ABSTRACT
Objective: To explore the composition of ascites lymphocytes in high-grade serous ovarian carcinoma (HGSOC) and its correlation with clinical features. Methods: A total of 59 newly-diagnosed HGSOC patients, aged (58±11) years old, who were treated at the Department of Obstetrics and Gynecology of Peking University Third Hospital from July 2019 to December 2020 were included, collecting ascites and peritoneal irrigation fluid respectively. Detect the proportion of T, B, NK cell and its subpopulations by flow cytometry, and analyze its correlation with the clinical characteristics of patients. Results: Among 59 patients, 48 patients (81.4%) had ascites, and 11 patients (18.6%) had no ascites. Compared with the peritoneal irrigation fluid, the CD3+T (70.2%±15.6% vs 78.1%±6.7%, P=0.014), CD8+T (38.3%±11.2% vs 47.7%±10.1%, P=0.014) and CD16-CD56bright NK [2.0% (0.8%, 3.6%) vs 4.2% (1.5%, 7.1%), P=0.026] cells were significantly decreased in the ascites, while the CD16+CD56dim NK cells was significantly increased [6.8% (2.8%, 15.7%) vs 2.6% (1.6%, 4.3%), P=0.008]. In patients with ascites volume ≥1 000 ml, CD16-CD56bright NK cells were significantly increased than those ascites volume<1 000 ml [3.1% (1.2%, 3.9%) vs 0.8% (0.4%, 2.3%), P=0.002]. Age was significantly positively correlated with the level of CD4+T cells (r=0.332, P=0.021) and the ratio of CD4+T/CD8+T (r=0.379, P=0.008) in ascites. In ascites from patients with poor response to treatment, the proportion of CD4+T cells was increased significantly than those with better response (64.7%±4.2% vs 48.3%±11.7%, P=0.002). Conclusion: The formation of ascites in newly diagnosed high-grade serous epithelial ovarian cancer patients would affect the lymphocyte composition in the abdominal cavity microenvironment, which is related to the patient's age, cancer progression and treatment response.
Subject(s)
Ascites , Ovarian Neoplasms , Aged , Female , Flow Cytometry , Humans , Killer Cells, Natural , Middle Aged , T-Lymphocytes , Tumor MicroenvironmentABSTRACT
Activin A (Act A), a member of transforming growth factor-ß (TGF-ß) superfamily, is an early gene in response to cerebral ischemia. Growing evidences confirm the neuroprotective effect of Act A in ischemic injury through Act A/Smads signal activation. In this process, regulation networks are involved in modulating the outcomes of Smads signaling. Among these regulators, crosstalk between c-Jun N-terminal kinase (JNK) and Smads signaling has been found in the TGF-ß induced epithelial-mesenchymal transition. However, in neural ischemia, the speculative regulation between JNK and Act A/Smads signaling pathways has not been clarified. To explore this issue, an Oxygen Glucose Deprivation (OGD) model was introduced to nerve-like PC12 cells. We found that JNK signal activation occurred at the early time of OGD injury (1 h). Act A administration suppressed JNK phosphorylation. In addition, JNK inhibition could elevate the strength of Smads signaling and attenuate neural apoptosis after OGD injury. Our results indicated a negative regulation effect of JNK on Smads signaling in ischemic injury. Taken together, JNK, as a critical site for neural apoptosis and negative regulator for Act A/Smads signaling, was presumed to be a molecular therapeutic target for ischemia.
Subject(s)
Activins/pharmacology , Cell Hypoxia , Glucose/pharmacology , JNK Mitogen-Activated Protein Kinases/metabolism , Oxygen/metabolism , Signal Transduction/drug effects , Animals , Anthracenes/pharmacology , Blotting, Western , Cell Differentiation/drug effects , Cell Survival/drug effects , Epithelial-Mesenchymal Transition/drug effects , JNK Mitogen-Activated Protein Kinases/antagonists & inhibitors , Microscopy, Fluorescence , Nerve Growth Factor/pharmacology , PC12 Cells , Phosphorylation/drug effects , Rats , Smad Proteins/metabolism , Transforming Growth Factor beta/pharmacologyABSTRACT
The preventive effect of the extracts of Dunaliella Salina (EDS) on NSAR-induced squamous cell cancer of proventriculus in mice was investigated. Results showed beta-carotene (BC) and DEC could significantly inhibit NSAR-induced carcinogenesis. The greatest inhibition effect was achieved in high-does- EDS group, with an inhibitory rate of 55.6%, but not significantly different from that in BC group (P > 0.05). The proliferation of spleen cells and production of tumour necrosis factor (TNF) by the peritoneal macrophages markedly enhanced in both BC and EDS groups of mice. These findings suggested the prevention of NSAR-induced cancer of proventriculus in mice may be resulted from enhancement of cell immunity.
