate in the control group was 45% (9/20), and there was a statistically significant difference between the two groups ( χ2 = 5.74, P<0.05). The incidence of grade 3 and the above adverse reactions in the control group and the test group was 25% (5/20), 54% (15/28), respectively, and the difference was statistically significant ( χ2 = 1.62, P>0.05). Conclusions:Venetoclax combined with azacitidine regimen for high-risk MDS can improve the clinical efficacy, and the adverse reactions can be tolerated.

Cell Differentiation ; Cell Line, Tumor ; Cell Proliferation ; Humans ; Interferon-alpha ; Leukemia, Promyelocytic, Acute ; Tretinoin