The relationship between expression of PD-L1 and HIF-1α in glioma cells under hypoxia.

Hypoxia inducible factor-1α (HIF-1α) up-regulates the expression of programmed death ligand-1 (PD-L1) in some extracranial malignancies. However, whether it could increase PD-L1 expression in intracranial tumor is still unknown. Here, we explored the relationship between HIF-1α and PD-L1 expression in glioma, and investigated their clinical significance. In glioma patients, HIF-1α and PD-L1 were overexpressed in high grade glioma tissues and were significantly associated with poor survival. In glioma cells, PD-L1 expression was induced under hypoxia condition, and the enhanced PD-L1 expression was abrogated by either HIF-1α knock-down or HIF-1α inhibitor treatment. Furthermore, ChIP-qPCR analysis showed the direct binding of HIF-1α to PD-L1 proximal promoter region, providing evidence that HIF-1α up-regulates PD-L1 in glioma. In glioma murine model, the combination treatment with HIF-1α inhibitor and anti-PD-L1 antibody caused a more pronounced suppressive effect on tumor growth compared to either monotherapy. Immunologically, the combination treatment improved both dendritic cell (DC) and CD8+ T cell activation. Overall, our results demonstrated that positive correlation between PD-L1 and HIF-1α in glioma, and provide an alternative strategy, inhibiting HIF-1α, as combination therapies with immunotherapies to advance glioma treatment.

Clinical and pathological analysis of 116 cases of adult adrenal cortical adenoma and literature review.

BACKGROUND: The aim of this study is to investigate origin, gross features, microscopic features, immunohistochemical properties, and differential diagnosis of adrenal cortical adenoma (ACA) in patients ≥20 years old. METHODS: The clinicopathological features of 116 cases of ACA and the immunohistochemical features of 50 cases of ACA were evaluated, and the relevant literature was reviewed. RESULTS: In our cohort, 76.72% (89/116) of the cases were functional, and 27 cases had non-functional, benign adrenal adenomas. ACA presented as an island tumor with an envelope, and the mean tumor size was 3.6 cm (range 1-5 cm), with a mean tumor weight of 9.28 g (range 5-113 g). The shape of the tumor cells was consistent, and mitosis was rarely observed. Forty of the 46 patients with cortisol-secreting ACA had tumors containing granule cells. Primary aldosteronism was observed in 43 cases. Thirty-eight cases had endoscopically visible tumors, with clear cells and lipid-rich cytoplasm arranged in irregular patches or strips. Cortisol-producing ACAs were associated with atrophy of the non-tumorous cortex. Adrenocortical adenomas displayed positive immunohistochemical staining for MELAN-A, Syn (46 of 50 cases of ACA), NSE (44 of 50 cases of ACA), Vim (42 of 50 cases of ACA) and Ki-67 <5% (24 of 50 cases of ACA; the remaining 26 cases were negative for Ki-67). CONCLUSION: Prediction of endocrine syndrome in functional ACA was possible based on its structure and morphologic features, which could prevent an unanticipated postoperative crisis. However, a clinical study is needed to validate these findings.

Expression of interleukin-17A in lung tissues of irradiated mice and the influence of dexamethasone.

PURPOSE: To investigate the expressions of IL-17A in different phases of radiation-induced lung injury and the effect of dexamethasone. METHODS: The thorax of C57BL/6 mice was irradiated with 15 Gy rays. Mice from dexamethasone-treated group were injected intraperitoneally with dexamethasone (0.42 mg/kg/day) every day for the first month after irradiation. IL-17A in lung tissues was detected by immunohistochemistry. IL-17A, TGF-ß1, and IL-6 in bronchoalveolar lavage fluid were detected by ELISA. Lung inflammation and collagen deposition were observed by H&E and Masson methods. The degree of alveolitis and fibrosis was judged according to scoring. RESULTS: IL-17A expression was appreciable at 1 week, peaked at 4 weeks, and subsequently declined at 8 weeks after irradiation. IL-17A was reduced after dexamethasone application at all the observation periods. Dexamethasone also inhibited expressions of TGF-ß, IL-6, and TNF-α in bronchoalveolar lavage fluid. Moreover, dexamethasone attenuated the severity of lung injury by reducing the infiltration of inflammatory cells and collagen deposition. Terms of survival and the time of death in mice of treatment group were postponed and survival rate was improved. CONCLUSIONS: IL-17A plays an important role in the process of radiation-induced lung injury. And dexamethasone may provide a protective role in lung injury induced by radiation.

