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ABSTRACT Objective To determine the role of the AKT pathway in the regulating of natural Killer-induced apoptosis of acute myeloid leukemia cells and to characterize the associated molecular mechanisms. Methods BALB/c nude mice were injected with HL60 cells to induce a xenogenic model of subcutaneous leukemic tumors. Mice were treated with perifosine, and their spleens were analyzed using biometry, histopathology, and immunohistochemistry. Gene expression analysis in leukemia cells was performed by real-time PCR. Protein analysis of leukemia and natural Killer cells was performed by flow cytometry. AKT inhibition in HL60 cells, followed by co-culture with natural Killer cells was performed to assess cytotoxicity. Apoptosis rate was quantified using flow cytometry. Results Perifosine treatment caused a reduction in leukemic infiltration in the spleens of BALB/c nude mice. In vitro , AKT inhibition reduced HL60 resistance to natural Killer-induced apoptosis. AKT inhibition suppressed the immune checkpoint proteins PD-L1, galectin-9, and CD122 in HL60 cells, but did not change the expression of their co-receptors PD1, Tim3, and CD96 on the natural Killer cell surface. In addition, the death receptors DR4, TNFR1, and FAS were overexpressed by AKT inhibition, thus increasing the susceptibility of HL60 cells to the extrinsic pathway of apoptosis. Conclusion The AKT pathway is involved in resistance to natural Killer-induced apoptosis in HL60 cells by regulating the expression of immune suppressor receptors. These findings highlight the importance of AKT in contributing to immune evasion mechanisms in acute myeloid leukemia and suggests the potential of AKT inhibition as an adjunct to immunotherapy.
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Purpose: To study the impact of moderate and severe primary open?angle glaucoma (POAG) on the quality of life (QoL) due to activity limitation using glaucoma?specific questionnaires. Methods: This cross?sectional study enrolled 122 participants, 50% (n = 61) being controls and 50% were diagnosed cases of moderate/ severe POAG. Three orally administered glaucoma?specific QoL instruments were used: Glaucoma Activity Limitation (GAL?9), Glaucoma Quality of Life (GQL?15), and Viswanathan questionnaires. The questions related to activity limitation were identified and analyzed for each questionnaire separately. Results: The mean age of the participants was 61.04 ± 9.88 years and a majority were males (64.8%, n = 79). The mean scores in controls, moderate glaucoma, and severe POAG patients for GAL?9 questionnaire were 9.77 ± 1.36 (P = 0.44), 13.75 ± 4.76 (P < 0.001), and 23.45 ± 5.62 (P < 0.001), for GQL?15, these were 16.39 ± 2.18 (P = 0.5), 22.75 ± 7.89 (P < 0.001), and 39.34 ± 9.42 (P < 0.001), respectively, while for the Viswanathan questionnaire, they were 9.49 ± 0.94 (P = 0.38), 7.91 ± 1.59 (P < 0.001), and 4.41 ± 2.20 (P < 0.001), respectively. The GQL?15 and GAL?9 questionnaires concluded that activity limitation pertaining to dark adaptation?related tasks affected the QoL the most in moderate as well as severe POAG (P < 0.001). Using the Viswanathan questionnaire, it was observed that the peripheral vision?related activity limitation was most significant for the decrease in QoL in moderate POAG while near vision?related activity limitation affected the QoL the most in severe POAG (P < 0.001). Conclusion: All three questionnaires concluded that the activity limitation due to moderate and severe glaucoma has a negative impact on the QoL. The limitation of the tasks involving dark adaptation/glare and peripheral vision has the most significant impact on the QoL in moderate glaucoma. As the disease progresses to a severe category, the limitation of activities requiring central and near vision causes the most significant worsening in QoL.
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Objective • To detect T cell immunoglobulin mucin 3 (Tim-3) and galectin 9 (Gal-9) expression as well as CD3+ T cells and CD8+ T cells infiltration in the tumor tissues of adenocarcinoma of the esophagogastric junction (AEG), and analyze their correlations with the patients' clinical characteristics and survival prognosis. Methods • A retrospective case study was used to collect clinical data and follow-up data of 116 AEG patients who were admitted to Renji Hospital, Shanghai Jiao Tong University School of Medicine from Dec. 2005 to Dec. 2013. Tim-3, Gal-9, CD3, and CD8 protein expressions were detected by immunohistochemistry in the tumor tissues, and the clinical characteristics and prognosis were compared among the patients with different levels of protein expression and T cells infiltration. Results • The results of immunohistochemistry showed that Tim-3 mainly expressed in the infiltrating immune cells, and Gal-9 mainly expressed in the tumor cells. The analysis on the clinical characteristics revealed that Tim-3 expression level was related to the Siewert classification (P=0.030) and CD8+ T cells infiltration level was related to the tumor TNM stage (P=0.042). The results of survival analysis showed that the patients with high level of CD8+ T cells infiltration had a better survival prognosis (P=0.047). However, there was no difference in the prognosis among the patients with different Tim-3 and/or Gal-9 expression levels or with different CD3+ T cell infiltration levels. Conclusion • AEG patients with high level of CD8+ T cells infiltration usually have earlier TNM stages and better prognosis. There is no significant difference in the prognosis of AEG patients with different Tim-3/Gal-9 expression levels.
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Objective To investigate and analyze the expression of serum NO and Gal-9and its correlation with apoptosis in elderly patients with cervical cancer.Methods 76cases of elderly patients with cervical cancer in our hospital as the cervical cancer group, 50cases of cervical epithelial dysplasia of uterus in elderly (CIN) were taken as CIN group and 50healthy elderly people as healthy controls were detected by flow cytometry in three subjects tissue apoptosis index (AI) and the detection of serum NO and Gal-9levels in three groups of subjects, difference analysis and correlation of the indicators of the three groups of subjects, and analyze the relationship between the serum of patients with cervical cancer NO, Gal-9levels and pathological features.Results There was a significant difference in the tissue apoptosis index (AI) between the three groups (P<0.05) , and the AIindex in the cervical cancer group was significantly higher than that in the healthy control group (P<0.05) , but it was significantly lower than that in the CIN group (P<0.05) .The serum NO and Gal-9levels of the three groups were statistically different (P<0.05) , and the levels of NO and Gal-9in the cervical cancer group were significantly higher than those in the healthy control group and CIN group (P<0.05) .The serum levels of NO and Gal-9in patients with cervical cancer were positively correlated with the value of AI (r=0.813, 0.872, P<0.05) .The serum NO and Gal-9levels in patients with stageⅢandⅣof cervical cancer were significantly higher than those inⅠandⅡpatients (P<0.05) .The serum Gal-9level in patients with poorly differentiated tumors was significantly higher than that in patients with high or intermediate differentiation (P<0.05) .Conclusion Serum NO and Gal-9play an important role in the occurrence and development of cervical cancer in elderly patients, and play a certain role in the apoptosis of cervical cancer tissues.The specific mechanisms of their effects need further research and analysis.