Interleukin-17A antagonist attenuates radiation-induced lung injuries in mice.

OBJECTIVE: To investigate the effect of interleukin-17A (IL-17A) antibodies on radiation-induced lung injuries in mice. METHODS: The thorax of 135 mice were divided into Sham (n = 30), radiation control (RC, n = 35), treatment (n = 35, IL-17A-neutralizing antibody, 4 µg/mouse, IV, 4 days per month for 4 months) and placebo group (n = 35) before a single dose irradiation (15 Gy) to the thorax. Inflammation and collagen contents in the lung tissues were examined, and the concentration of IL-17A, TGF-ß1, and IL-6 in bronchoalveolar lavage fluid (BALF) were measured. In another 50 animals, 180-day survival rate following the irradiation and treatment was calculated by Kaplan-Meier method. RESULTS: Sixteen weeks after the irradiation and treatment, there was significant inflammatory cell infiltration and interstitial collagen depositions in the radiation control and placebo groups, whereas these changes were relatively mild in the treatment group. The percentage of grade II and III alveolitis in the treatment group (16%, P < .05) was lower than in the RC (72%) or placebo group (64%). The mean Aschcroft fibrosis scores were 2.8 (treatment group), 5.2 (RC), and 4.8 (placebo group), respectively. The scores of treatment group was lower than that of RC (P < .001) or placebo group (P < .001). The IL-17A, TGF-ß, and IL-6 concentrations in the treatment group were lower than in the RC and placebo group (P < .01) following the irradiation. The 180-day mortality rate in the treatment group was lower than in the RC group 16.7% versus 75.0%, P < .05). CONCLUSION: IL-17A antibody treatment alleviates radiation-induced pneumonitis and subsequent fibrosis, and improvise postirradiation survival.

[Early high-volume hemofiltration treatment in severe sepsis].

OBJECTIVE: To evaluate the effect of early application of high-volume hemofiltration treatment (HVHF) on the levels of lactic acid, pro-inflammatory cytokines and C-reactive protein (CRP) in plasma, as well as APACHE II score in patients suffering from severe sepsis. METHODS: Thirty patients meeting the diagnosis of severe sepsis were enrolled in the trial within 24 hours of insults. The level of lactic acid, interleukin-6 (IL-6) and CRP in plasma were measured before HVHF and at 24, 48 or 72 h following HVHF treatment. RESULT: The plasma levels of lactic acid and IL-6 decreased significantly at 24 h, 48 h, 72 h after HVHF (P <0.05), while, IL-10 did not differ significantly following HVHF (P>0.05), when compared with that before HVHF. CONCLUSION: The early application of HVHF could clear the plasma lactic acid and pro-inflammatory cytokines, and improve the tissue oxygenation in severe sepsis.

Impact of acute pulmonary embolism on plasma and tissue hepatocyte growth factor: an experimental study.

This study was designed to investigate the impact of acute pulmonary embolism (PE) on plasma and tissue hepatocyte growth factor (HGF). PE was established in 16 New Zealand white rabbits by intravenous injection of autologous blood clots. Another 16 sham-operated rabbits were used as control. Plasma HGF levels and tissue HGF expression was measured by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry, respectively. The plasma HGF levels in the PE group were elevated 1 hour after PE (P < .01). In the lung tissue samples, the positive HGF expression ratio was 91.7% and 20.8%, respectively, in the PE and the control group (P < .01). The positive HGF expression ratio in the right ventricular tissue samples in the PE group was higher than in the control group (75.0% versus 20.9%; P < .01). The positive HGF expression ratio in the liver samples in the PE and the control groups was 33.3% and 16.7%, respectively (P < .05). In conclusion, acute PE was associated with a significant increase in plasma HGF. Acute PE was also associated with an enhanced HGF expression in the lungs, the right ventricle, and the liver.